Trial Outcomes & Findings for Tacrolimus/Everolimus vs. Tacrolimus/MMF in Pediatric Heart Transplant Recipients Using the MATE Score (NCT NCT03386539)
NCT ID: NCT03386539
Last Updated: 2026-07-31
Results Overview
MATE-3 is a validated score ranging from 0 to 12. The score adds together each subscore so that it represents the cumulative burden of three major adverse transplant events: Cardiac Allograft Vasculopathy (CAV), Chronic Kidney Disease (CKD), and Biopsy-proven Acute Cellular Rejection (ACR). Complete details of the score can be found in the study protocol. A higher score represents a worse outcome.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
211 participants
Primary outcome timeframe
30 months post-randomization
Results posted on
2026-07-31
Participant Flow
Heart transplant recipients who were alive 6 months after their heart transplant procedure were recruited at 25 pediatric heart transplant hospitals in the United States from January 2018 to August 2020.
Participants were assessed for eligibility according to inclusion and exclusion criteria and asked to provide informed consent. All eligible participants were randomized.
Participant milestones
| Measure |
Everolimus/Low-Dose Tacrolimus
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
Tacrolimus/Mycophenolate Mofetil
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
|---|---|---|
|
Overall Study
STARTED
|
107
|
104
|
|
Overall Study
COMPLETED
|
107
|
100
|
|
Overall Study
NOT COMPLETED
|
0
|
4
|
Reasons for withdrawal
| Measure |
Everolimus/Low-Dose Tacrolimus
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
Tacrolimus/Mycophenolate Mofetil
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
3
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
Tacrolimus/Everolimus vs. Tacrolimus/MMF in Pediatric Heart Transplant Recipients Using the MATE Score
Baseline characteristics by cohort
| Measure |
Everolimus/Low-Dose Tacrolimus
n=107 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
Tacrolimus/Mycophenolate Mofetil
n=104 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Total
n=211 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
< 1 year of age
|
22 Participants
n=9 Participants
|
13 Participants
n=27 Participants
|
35 Participants
n=267 Participants
|
|
Age, Customized
1 to < 6 years of age
|
32 Participants
n=9 Participants
|
25 Participants
n=27 Participants
|
57 Participants
n=267 Participants
|
|
Age, Customized
6 to < 12 years of age
|
17 Participants
n=9 Participants
|
24 Participants
n=27 Participants
|
41 Participants
n=267 Participants
|
|
Age, Customized
12 to < 18 years of age
|
35 Participants
n=9 Participants
|
35 Participants
n=27 Participants
|
70 Participants
n=267 Participants
|
|
Age, Customized
Greater than or equal to 18 years of age
|
1 Participants
n=9 Participants
|
7 Participants
n=27 Participants
|
8 Participants
n=267 Participants
|
|
Sex: Female, Male
Female
|
48 Participants
n=9 Participants
|
50 Participants
n=27 Participants
|
98 Participants
n=267 Participants
|
|
Sex: Female, Male
Male
|
59 Participants
n=9 Participants
|
54 Participants
n=27 Participants
|
113 Participants
n=267 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=9 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=267 Participants
|
|
Race (NIH/OMB)
Asian
|
5 Participants
n=9 Participants
|
7 Participants
n=27 Participants
|
12 Participants
n=267 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=9 Participants
|
1 Participants
n=27 Participants
|
1 Participants
n=267 Participants
|
|
Race (NIH/OMB)
Black or African American
|
12 Participants
n=9 Participants
|
8 Participants
n=27 Participants
|
20 Participants
n=267 Participants
|
|
Race (NIH/OMB)
White
|
84 Participants
n=9 Participants
|
84 Participants
n=27 Participants
|
168 Participants
n=267 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=9 Participants
|
0 Participants
n=27 Participants
|
2 Participants
n=267 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=9 Participants
|
4 Participants
n=27 Participants
|
8 Participants
n=267 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
23 Participants
n=9 Participants
|
29 Participants
n=27 Participants
|
52 Participants
n=267 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
83 Participants
n=9 Participants
|
72 Participants
n=27 Participants
|
155 Participants
n=267 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=9 Participants
|
3 Participants
n=27 Participants
|
4 Participants
n=267 Participants
|
|
Chronic kidney disease stage
Stage 1/2
|
106 Participants
n=9 Participants
|
101 Participants
n=27 Participants
|
207 Participants
n=267 Participants
|
|
Chronic kidney disease stage
Stage 3A
|
1 Participants
n=9 Participants
|
3 Participants
n=27 Participants
|
4 Participants
n=267 Participants
|
|
Chronic kidney disease stage
Stage 3B
|
0 Participants
n=9 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=267 Participants
|
|
Chronic kidney disease stage
Stage 4/5
|
0 Participants
n=9 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=267 Participants
|
PRIMARY outcome
Timeframe: 30 months post-randomizationPopulation: Intention to treat population; participants who were lost to follow-up or withdrew consent had their last MATE 3 score carried forward.
MATE-3 is a validated score ranging from 0 to 12. The score adds together each subscore so that it represents the cumulative burden of three major adverse transplant events: Cardiac Allograft Vasculopathy (CAV), Chronic Kidney Disease (CKD), and Biopsy-proven Acute Cellular Rejection (ACR). Complete details of the score can be found in the study protocol. A higher score represents a worse outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=104 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=107 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
EFFICACY: MATE-3 Score
|
1.3 Scores on a scale
Standard Deviation 2.5
|
0.9 Scores on a scale
Standard Deviation 2.2
|
PRIMARY outcome
Timeframe: 30 months post-randomizationPopulation: Intention to treat population; participants who were lost to follow-up or withdrew consent had their last MATE-6 score carried forward.
MATE-6 is a validated score ranging from 0 to 24. The score adds together each subscore so that it represents the cumulative burden of all six major adverse transplant events: Coronary Artery Vasculopathy (CAV), Chronic Kidney Disease (CKD), Biopsy-proven Acute Cellular Rejection (ACR), pathologic diagnosis of Antibody-Mediated Rejection (AMR), Infection, and Post-Transplant Lymphoproliferative Disorder (PTLD). Complete details of the score can be found in the study protocol. A higher score represents a worse outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=104 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=107 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
SAFETY: MATE-6 Score
|
2.4 Scores on a scale
Standard Deviation 5.2
|
2.0 Scores on a scale
Standard Deviation 4.6
|
SECONDARY outcome
Timeframe: Up to 30 months post-randomizationPopulation: Intention to treat, censored at lost to follow-up or withdrawal of consent
Number of participants who experienced death from any cause
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=104 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=107 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Efficacy: Overall Patient Survival
|
3 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: Up to 30 months post-randomizationPopulation: Intention to treat, censored at lost to follow-up or withdrawal of consent
Number of participants who experienced death or heart re-transplantation
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=104 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=107 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Efficacy: Overall Allograft Survival
|
5 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: 0 to 6 months, 0 to 12 months, 0 to 30 months post-randomizationPopulation: All patients with paired eGFR estimates at specified timepoints
Change in estimated glomerular filtration rate (eGFR) using the modified Schwartz equation. A positive number indicates improved kidney function, a negative number indicates worsened kidney function.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=104 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=107 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Efficacy: Change in Kidney Function
Change from baseline to 30 months post-randomization
|
5.2 ml/min/1.73 m^2
Standard Deviation 37.4
|
8.6 ml/min/1.73 m^2
Standard Deviation 32.3
|
|
Efficacy: Change in Kidney Function
Change from baseline to 6 months post-randomization
|
11.9 ml/min/1.73 m^2
Standard Deviation 31.1
|
20.5 ml/min/1.73 m^2
Standard Deviation 32.7
|
|
Efficacy: Change in Kidney Function
Change from baseline to 12 months post-randomization
|
4.9 ml/min/1.73 m^2
Standard Deviation 32.7
|
15.4 ml/min/1.73 m^2
Standard Deviation 35.2
|
SECONDARY outcome
Timeframe: From enrollment to 30 months after enrollmentPopulation: Intention to treat, censored at lost to follow-up or withdrawal of consent
Number of participants who are "free from" (have NOT experienced) a chronic kidney disease MATE. A chronic kidney disease MATE was defined as an eGFR \< 60 ml/min/1.73 m\^2 during follow-up or worsening by at least one MATE score if \< 60 ml/min/1.73 m\^2 at baseline. A higher number of participants on this measure indicates a better outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=104 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=107 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Efficacy: Freedom From CKD Event
|
99 Participants
|
105 Participants
|
SECONDARY outcome
Timeframe: From enrollment to 30 months after enrollmentPopulation: Intention to treat, censored at lost to follow-up or withdrawal of consent
Number of participants who are "free from" (have NOT experienced) cardiac allograft vasculopathy (CAV) during follow up as graded by the angiography core laboratory. A higher number of participants on this measure indicates a better outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=104 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=107 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Efficacy: Freedom From CAV Event
|
73 Participants
|
80 Participants
|
SECONDARY outcome
Timeframe: From enrollment to 30 months after enrollmentPopulation: Intention to treat, censored at lost to follow-up or withdrawal of consent
Number of participants who are "free from" (have NOT experienced) biopsy-proven Acute Cellular Rejection (ACR) MATE event during follow-up. A higher number of participants on this measure indicates a better outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=104 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=107 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Efficacy: Freedom From BP-ACR Event
|
89 Participants
|
92 Participants
|
SECONDARY outcome
Timeframe: From enrollment to 30 months after enrollmentPopulation: Intention to treat, censored at lost to follow-up or withdrawal of consent
Number of participants who are "free from" (have NOT experienced) the composite of death, graft loss, 2R/3R acute cellular rejection or rejection with hemodynamic compromise. A higher number of participants on this measure indicates a better outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=104 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=107 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Efficacy: Freedom From Composite Failure
|
85 Participants
|
94 Participants
|
SECONDARY outcome
Timeframe: 30 months post-randomizationPopulation: Completed by study participant. Participant must be ≥ 8 years and able to complete the EQ-5D-Y at 30 month post-randomization study visit. A higher score represents a better outcome.
The EuroQOL EQ-5D Y uses a visual-analog scale and asks the participant to mark an X on the line to show how good or bad your is health TODAY. The scale ranges from 0 to 100.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=45 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=33 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Efficacy: EuroQOL EQ-5D Y (Youth Version)
|
90.0 Scores on a scale
Standard Deviation 12.3
|
91.5 Scores on a scale
Standard Deviation 14.6
|
SECONDARY outcome
Timeframe: From enrollment to 30 months after enrollmentPopulation: Intention to treat, censored at lost to follow-up or withdrawal of consent
Number of participants who are "free from" (have NOT experienced) a pathologic diagnosis of Antibody-Mediated Rejection (AMR) MATE Event. A higher number of participants on this measure indicates a better outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=104 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=107 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Safety: Freedom From AMR
|
98 Participants
|
103 Participants
|
SECONDARY outcome
Timeframe: From enrollment to 30 months after enrollmentPopulation: Intention to treat, censored at lost to follow-up or withdrawal of consent
Number of participants who are "free from" (have NOT experienced) a serious infection MATE during follow-up. A higher number of participants on this measure indicates a better outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=104 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=107 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Safety: Freedom From Infection
|
82 Participants
|
80 Participants
|
SECONDARY outcome
Timeframe: From enrollment to 30 months after enrollmentPopulation: Intention to treat, censored at lost to follow-up or withdrawal of consent
Number of participants who are "free from" (have NOT experienced) a Post-Transplant Lymphoproliferative Disorder (PTLD) MATE event during follow-up. A higher number of participants on this measure indicates a better outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=104 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=107 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Safety: Freedom From PTLD
|
103 Participants
|
105 Participants
|
SECONDARY outcome
Timeframe: From enrollment to 30 months after enrollmentPopulation: All participants who were randomized are included in this population.
Adverse events reported throughout the study. Adverse events are classified by CTCAE classification. Serious adverse events include CTCAE classes 3, 4, and 5.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=104 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=107 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Safety: Number of Participants Experiencing Adverse Events
Any adverse event
|
99 Participants
|
103 Participants
|
|
Safety: Number of Participants Experiencing Adverse Events
Serious adverse events
|
59 Participants
|
75 Participants
|
SECONDARY outcome
Timeframe: From enrollment to 30 months after enrollmentPopulation: Intention to treat, censored at lost to follow-up or withdrawal of consent
Number of participants who are "free from" (have NOT experienced) any MATE event, this includes chronic kidney disease, cardiac allograft vasculopathy, acute cellular rejection, antibody mediated rejection, serious infection, and post-transplant lymphoproliferative disease. A higher number of participants on this measure indicates a better outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=104 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=107 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Safety: Freedom From Major Transplant Events (Composite)
|
45 Participants
|
52 Participants
|
SECONDARY outcome
Timeframe: From enrollment to 30 months after enrollmentPopulation: Intention to treat, censored at lost to follow-up or withdrawal of consent
Number of participants who are "free from" (have NOT experienced) a chronic kidney disease MATE of Grade 2 or greater (eGFR \<45 ml/min/1.73 m\^2 or on dialysis) or death due to chronic kidney disease. A higher number of participants on this measure indicates a better outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=104 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=107 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Safety: Freedom From Grade 2 or Greater Severity CKD Event
|
104 Participants
|
106 Participants
|
SECONDARY outcome
Timeframe: From enrollment to 30 months after enrollmentPopulation: Intention to treat, censored at lost to follow-up or withdrawal of consent
Number of participants who are "free from" (have NOT experienced) a cardiac allograft vasculopathy MATE of Grade 2 or greater. Grade 2 or greater is the same as having International Society of Heart and Lung Transplantation cardiac allograft vasculopathy Grade 2 or 3 or death due to cardiac allograft vasculopathy. A higher number of participants on this measure indicates a better outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=104 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=107 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Safety: Freedom From Grade 2 or Greater Severity CAV Event
|
90 Participants
|
98 Participants
|
SECONDARY outcome
Timeframe: From enrollment to 30 months after enrollmentPopulation: Intention to treat, censored at lost to follow-up or withdrawal of consent
Number of participants who are "free from" (have NOT experienced) an acute cellular rejection MATE of Grade 2 or greater. Grade 2 or greater is the equivalent of treated rejection with an assigned International Society of Heart \& Lung Transplantation acute cellular rejection grade 2 or grade 3 or rejection with hemodynamic compromise (decreased ejection fraction, need for IV medicine to support heart, need for mechanical circulatory support) or death due to acute cellular rejection. A higher number of participants on this measure indicates a better outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=104 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=107 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Safety: Freedom From Grade 2 or Greater Severity ACR Event
|
89 Participants
|
95 Participants
|
SECONDARY outcome
Timeframe: From enrollment to 30 months after enrollmentPopulation: Intention to treat, censored at lost to follow-up or withdrawal of consent
Number of participants who are "free from" (have NOT experienced) an antibody mediated rejection MATE of Grade 2 or greater. Grade 2 or greater is the equivalent of treated rejection with an assigned International Society of Heart \& Lung Transplantation antibody mediated rejection grade 2 or grade 3 or antibody mediated rejection with hemodynamic compromise (decreased ejection fraction, need for IV medicine to support heart, need for mechanical circulatory support) or death due to antibody mediated rejection. A higher number of participants on this measure indicates a better outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=104 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=107 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Safety: Freedom From Grade 2 or Greater Severity AMR Event
|
98 Participants
|
103 Participants
|
SECONDARY outcome
Timeframe: From enrollment to 30 months after enrollmentPopulation: Intention to treat, censored at lost to follow-up or withdrawal of consent
Number of participants who are "free from" (have NOT experienced) a serious infection MATE of Grade 2 or greater. Grade 2 infections require treatment with intravenous antibiotics or antivirals for 5 or more days. Grade 3 includes treatment of sepsis, endocarditis, invasive infection, or infection leading to respiratory failure. Grade 4 is death due to infection. A higher number of participants on this measure indicates a better outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=104 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=107 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Safety: Freedom From Grade 2 or Greater Severity Infection Event
|
97 Participants
|
94 Participants
|
SECONDARY outcome
Timeframe: From enrollment to 30 months after enrollmentPopulation: Intention to treat, censored at lost to follow-up or withdrawal of consent
Number of participants who are "free from" (have NOT experienced) a post-transplant lymphoproliferative disease MATE of Grade 2 or greater. A higher number of participants on this measure indicates a better outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=104 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=107 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Safety: Freedom From Grade 2 or Greater Severity PTLD Event
|
103 Participants
|
105 Participants
|
SECONDARY outcome
Timeframe: From enrollment to 30 months after enrollmentPopulation: Intention to treat, censored at lost to follow-up or withdrawal of consent
Number of participants who are "free from" (have NOT experienced) at least one of cardiac allograft vasculopathy, chronic kidney disease with estimated glomerular filtration rate less than or equal to 60 ml/min/1.73m2, treated acute cellular rejection, or any cytomegalovirus infection. A higher number of participants on this measure indicates a better outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=104 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=107 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Efficacy: Freedom From Composite of CAV, CKD, BP-ACR, or Any CMV Infection
|
43 Participants
|
59 Participants
|
SECONDARY outcome
Timeframe: Baseline visit through 30 months post-randomizationPopulation: Participants had to have assessments at baseline and 30 months post-randomization. 1 patient had acute kidney injury at baseline and was excluded from this analysis. The remainder did not have assessments at 30 months post-randomization.
Change in chronic kidney disease stage where improvements in CKD stage can take on a negative value.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=88 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=100 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Efficacy: Change in CKD Stage
-2 (Improvement by 2 CKD Stages)
|
1 Participants
|
1 Participants
|
|
Efficacy: Change in CKD Stage
-1 (Improvement by 1 CKD Stage)
|
15 Participants
|
12 Participants
|
|
Efficacy: Change in CKD Stage
0 (No change in CKD Stage)
|
64 Participants
|
78 Participants
|
|
Efficacy: Change in CKD Stage
1 (Worsening by 1 CKD Stage)
|
8 Participants
|
9 Participants
|
SECONDARY outcome
Timeframe: Baseline visit through 30 months post-randomizationPopulation: Intention to treat population; participants who were lost to follow-up or withdrew consent had their last score carried forward. One participant with a missing kidney function assessment at baseline was imputed based on the 6-month post-randomization assessment.
MATE-3 is a validated score ranging from 0 to 12. The score adds together each subscore so that it represents the cumulative burden of three major adverse transplant events: Cardiac Allograft Vasculopathy (CAV), Chronic Kidney Disease (CKD), and Biopsy-proven Acute Cellular Rejection (ACR). For this version of the score, the chronic kidney disease score is replaced by the change in MATE-CKD score from baseline visit through 30 months post-randomization. CKD change score can assume a negative value. This modified score can range from -2 to 12. A higher score represents a worse outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=104 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=107 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Efficacy: MATE-3 Score Where CKD Score is Calculated by Change From Baseline Visit
|
1.17 Points
Standard Deviation 2.49
|
0.89 Points
Standard Deviation 2.16
|
SECONDARY outcome
Timeframe: Baseline visit through 30 months post-randomizationPopulation: Intention to treat population; participants who were lost to follow-up or withdrew consent had their last score carried forward. One participant with a missing kidney function assessment at baseline was imputed based on the 6-month post-randomization assessment.
MATE-3 is a validated score ranging from 0 to 12. The score adds together each subscore so that it represents the cumulative burden of three major adverse transplant events: Cardiac Allograft Vasculopathy (CAV), Chronic Kidney Disease (CKD), and Biopsy-proven Acute Cellular Rejection (ACR). For this version of the score, the chronic kidney disease score is replaced by the change in chronic kidney disease stage from the baseline visit through 30 months post-randomization. Chronic kidney disease stage change score can assume a negative value. This modified score can range from -2 to 12. A higher score represents a worse outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=104 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=107 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Efficacy: MATE-3 Score Where CKD Score is Replaced by Change in CKD Stage
|
1.10 Points
Standard Deviation 2.56
|
0.84 Points
Standard Deviation 2.22
|
SECONDARY outcome
Timeframe: Baseline visit through 30 months post-randomizationPopulation: Intention to treat population; participants who were lost to follow-up or withdrew consent have their last score carried forward.
Composite score ranging from 0 to 16. The score adds each subscore to represent the cumulative burden of three major adverse transplant events plus CMV infection. The three major adverse transplant events are Cardiac Allograft Vasculopathy (CAV), Chronic Kidney Disease (CKD), and Biopsy-proven Acute Cellular Rejection (ACR). Any CMV infection is assigned a score of 1 with additional points using the MATE infection scoring criteria. Full details of the score can be found in the protocol. A higher score represents a worse outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=104 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=107 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Efficacy: Composite Score Consisting of MATE CAV, MATE BP-ACR, MATE CKD Score, and Any CMV Infection.
|
1.51 Scores on a scale
Standard Deviation 2.46
|
1.06 Scores on a scale
Standard Deviation 2.17
|
SECONDARY outcome
Timeframe: Baseline visit through 30 months post-randomizationPopulation: Intention to treat population; participants who were lost to follow-up or withdrew consent have their last score carried forward. One patient had imputation of the baseline CKD stage using the month 6 post-randomization value.
Composite score ranging from -2 to 16. The score adds each subscore to represent the cumulative burden of Cardiac Allograft Vasculopathy (CAV), chronic kidney disease, and Biopsy-proven Acute Cellular Rejection (ACR). Any CMV infection is assigned a score of 1 with additional points using the MATE infection scoring criteria. The chronic kidney disease MATE score is replaced by change in CKD stage. A higher score represents a worse outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=104 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=107 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Efficacy: Composite Score Consisting of MATE CAV, MATE BP-ACR, Change in CKD Stage, and Any CMV Infection.
|
1.36 Scores on a scale
Standard Deviation 2.55
|
0.97 Scores on a scale
Standard Deviation 2.21
|
SECONDARY outcome
Timeframe: BaselinePopulation: Scores were assigned at baseline, 18-months post-randomization, and 30-months post-randomization. Reasons for missing scores include lost to follow-up and clinicians not assigning scores at each visit.
Validated functional performance score, assigned by clinician assessment: Lansky score is assigned if \< 16 years old at randomization. Each score is on a 10-100 point scale and is assigned in 10-point increments (i.e. 10, 20, 30, etc.). A higher score represents a better outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=92 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=98 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Efficacy: Lansky Scores
|
92.45 Scores on a scale
Standard Deviation 10.12
|
93.83 Scores on a scale
Standard Deviation 10.12
|
SECONDARY outcome
Timeframe: 18 months post-randomizationPopulation: Scores were assigned at baseline, 18-months post-randomization, and 30-months post-randomization. Reasons for missing scores include lost to follow-up and clinicians not assigning scores at each visit.
Validated functional performance score, assigned by clinician assessment: Lansky score is assigned if \< 16 years old at randomization. Each score is on a 10-100 point scale and is assigned in 10-point increments (i.e. 10, 20, 30, etc.). A higher score represents a better outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=87 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=96 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Efficacy: Lansky Scores
|
94.77 Scores on a scale
Standard Deviation 7.99
|
95.42 Scores on a scale
Standard Deviation 8.45
|
SECONDARY outcome
Timeframe: 30 months post-randomizationPopulation: Scores were assigned at baseline, 18-months post-randomization, and 30-months post-randomization. Reasons for missing scores include lost to follow-up and clinicians not assigning scores at each visit.
Validated functional performance score, assigned by clinician assessment: Lansky score is assigned if \< 16 years old at randomization. Each score is on a 10-100 point scale and is assigned in 10-point increments (i.e. 10, 20, 30, etc.). A higher score represents a better outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=74 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=88 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Efficacy: Lansky Scores
|
94.73 Scores on a scale
Standard Deviation 10.46
|
94.55 Scores on a scale
Standard Deviation 12.86
|
SECONDARY outcome
Timeframe: BaselinePopulation: Scores were assigned at baseline, 18-months post-randomization, and 30-months post-randomization. Reasons for missing scores include lost to follow-up and clinicians not assigning scores at each visit.
Validated functional performance score, assigned by clinician assessment: Karnofsky score is assigned if \>=16 years at randomization. Each score is on a 10-100 point scale and is assigned in 10-point increments (i.e. 10, 20, 30, etc.). A higher score represents a better outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=12 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=9 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Efficacy: Karnofsky Scores
|
91.67 Scores on a scale
Standard Deviation 8.35
|
92.22 Scores on a scale
Standard Deviation 8.33
|
SECONDARY outcome
Timeframe: 18 months post-randomizationPopulation: Scores were assigned at baseline, 18-months post-randomization, and 30-months post-randomization. Reasons for missing scores include lost to follow-up and clinicians not assigning scores at each visit.
Validated functional performance score, assigned by clinician assessment: Karnofsky score is assigned if \>=16 years at randomization. Each score is on a 10-100 point scale and is assigned in 10-point increments (i.e. 10, 20, 30, etc.). A higher score represents a better outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=12 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=10 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Efficacy: Karnofsky Scores
|
93.75 Scores on a scale
Standard Deviation 7.72
|
95 Scores on a scale
Standard Deviation 7.07
|
SECONDARY outcome
Timeframe: 30 months post-randomizationPopulation: Scores were assigned at baseline, 18-months post-randomization, and 30-months post-randomization. Reasons for missing scores include lost to follow-up and clinicians not assigning scores at each visit.
Validated functional performance score, assigned by clinician assessment: Karnofsky score is assigned if \>=16 years at randomization. Each score is on a 10-100 point scale and is assigned in 10-point increments (i.e. 10, 20, 30, etc.). A higher score represents a better outcome.
Outcome measures
| Measure |
Tacrolimus/Mycophenolate Mofetil
n=11 Participants
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
Everolimus/Low-Dose Tacrolimus
n=10 Participants
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
|---|---|---|
|
Efficacy: Karnofsky Scores
|
94.27 Scores on a scale
Standard Deviation 7.13
|
91 Scores on a scale
Standard Deviation 19.12
|
Adverse Events
Everolimus/Low-Dose Tacrolimus
Serious events: 76 serious events
Other events: 101 other events
Deaths: 3 deaths
Tacrolimus/Mycophenolate Mofetil
Serious events: 60 serious events
Other events: 100 other events
Deaths: 3 deaths
Serious adverse events
| Measure |
Everolimus/Low-Dose Tacrolimus
n=107 participants at risk
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
Tacrolimus/Mycophenolate Mofetil
n=104 participants at risk
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
|---|---|---|
|
Cardiac disorders
Myocarditis
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Cardiac disorders
Palpitations
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
0.00%
0/104 • From consent until end of follow-up, up to 33 months
|
|
Cardiac disorders
Sinus tachycardia
|
1.9%
2/107 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
0.00%
0/104 • From consent until end of follow-up, up to 33 months
|
|
Cardiac disorders
Ventricular tachycardia
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Endocrine disorders
Adrenal insufficiency
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
0.00%
0/104 • From consent until end of follow-up, up to 33 months
|
|
Endocrine disorders
Endocrine disorders - Other, specify
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Eye disorders
Eye disorders - Other, specify
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
0.00%
0/104 • From consent until end of follow-up, up to 33 months
|
|
General disorders
Fever
|
2.8%
3/107 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
1.9%
2/104 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
|
General disorders
Gait disturbance
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
General disorders
General disorders conditions - Other
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
1.9%
2/104 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
|
General disorders
Pain
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
0.00%
0/104 • From consent until end of follow-up, up to 33 months
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Hepatobiliary disorders
Hepatobiliary disorders - Other, specify
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
1.9%
2/104 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
|
Immune system disorders
Autoimmune disorder
|
0.93%
1/107 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
0.00%
0/104 • From consent until end of follow-up, up to 33 months
|
|
Immune system disorders
Immune system disorders - Other, specify
|
12.1%
13/107 • Number of events 23 • From consent until end of follow-up, up to 33 months
|
18.3%
19/104 • Number of events 30 • From consent until end of follow-up, up to 33 months
|
|
Infections and infestations
Anorectal infection
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
0.00%
0/104 • From consent until end of follow-up, up to 33 months
|
|
Infections and infestations
Appendicitis
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
1.9%
2/104 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
|
Infections and infestations
Catheter related infection
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Infections and infestations
Enterocolitis infectious
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
3.8%
4/104 • Number of events 5 • From consent until end of follow-up, up to 33 months
|
|
Infections and infestations
Infections and infestations - Other, specify
|
15.9%
17/107 • Number of events 21 • From consent until end of follow-up, up to 33 months
|
12.5%
13/104 • Number of events 15 • From consent until end of follow-up, up to 33 months
|
|
Infections and infestations
Kidney infection
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Infections and infestations
Lung infection
|
17.8%
19/107 • Number of events 29 • From consent until end of follow-up, up to 33 months
|
15.4%
16/104 • Number of events 27 • From consent until end of follow-up, up to 33 months
|
|
Infections and infestations
Otitis media
|
1.9%
2/107 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
0.00%
0/104 • From consent until end of follow-up, up to 33 months
|
|
Infections and infestations
Sepsis
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Infections and infestations
Sinusitis
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
1.9%
2/104 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
|
Infections and infestations
Skin infection
|
2.8%
3/107 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
2.9%
3/104 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
|
Infections and infestations
Tracheitis
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 4 • From consent until end of follow-up, up to 33 months
|
|
Infections and infestations
Upper respiratory infection
|
8.4%
9/107 • Number of events 12 • From consent until end of follow-up, up to 33 months
|
4.8%
5/104 • Number of events 5 • From consent until end of follow-up, up to 33 months
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Injury, poisoning and procedural complications
Fracture
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications - Other,
|
1.9%
2/107 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
3.8%
4/104 • Number of events 4 • From consent until end of follow-up, up to 33 months
|
|
Injury, poisoning and procedural complications
Vascular access complication
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Investigations
Investigations - Other, specify
|
4.7%
5/107 • Number of events 6 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
|
Investigations
Weight loss
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
0.00%
0/104 • From consent until end of follow-up, up to 33 months
|
|
Metabolism and nutrition disorders
Dehydration
|
11.2%
12/107 • Number of events 15 • From consent until end of follow-up, up to 33 months
|
7.7%
8/104 • Number of events 8 • From consent until end of follow-up, up to 33 months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders - Other, specify
|
1.9%
2/107 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
2.9%
3/104 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
|
Musculoskeletal and connective tissue disorders
Joint effusion
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts
|
1.9%
2/107 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Nervous system disorders
Dizziness
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
0.00%
0/104 • From consent until end of follow-up, up to 33 months
|
|
Nervous system disorders
Headache
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
0.00%
0/104 • From consent until end of follow-up, up to 33 months
|
|
Nervous system disorders
Movements involuntary
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Nervous system disorders
Nervous system disorders - Other, specify
|
1.9%
2/107 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Nervous system disorders
Seizure
|
3.7%
4/107 • Number of events 5 • From consent until end of follow-up, up to 33 months
|
0.00%
0/104 • From consent until end of follow-up, up to 33 months
|
|
Nervous system disorders
Syncope
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
0.00%
0/104 • From consent until end of follow-up, up to 33 months
|
|
Nervous system disorders
Tremor
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
0.00%
0/104 • From consent until end of follow-up, up to 33 months
|
|
Gastrointestinal disorders
Colitis
|
1.9%
2/107 • Number of events 4 • From consent until end of follow-up, up to 33 months
|
0.00%
0/104 • From consent until end of follow-up, up to 33 months
|
|
Gastrointestinal disorders
Constipation
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
0.00%
0/104 • From consent until end of follow-up, up to 33 months
|
|
Gastrointestinal disorders
Diarrhea
|
4.7%
5/107 • Number of events 5 • From consent until end of follow-up, up to 33 months
|
2.9%
3/104 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
|
Gastrointestinal disorders
Enterocolitis
|
0.93%
1/107 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, specify
|
11.2%
12/107 • Number of events 16 • From consent until end of follow-up, up to 33 months
|
7.7%
8/104 • Number of events 11 • From consent until end of follow-up, up to 33 months
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Gastrointestinal disorders
Salivary duct inflammation
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
0.00%
0/104 • From consent until end of follow-up, up to 33 months
|
|
Gastrointestinal disorders
Vomiting
|
1.9%
2/107 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
3.8%
4/104 • Number of events 5 • From consent until end of follow-up, up to 33 months
|
|
Psychiatric disorders
Psychiatric disorders - Other, specify
|
1.9%
2/107 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
0.00%
0/104 • From consent until end of follow-up, up to 33 months
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
2.9%
3/104 • Number of events 4 • From consent until end of follow-up, up to 33 months
|
|
Renal and urinary disorders
Acute kidney injury
|
1.9%
2/107 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Renal and urinary disorders
Renal and urinary disorders - Other, specify
|
1.9%
2/107 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
2.9%
3/104 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
|
Reproductive system and breast disorders
Reproductive system and breast disorders - Other, speci
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
1.9%
2/107 • Number of events 4 • From consent until end of follow-up, up to 33 months
|
1.9%
2/104 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
0.00%
0/104 • From consent until end of follow-up, up to 33 months
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary edema
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other
|
6.5%
7/107 • Number of events 7 • From consent until end of follow-up, up to 33 months
|
5.8%
6/104 • Number of events 8 • From consent until end of follow-up, up to 33 months
|
|
Respiratory, thoracic and mediastinal disorders
Tracheal stenosis
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
0.00%
0/104 • From consent until end of follow-up, up to 33 months
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, specify
|
3.7%
4/107 • Number of events 4 • From consent until end of follow-up, up to 33 months
|
0.00%
0/104 • From consent until end of follow-up, up to 33 months
|
|
Surgical and medical procedures
Surgical and medical procedures - Other, specify
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
1.9%
2/104 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
|
Vascular disorders
Hypertension
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
0.00%
0/104 • From consent until end of follow-up, up to 33 months
|
|
Vascular disorders
Thromboembolic event
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
1.9%
2/104 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
|
Vascular disorders
Vascular disorders - Other, specify
|
1.9%
2/107 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
5.8%
6/104 • Number of events 6 • From consent until end of follow-up, up to 33 months
|
|
Gastrointestinal disorders
Mucositis oral
|
3.7%
4/107 • Number of events 5 • From consent until end of follow-up, up to 33 months
|
0.00%
0/104 • From consent until end of follow-up, up to 33 months
|
|
Blood and lymphatic system disorders
Anemia
|
1.9%
2/107 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
5.8%
6/104 • Number of events 18 • From consent until end of follow-up, up to 33 months
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders - Other, specify
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Cardiac disorders
Atrial flutter
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
|
Cardiac disorders
Cardiac arrest
|
1.9%
2/107 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
1.9%
2/104 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
|
Cardiac disorders
Cardiac disorders - Other, specify
|
2.8%
3/107 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Cardiac disorders
Chest pain - cardiac
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Cardiac disorders
Conduction disorder
|
0.93%
1/107 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
0.00%
0/104 • From consent until end of follow-up, up to 33 months
|
|
Cardiac disorders
Heart failure
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
1.9%
2/104 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
Other adverse events
| Measure |
Everolimus/Low-Dose Tacrolimus
n=107 participants at risk
Everolimus approximately 0.6 mg/m2/dose taken by mouth every 12 hours for 30 months. Everolimus dose will be adjusted to achieve a trough concentration of 3-8 ng/ml.
Tacrolimus 0.0125 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 3-5 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 2.5-4.5 ng/mL.)
|
Tacrolimus/Mycophenolate Mofetil
n=104 participants at risk
Tacrolimus 0.05 mg/kg/dose by mouth every 12 hours for 30 months. (Tacrolimus dose will be adjusted to achieve a trough concentration of 7-10 ng/ml until subjects are 1 year post-heart transplant. After 1 year post-heart transplant the tacrolimus dose will be adjusted to achieve a trough concentration of 5-8 ng/mL.)
Mycophenolate mofetil 600 mg/m2/dose by mouth every 12 hours for 30 months.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
9.3%
10/107 • Number of events 11 • From consent until end of follow-up, up to 33 months
|
12.5%
13/104 • Number of events 15 • From consent until end of follow-up, up to 33 months
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders - Other, specify
|
4.7%
5/107 • Number of events 5 • From consent until end of follow-up, up to 33 months
|
9.6%
10/104 • Number of events 12 • From consent until end of follow-up, up to 33 months
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
2.8%
3/107 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
2.9%
3/104 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
|
Cardiac disorders
Cardiac disorders - Other, specify
|
1.9%
2/107 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
2.9%
3/104 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
|
Endocrine disorders
Endocrine disorders - Other, specify
|
1.9%
2/107 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
2.9%
3/104 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
|
Gastrointestinal Disorders
Constipation
|
2.8%
3/107 • Number of events 4 • From consent until end of follow-up, up to 33 months
|
2.9%
3/104 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
|
Gastrointestinal Disorders
Diarrhea
|
19.6%
21/107 • Number of events 23 • From consent until end of follow-up, up to 33 months
|
18.3%
19/104 • Number of events 27 • From consent until end of follow-up, up to 33 months
|
|
Gastrointestinal Disorders
Gastrointestinal disorders - Other, specify
|
16.8%
18/107 • Number of events 21 • From consent until end of follow-up, up to 33 months
|
26.9%
28/104 • Number of events 35 • From consent until end of follow-up, up to 33 months
|
|
Gastrointestinal Disorders
Mucositis oral
|
30.8%
33/107 • Number of events 38 • From consent until end of follow-up, up to 33 months
|
6.7%
7/104 • Number of events 7 • From consent until end of follow-up, up to 33 months
|
|
Gastrointestinal Disorders
Vomiting
|
9.3%
10/107 • Number of events 13 • From consent until end of follow-up, up to 33 months
|
11.5%
12/104 • Number of events 12 • From consent until end of follow-up, up to 33 months
|
|
General disorders
Fever
|
9.3%
10/107 • Number of events 12 • From consent until end of follow-up, up to 33 months
|
8.7%
9/104 • Number of events 13 • From consent until end of follow-up, up to 33 months
|
|
General disorders
Flu like symptoms
|
3.7%
4/107 • Number of events 4 • From consent until end of follow-up, up to 33 months
|
2.9%
3/104 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
|
General disorders
General disorders and administration site conditions -
|
2.8%
3/107 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
2.9%
3/104 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
|
General disorders
Infusion related reaction
|
2.8%
3/107 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
General disorders
Non-cardiac chest pain
|
7.5%
8/107 • Number of events 8 • From consent until end of follow-up, up to 33 months
|
1.9%
2/104 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
|
Immune system disorders
Allergic reaction
|
5.6%
6/107 • Number of events 8 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Immune system disorders
Immune system disorders - Other, specify
|
15.0%
16/107 • Number of events 21 • From consent until end of follow-up, up to 33 months
|
20.2%
21/104 • Number of events 31 • From consent until end of follow-up, up to 33 months
|
|
Infections and infestations
Enterocolitis infectious
|
2.8%
3/107 • Number of events 4 • From consent until end of follow-up, up to 33 months
|
4.8%
5/104 • Number of events 7 • From consent until end of follow-up, up to 33 months
|
|
Infections and infestations
Infections and infestations - Other, specify
|
40.2%
43/107 • Number of events 73 • From consent until end of follow-up, up to 33 months
|
34.6%
36/104 • Number of events 63 • From consent until end of follow-up, up to 33 months
|
|
Infections and infestations
Lip infection
|
1.9%
2/107 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
2.9%
3/104 • Number of events 4 • From consent until end of follow-up, up to 33 months
|
|
Infections and infestations
Lung infection
|
9.3%
10/107 • Number of events 11 • From consent until end of follow-up, up to 33 months
|
12.5%
13/104 • Number of events 13 • From consent until end of follow-up, up to 33 months
|
|
Infections and infestations
Otitis media
|
22.4%
24/107 • Number of events 38 • From consent until end of follow-up, up to 33 months
|
17.3%
18/104 • Number of events 22 • From consent until end of follow-up, up to 33 months
|
|
Infections and infestations
Pharyngitis
|
2.8%
3/107 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
2.9%
3/104 • Number of events 4 • From consent until end of follow-up, up to 33 months
|
|
Infections and infestations
Sinusitis
|
4.7%
5/107 • Number of events 5 • From consent until end of follow-up, up to 33 months
|
4.8%
5/104 • Number of events 9 • From consent until end of follow-up, up to 33 months
|
|
Infections and infestations
Skin infection
|
9.3%
10/107 • Number of events 13 • From consent until end of follow-up, up to 33 months
|
5.8%
6/104 • Number of events 6 • From consent until end of follow-up, up to 33 months
|
|
Infections and infestations
Upper respiratory infection
|
29.0%
31/107 • Number of events 59 • From consent until end of follow-up, up to 33 months
|
27.9%
29/104 • Number of events 42 • From consent until end of follow-up, up to 33 months
|
|
Infections and infestations
Urinary tract infection
|
8.4%
9/107 • Number of events 11 • From consent until end of follow-up, up to 33 months
|
4.8%
5/104 • Number of events 6 • From consent until end of follow-up, up to 33 months
|
|
Injury, poisoning and procedural complications
Fracture
|
4.7%
5/107 • Number of events 5 • From consent until end of follow-up, up to 33 months
|
5.8%
6/104 • Number of events 6 • From consent until end of follow-up, up to 33 months
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications - Other,
|
4.7%
5/107 • Number of events 5 • From consent until end of follow-up, up to 33 months
|
4.8%
5/104 • Number of events 5 • From consent until end of follow-up, up to 33 months
|
|
Investigations
Alanine aminotransferase increased
|
3.7%
4/107 • Number of events 4 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Investigations
Aspartate aminotransferase increased
|
3.7%
4/107 • Number of events 4 • From consent until end of follow-up, up to 33 months
|
1.9%
2/104 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
|
Investigations
Investigations - Other, specify
|
17.8%
19/107 • Number of events 20 • From consent until end of follow-up, up to 33 months
|
6.7%
7/104 • Number of events 10 • From consent until end of follow-up, up to 33 months
|
|
Investigations
Lymphocyte count decreased
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
2.9%
3/104 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
|
Investigations
Neutrophil count decreased
|
7.5%
8/107 • Number of events 9 • From consent until end of follow-up, up to 33 months
|
9.6%
10/104 • Number of events 12 • From consent until end of follow-up, up to 33 months
|
|
Investigations
Weight loss
|
2.8%
3/107 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
3.8%
4/104 • Number of events 4 • From consent until end of follow-up, up to 33 months
|
|
Investigations
White blood cell decreased
|
1.9%
2/107 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
6.7%
7/104 • Number of events 9 • From consent until end of follow-up, up to 33 months
|
|
Metabolism and nutrition disorders
Acidosis
|
6.5%
7/107 • Number of events 7 • From consent until end of follow-up, up to 33 months
|
5.8%
6/104 • Number of events 6 • From consent until end of follow-up, up to 33 months
|
|
Metabolism and nutrition disorders
Dehydration
|
6.5%
7/107 • Number of events 9 • From consent until end of follow-up, up to 33 months
|
10.6%
11/104 • Number of events 12 • From consent until end of follow-up, up to 33 months
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
4.8%
5/104 • Number of events 5 • From consent until end of follow-up, up to 33 months
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
2.8%
3/107 • Number of events 4 • From consent until end of follow-up, up to 33 months
|
1.9%
2/104 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
3.8%
4/104 • Number of events 4 • From consent until end of follow-up, up to 33 months
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
1.9%
2/107 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
4.8%
5/104 • Number of events 5 • From consent until end of follow-up, up to 33 months
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders - Other, specify
|
1.9%
2/107 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
11.5%
12/104 • Number of events 12 • From consent until end of follow-up, up to 33 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
2.9%
3/104 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.8%
3/107 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
0.00%
0/104 • From consent until end of follow-up, up to 33 months
|
|
Nervous system disorders
Dizziness
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
2.9%
3/104 • Number of events 4 • From consent until end of follow-up, up to 33 months
|
|
Nervous system disorders
Headache
|
5.6%
6/107 • Number of events 7 • From consent until end of follow-up, up to 33 months
|
7.7%
8/104 • Number of events 9 • From consent until end of follow-up, up to 33 months
|
|
Nervous system disorders
Nervous system disorders - Other, specify
|
3.7%
4/107 • Number of events 6 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Nervous system disorders
Seizure
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
2.9%
3/104 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
|
Psychiatric disorders
Anxiety
|
1.9%
2/107 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
3.8%
4/104 • Number of events 4 • From consent until end of follow-up, up to 33 months
|
|
Psychiatric disorders
Depression
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
2.9%
3/104 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
|
Renal and urinary disorders
Acute kidney injury
|
6.5%
7/107 • Number of events 7 • From consent until end of follow-up, up to 33 months
|
10.6%
11/104 • Number of events 12 • From consent until end of follow-up, up to 33 months
|
|
Renal and urinary disorders
Proteinuria
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
2.9%
3/104 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
|
Reproductive system and breast disorders
Menorrhagia
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
2.9%
3/104 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
2.8%
3/107 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
1.9%
2/104 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
11.2%
12/107 • Number of events 12 • From consent until end of follow-up, up to 33 months
|
13.5%
14/104 • Number of events 15 • From consent until end of follow-up, up to 33 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
1.9%
2/107 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
3.8%
4/104 • Number of events 5 • From consent until end of follow-up, up to 33 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
3.8%
4/104 • Number of events 4 • From consent until end of follow-up, up to 33 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other
|
9.3%
10/107 • Number of events 10 • From consent until end of follow-up, up to 33 months
|
11.5%
12/104 • Number of events 17 • From consent until end of follow-up, up to 33 months
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
2.9%
3/104 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
2.8%
3/107 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
0.96%
1/104 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
4.7%
5/107 • Number of events 5 • From consent until end of follow-up, up to 33 months
|
2.9%
3/104 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, specify
|
21.5%
23/107 • Number of events 28 • From consent until end of follow-up, up to 33 months
|
23.1%
24/104 • Number of events 29 • From consent until end of follow-up, up to 33 months
|
|
Surgical and medical procedures
Surgical and medical procedures - Other, specify
|
5.6%
6/107 • Number of events 7 • From consent until end of follow-up, up to 33 months
|
6.7%
7/104 • Number of events 7 • From consent until end of follow-up, up to 33 months
|
|
Vascular disorders
Hypertension
|
3.7%
4/107 • Number of events 4 • From consent until end of follow-up, up to 33 months
|
1.9%
2/104 • Number of events 2 • From consent until end of follow-up, up to 33 months
|
|
Vascular disorders
Hypotension
|
0.00%
0/107 • From consent until end of follow-up, up to 33 months
|
2.9%
3/104 • Number of events 3 • From consent until end of follow-up, up to 33 months
|
|
Vascular disorders
Vascular disorders - Other, specify
|
0.93%
1/107 • Number of events 1 • From consent until end of follow-up, up to 33 months
|
6.7%
7/104 • Number of events 8 • From consent until end of follow-up, up to 33 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place