Trial Outcomes & Findings for Randomized Conversion of Calcineurin-Inhibitors in Renal Allograft Recipients (NCT NCT00866879)
NCT ID: NCT00866879
Last Updated: 2019-06-28
Results Overview
The primary purpose of this research study is to evaluate whether the use of mycophenolate mofetil/Cellcept ® and either tacrolimus/Prograf ® (Group #1) or mycophenolate mofetil/Cellcept ® and sirolimus/Rapamune® (Group #2) impacts the incidence of acute cellular rejection in post-kidney transplant patients. This study will examine whether switching from tacrolimus to sirolimus will better preserve long-term kidney function.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
275 participants
Primary outcome timeframe
Assessed at 6 Months, 12 Months, 24 Months, months 24 reported
Results posted on
2019-06-28
Participant Flow
Donor participants were no part of our outcome analysis because their participation was only on the basis of providing blood for testing the immune system of the recipients. The analysis of the recipients was intention to treat therefore all recipient participants completed the study period
Participant milestones
| Measure |
Control
Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus.
|
Transition to Sirolimus Group
Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus
|
|---|---|---|
|
Overall Study
STARTED
|
90
|
185
|
|
Overall Study
COMPLETED
|
90
|
185
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Randomized Conversion of Calcineurin-Inhibitors in Renal Allograft Recipients
Baseline characteristics by cohort
| Measure |
Control
n=90 Participants
Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus.
|
Transition to Sirolimus Group
n=185 Participants
Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus
|
Total
n=275 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
Age in years
|
39.2 years
STANDARD_DEVIATION 12.6 • n=99 Participants
|
38.8 years
STANDARD_DEVIATION 12.5 • n=107 Participants
|
38.9 years
STANDARD_DEVIATION 12.6 • n=206 Participants
|
|
Sex/Gender, Customized
Sex male
|
55 Participants
n=99 Participants
|
106 Participants
n=107 Participants
|
161 Participants
n=206 Participants
|
|
Sex/Gender, Customized
Sex female
|
35 Participants
n=99 Participants
|
79 Participants
n=107 Participants
|
114 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
white
|
44 Participants
n=99 Participants
|
83 Participants
n=107 Participants
|
127 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
AA
|
24 Participants
n=99 Participants
|
37 Participants
n=107 Participants
|
61 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
17 Participants
n=99 Participants
|
45 Participants
n=107 Participants
|
62 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
other
|
5 Participants
n=99 Participants
|
20 Participants
n=107 Participants
|
25 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
90 participants
n=99 Participants
|
185 participants
n=107 Participants
|
275 participants
n=206 Participants
|
|
HLA mismatch
|
3.9 HLA antigens
STANDARD_DEVIATION 1.7 • n=99 Participants
|
3.61 HLA antigens
STANDARD_DEVIATION 1.82 • n=107 Participants
|
3.8 HLA antigens
STANDARD_DEVIATION 1.8 • n=206 Participants
|
|
Donor type
Living donors
|
63 Participants
n=99 Participants
|
130 Participants
n=107 Participants
|
193 Participants
n=206 Participants
|
|
Donor type
Cadaveric kidneys
|
27 Participants
n=99 Participants
|
55 Participants
n=107 Participants
|
82 Participants
n=206 Participants
|
|
PRA >20%
|
14 Participants
n=99 Participants
|
24 Participants
n=107 Participants
|
38 Participants
n=206 Participants
|
|
Diabetis mellitus
|
26 Participants
n=99 Participants
|
69 Participants
n=107 Participants
|
95 Participants
n=206 Participants
|
|
Elevated blood pressure
|
76 Participants
n=99 Participants
|
158 Participants
n=107 Participants
|
234 Participants
n=206 Participants
|
|
Coronary artery disease (CAD)
|
10 Participants
n=99 Participants
|
31 Participants
n=107 Participants
|
41 Participants
n=206 Participants
|
|
Smoking
|
9 Participants
n=99 Participants
|
29 Participants
n=107 Participants
|
38 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Assessed at 6 Months, 12 Months, 24 Months, months 24 reportedThe primary purpose of this research study is to evaluate whether the use of mycophenolate mofetil/Cellcept ® and either tacrolimus/Prograf ® (Group #1) or mycophenolate mofetil/Cellcept ® and sirolimus/Rapamune® (Group #2) impacts the incidence of acute cellular rejection in post-kidney transplant patients. This study will examine whether switching from tacrolimus to sirolimus will better preserve long-term kidney function.
Outcome measures
| Measure |
Control
n=90 Participants
Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus.
|
Transition to Sirolimus Group
n=185 Participants
Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus
|
|---|---|---|
|
Incidence of Acute Cellular Rejection
|
7 Participants
|
31 Participants
|
SECONDARY outcome
Timeframe: Assessed at 6 Months, 12 Months, 24 Months, months 24 reportedEvaluate whether CI conversion (tacrolimus→sirolimus) contributes positively or negatively on the renal allograft function calculated with e-GFR and proteinuria
Outcome measures
| Measure |
Control
n=90 Participants
Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus.
|
Transition to Sirolimus Group
n=185 Participants
Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus
|
|---|---|---|
|
Renal Allograft Function Calculated With e-GFR and Proteinuria
|
57.6 mL/min
Standard Deviation 20.4
|
58.4 mL/min
Standard Deviation 25.2
|
SECONDARY outcome
Timeframe: Assessed at 6 Months, 12 Months, 24 Months, months 24 reportedIn addition to monitoring renal allograft function, evaluation will be conducted on the incidence of acute rejection, patient and graft survival, the impact of CI conversion on the lipid profile, the incidence of hypertension, malignancies, opportunistic infections and post-transplant DM (de novo diabetes mellitus).
Outcome measures
| Measure |
Control
n=90 Participants
Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus.
|
Transition to Sirolimus Group
n=185 Participants
Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus
|
|---|---|---|
|
Evaluate if CI Conversion Impacts on Lipid Profile, Incidence of Hypertension, Malignancies, and Opportunistic Infections and Post-transplant DM
Infections
|
33 number of incidents
|
83 number of incidents
|
|
Evaluate if CI Conversion Impacts on Lipid Profile, Incidence of Hypertension, Malignancies, and Opportunistic Infections and Post-transplant DM
Malignancies
|
4 number of incidents
|
9 number of incidents
|
|
Evaluate if CI Conversion Impacts on Lipid Profile, Incidence of Hypertension, Malignancies, and Opportunistic Infections and Post-transplant DM
Proteinura
|
12 number of incidents
|
61 number of incidents
|
|
Evaluate if CI Conversion Impacts on Lipid Profile, Incidence of Hypertension, Malignancies, and Opportunistic Infections and Post-transplant DM
Hyperlipidemia
|
9 number of incidents
|
19 number of incidents
|
|
Evaluate if CI Conversion Impacts on Lipid Profile, Incidence of Hypertension, Malignancies, and Opportunistic Infections and Post-transplant DM
NODAT
|
3 number of incidents
|
2 number of incidents
|
|
Evaluate if CI Conversion Impacts on Lipid Profile, Incidence of Hypertension, Malignancies, and Opportunistic Infections and Post-transplant DM
BK viremia
|
15 number of incidents
|
28 number of incidents
|
|
Evaluate if CI Conversion Impacts on Lipid Profile, Incidence of Hypertension, Malignancies, and Opportunistic Infections and Post-transplant DM
BK nephropathy
|
1 number of incidents
|
5 number of incidents
|
|
Evaluate if CI Conversion Impacts on Lipid Profile, Incidence of Hypertension, Malignancies, and Opportunistic Infections and Post-transplant DM
Neutropenia
|
22 number of incidents
|
35 number of incidents
|
SECONDARY outcome
Timeframe: Assessed at 6 Months, 12 Months, 24 Months, months 24 reportedThis study also reviews the impact of the immunosuppressive medications on patient and graft survival.
Outcome measures
| Measure |
Control
n=90 Participants
Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus.
|
Transition to Sirolimus Group
n=185 Participants
Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus
|
|---|---|---|
|
Patient and Graft Survival
Kidney transplant loss
|
4 number of incidents
|
12 number of incidents
|
|
Patient and Graft Survival
Patient death
|
3 number of incidents
|
10 number of incidents
|
SECONDARY outcome
Timeframe: Assessed at 6 Months, 12 Months, 24 Months, months 24 reportedSpecifically we reported here the percentage of regulatory T cells that were present in the two groups at 24 months post randomization. With peripheral leukocytes taken at baseline (first visit) prior to randomization and at 6, 12 and 24 Months post-randomization, researchers will also review possible modifications of lymphocytes function and of the lymphocytes subpopulations that might have occurred as a consequence of the switch from tacrolimus to sirolimus (randomization).
Outcome measures
| Measure |
Control
n=90 Participants
Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus.
|
Transition to Sirolimus Group
n=185 Participants
Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus
|
|---|---|---|
|
Percentage of Regulatory T Cells
|
75 % of Treg Cells
Standard Deviation 7.1
|
98 % of Treg Cells
Standard Deviation 10.8
|
Adverse Events
Control
Serious events: 42 serious events
Other events: 58 other events
Deaths: 3 deaths
Transition to Sirolimus
Serious events: 117 serious events
Other events: 135 other events
Deaths: 10 deaths
Serious adverse events
| Measure |
Control
n=90 participants at risk
Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus. Patients were followed for 24 months post randomization
|
Transition to Sirolimus
n=185 participants at risk
Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus. Patients were followed for 24 months post randomization
|
|---|---|---|
|
Renal and urinary disorders
Renal allograft loss
|
4.4%
4/90 • Number of events 4 • 24 months
Donor participants were no part of our outcome analysis because their participation was only on the basis of providing blood for testing the immune system of the recipients. The analysis of the recipients was intention to treat therefore all recipient participants completed the study period
|
6.5%
12/185 • Number of events 12 • 24 months
Donor participants were no part of our outcome analysis because their participation was only on the basis of providing blood for testing the immune system of the recipients. The analysis of the recipients was intention to treat therefore all recipient participants completed the study period
|
|
Renal and urinary disorders
Proteinuria
|
13.3%
12/90 • Number of events 12 • 24 months
Donor participants were no part of our outcome analysis because their participation was only on the basis of providing blood for testing the immune system of the recipients. The analysis of the recipients was intention to treat therefore all recipient participants completed the study period
|
33.0%
61/185 • Number of events 61 • 24 months
Donor participants were no part of our outcome analysis because their participation was only on the basis of providing blood for testing the immune system of the recipients. The analysis of the recipients was intention to treat therefore all recipient participants completed the study period
|
|
Blood and lymphatic system disorders
Neutropenia
|
24.4%
22/90 • Number of events 22 • 24 months
Donor participants were no part of our outcome analysis because their participation was only on the basis of providing blood for testing the immune system of the recipients. The analysis of the recipients was intention to treat therefore all recipient participants completed the study period
|
18.9%
35/185 • Number of events 35 • 24 months
Donor participants were no part of our outcome analysis because their participation was only on the basis of providing blood for testing the immune system of the recipients. The analysis of the recipients was intention to treat therefore all recipient participants completed the study period
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignancies
|
4.4%
4/90 • Number of events 4 • 24 months
Donor participants were no part of our outcome analysis because their participation was only on the basis of providing blood for testing the immune system of the recipients. The analysis of the recipients was intention to treat therefore all recipient participants completed the study period
|
4.9%
9/185 • Number of events 9 • 24 months
Donor participants were no part of our outcome analysis because their participation was only on the basis of providing blood for testing the immune system of the recipients. The analysis of the recipients was intention to treat therefore all recipient participants completed the study period
|
Other adverse events
| Measure |
Control
n=90 participants at risk
Group 1 will continue immunosuppression medication per standard of care (SOC) at Northwestern by taking mycophenolate mofetil and tacrolimus. Patients were followed for 24 months post randomization
|
Transition to Sirolimus
n=185 participants at risk
Group 2 will switch immunosuppression medication to taking mycophenolate mofetil and sirolimus. Patients were followed for 24 months post randomization
|
|---|---|---|
|
Infections and infestations
Infections
|
36.7%
33/90 • Number of events 33 • 24 months
Donor participants were no part of our outcome analysis because their participation was only on the basis of providing blood for testing the immune system of the recipients. The analysis of the recipients was intention to treat therefore all recipient participants completed the study period
|
44.9%
83/185 • Number of events 83 • 24 months
Donor participants were no part of our outcome analysis because their participation was only on the basis of providing blood for testing the immune system of the recipients. The analysis of the recipients was intention to treat therefore all recipient participants completed the study period
|
|
Cardiac disorders
Hyperlipidemia
|
10.0%
9/90 • Number of events 9 • 24 months
Donor participants were no part of our outcome analysis because their participation was only on the basis of providing blood for testing the immune system of the recipients. The analysis of the recipients was intention to treat therefore all recipient participants completed the study period
|
10.3%
19/185 • Number of events 19 • 24 months
Donor participants were no part of our outcome analysis because their participation was only on the basis of providing blood for testing the immune system of the recipients. The analysis of the recipients was intention to treat therefore all recipient participants completed the study period
|
|
Endocrine disorders
Diabetes
|
3.3%
3/90 • Number of events 3 • 24 months
Donor participants were no part of our outcome analysis because their participation was only on the basis of providing blood for testing the immune system of the recipients. The analysis of the recipients was intention to treat therefore all recipient participants completed the study period
|
1.1%
2/185 • Number of events 3 • 24 months
Donor participants were no part of our outcome analysis because their participation was only on the basis of providing blood for testing the immune system of the recipients. The analysis of the recipients was intention to treat therefore all recipient participants completed the study period
|
|
Renal and urinary disorders
BK viremia
|
16.7%
15/90 • Number of events 15 • 24 months
Donor participants were no part of our outcome analysis because their participation was only on the basis of providing blood for testing the immune system of the recipients. The analysis of the recipients was intention to treat therefore all recipient participants completed the study period
|
15.1%
28/185 • Number of events 28 • 24 months
Donor participants were no part of our outcome analysis because their participation was only on the basis of providing blood for testing the immune system of the recipients. The analysis of the recipients was intention to treat therefore all recipient participants completed the study period
|
|
Renal and urinary disorders
BK nephropathy
|
1.1%
1/90 • Number of events 1 • 24 months
Donor participants were no part of our outcome analysis because their participation was only on the basis of providing blood for testing the immune system of the recipients. The analysis of the recipients was intention to treat therefore all recipient participants completed the study period
|
2.7%
5/185 • Number of events 5 • 24 months
Donor participants were no part of our outcome analysis because their participation was only on the basis of providing blood for testing the immune system of the recipients. The analysis of the recipients was intention to treat therefore all recipient participants completed the study period
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place