Trial Outcomes & Findings for Study to Evaluate the Efficacy, Safety and Tolerability of Everolimus in de Novo Renal Transplant Recipients Participating in the Eurotransplant Senior Program (NCT NCT00956293)
NCT ID: NCT00956293
Last Updated: 2014-06-06
Results Overview
The study was terminated prematurely and not powered for efficacy.
TERMINATED
PHASE4
207 participants
Month 6
2014-06-06
Participant Flow
The study consisted of a main period and a 54 month observation follow-up period. The main period included a pre-randomized treatment phase (6 weeks) and a randomized treatment phase (18 weeks). All randomized participants, who participated in the main period, were eligible for the follow-up period.
At baseline (BL) 1 (pre-randomization), eligible participants received a CNI-based regimen for 6 weeks. At BL2 (randomization), eligible participants were randomized in a 1:2 ratio to the control group or everolimus group.
Participant milestones
| Measure |
Control Group
During the pre-randomized treatment phase, all participants received a CNI-based regimen consisting of basiliximab, mycophenolic acid (MPA), cyclosporin A (CsA) and corticosteroids (optional). Upon randomization, participants in this group continued with a CNI-based regimen of MPA and CsA.
|
Everolimus Group
During the pre-randomized treatment phase, all participants received a CNI-based regimen consisting of basiliximab, mycophenolic acid (MPA), cyclosporin A (CsA) and corticosteroids (optional). Upon randomization, participants in this group made a stepwise switch to a CNI-free regimen of everolimus and MPA.
|
Pre-randomized Group
Participants, who met BL1 eligibility, were enrolled into the study.
|
|---|---|---|---|
|
Main Period (Pre-randomization)
STARTED
|
0
|
0
|
207
|
|
Main Period (Pre-randomization)
Enrolled Safety Set
|
0
|
0
|
203
|
|
Main Period (Pre-randomization)
COMPLETED
|
0
|
0
|
77
|
|
Main Period (Pre-randomization)
NOT COMPLETED
|
0
|
0
|
130
|
|
Main Period (Randomization)
STARTED
|
24
|
53
|
0
|
|
Main Period (Randomization)
Full Analysis Set
|
24
|
51
|
0
|
|
Main Period (Randomization)
Randomized Safety Set
|
24
|
51
|
0
|
|
Main Period (Randomization)
COMPLETED
|
23
|
26
|
0
|
|
Main Period (Randomization)
NOT COMPLETED
|
1
|
27
|
0
|
|
Follow-up Period
STARTED
|
20
|
32
|
0
|
|
Follow-up Period
COMPLETED
|
0
|
0
|
0
|
|
Follow-up Period
NOT COMPLETED
|
20
|
32
|
0
|
Reasons for withdrawal
| Measure |
Control Group
During the pre-randomized treatment phase, all participants received a CNI-based regimen consisting of basiliximab, mycophenolic acid (MPA), cyclosporin A (CsA) and corticosteroids (optional). Upon randomization, participants in this group continued with a CNI-based regimen of MPA and CsA.
|
Everolimus Group
During the pre-randomized treatment phase, all participants received a CNI-based regimen consisting of basiliximab, mycophenolic acid (MPA), cyclosporin A (CsA) and corticosteroids (optional). Upon randomization, participants in this group made a stepwise switch to a CNI-free regimen of everolimus and MPA.
|
Pre-randomized Group
Participants, who met BL1 eligibility, were enrolled into the study.
|
|---|---|---|---|
|
Main Period (Pre-randomization)
Not specified (data missing)
|
0
|
0
|
1
|
|
Main Period (Pre-randomization)
Death
|
0
|
0
|
1
|
|
Main Period (Pre-randomization)
Protocol Violation
|
0
|
0
|
1
|
|
Main Period (Pre-randomization)
Abnormal test procedure result
|
0
|
0
|
2
|
|
Main Period (Pre-randomization)
Administrative problems
|
0
|
0
|
6
|
|
Main Period (Pre-randomization)
Graft loss
|
0
|
0
|
7
|
|
Main Period (Pre-randomization)
Withdrawal by Subject
|
0
|
0
|
12
|
|
Main Period (Pre-randomization)
Lack of Efficacy
|
0
|
0
|
20
|
|
Main Period (Pre-randomization)
Adverse Event
|
0
|
0
|
36
|
|
Main Period (Pre-randomization)
Abnormal laboratory value
|
0
|
0
|
44
|
|
Main Period (Randomization)
Abnormal laboratory value
|
0
|
2
|
0
|
|
Main Period (Randomization)
Lack of Efficacy
|
1
|
10
|
0
|
|
Main Period (Randomization)
Adverse Event
|
0
|
15
|
0
|
|
Follow-up Period
Follow-up period was terminated.
|
20
|
32
|
0
|
Baseline Characteristics
Study to Evaluate the Efficacy, Safety and Tolerability of Everolimus in de Novo Renal Transplant Recipients Participating in the Eurotransplant Senior Program
Baseline characteristics by cohort
| Measure |
Control Group
n=24 Participants
During the pre-randomized treatment phase, all participants received a CNI-based regimen consisting of basiliximab, mycophenolic acid (MPA), cyclosporin A (CsA) and corticosteroids (optional). Upon randomization, participants in this group continued with a CNI-based regimen of MPA and CsA.
|
Everolimus Group
n=51 Participants
During the pre-randomized treatment phase, all participants received a CNI-based regimen consisting of basiliximab, mycophenolic acid (MPA), cyclosporin A (CsA) and corticosteroids (optional). Upon randomization, participants in this group made a stepwise switch to a CNI-free regimen of everolimus and MPA.
|
Total
n=75 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
69.3 Years
STANDARD_DEVIATION 3.1 • n=99 Participants
|
68.4 Years
STANDARD_DEVIATION 3.3 • n=107 Participants
|
68.7 Years
STANDARD_DEVIATION 3.3 • n=206 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=99 Participants
|
26 Participants
n=107 Participants
|
34 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=99 Participants
|
25 Participants
n=107 Participants
|
41 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Month 6Population: This outcome measure was not analyzed because a total of 244 completed subjects were needed to have a power of 80% in detecting a significant difference between treatment groups. Due to early termination, the study was limited by a small sample size; hence, the planned analysis was not done.
The study was terminated prematurely and not powered for efficacy.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Month 6Population: This outcome measure was not analyzed because a total of 244 completed subjects were needed to have a power of 80% in detecting a significant difference between treatment groups. Due to early termination, the study was limited by a small sample size; hence, the planned analysis was not done.
The study was terminated prematurely and not powered for efficacy.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Months 6, 12, 24, 36, 48 and 60Population: This outcome measure was not analyzed because a total of 244 completed subjects were needed to have a power of 80% in detecting a significant difference between treatment groups. Due to early termination, the study was limited by a small sample size; hence, the planned analysis was not done.
The study was terminated prematurely and not powered for efficacy.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Months 6, 12, 24, 36, 48 and 60Population: This outcome measure was not analyzed because a total of 244 completed subjects were needed to have a power of 80% in detecting a significant difference between treatment groups. Due to early termination, the study was limited by a small sample size; hence, the planned analysis was not done.
The study was terminated prematurely and not powered for efficacy.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Month 6Population: This outcome measure was not analyzed because a total of 244 completed subjects were needed to have a power of 80% in detecting a significant difference between treatment groups. Due to early termination, the study was limited by a small sample size; hence, the planned analysis was not done.
The study was terminated prematurely and not powered for efficacy.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Week 7, Month 6Population: This outcome measure was not analyzed because a total of 244 completed subjects were needed to have a power of 80% in detecting a significant difference between treatment groups. Due to early termination, the study was limited by a small sample size; hence, the planned analysis was not done.
The study was terminated prematurely and not powered for efficacy.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Month 6Population: This outcome measure was not analyzed because a total of 244 completed subjects were needed to have a power of 80% in detecting a significant difference between treatment groups. Due to early termination, the study was limited by a small sample size; hence, the planned analysis was not done.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Months 6, 12, 24, 36, 48 and 60Population: Randomized Safety Set: This set included all randomized participants who received at least one dose of study medication.
Participants with adverse events (serious plus non-serious), serious adverse events and death were reported.
Outcome measures
| Measure |
Control Group
n=24 Participants
During the pre-randomized treatment phase, all participants received a CNI-based regimen consisting of basiliximab, mycophenolic acid (MPA), cyclosporin A (CsA) and corticosteroids (optional). Upon randomization, participants in this group continued with a CNI-based regimen of MPA and CsA.
|
Everolimus Group
n=51 Participants
During the pre-randomized treatment phase, all participants received a CNI-based regimen consisting of basiliximab, mycophenolic acid (MPA), cyclosporin A (CsA) and corticosteroids (optional). Upon randomization, participants in this group made a stepwise switch to a CNI-free regimen of everolimus and MPA.
|
|---|---|---|
|
Number of Participants Who Experienced Adverse Events, Serious Adverse Events and Death
Adverse events (serious and non-serious)
|
21 Participants
|
50 Participants
|
|
Number of Participants Who Experienced Adverse Events, Serious Adverse Events and Death
Serious adverse events
|
11 Participants
|
28 Participants
|
|
Number of Participants Who Experienced Adverse Events, Serious Adverse Events and Death
Deaths
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Months 12, 24, 36, 48 and 60Population: This outcome measure was not analyzed because a total of 244 completed subjects were needed to have a power of 80% in detecting a significant difference between treatment groups. Due to early termination, the study was limited by a small sample size; hence, the planned analysis was not done.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Months12, 24, 36, 48 and 60Population: This outcome measure was not analyzed because a total of 244 completed subjects were needed to have a power of 80% in detecting a significant difference between treatment groups. Due to early termination, the study was limited by a small sample size; hence, the planned analysis was not done.
Outcome measures
Outcome data not reported
Adverse Events
Control Goup
Everolimus Group
Serious adverse events
| Measure |
Control Goup
n=24 participants at risk
During the pre-randomized treatment phase, all participants received a CNI-based regimen consisting of basiliximab, mycophenolic acid (MPA), cyclosporin A (CsA) and corticosteroids (optional). Upon randomization, participants in this group continued with a CNI-based regimen of MPA and CsA.
|
Everolimus Group
n=51 participants at risk
During the pre-randomized treatment phase, all participants received a CNI-based regimen consisting of basiliximab, mycophenolic acid (MPA), cyclosporin A (CsA) and corticosteroids (optional). Upon randomization, participants in this group made a stepwise switch to a CNI-free regimen of everolimus and MPA.
|
|---|---|---|
|
Blood and lymphatic system disorders
ANAEMIA
|
4.2%
1/24
|
3.9%
2/51
|
|
Blood and lymphatic system disorders
LEUKOPENIA
|
0.00%
0/24
|
5.9%
3/51
|
|
Blood and lymphatic system disorders
PANCYTOPENIA
|
0.00%
0/24
|
3.9%
2/51
|
|
Cardiac disorders
MITRAL VALVE INCOMPETENCE
|
4.2%
1/24
|
0.00%
0/51
|
|
Gastrointestinal disorders
ABDOMINAL MASS
|
0.00%
0/24
|
2.0%
1/51
|
|
Gastrointestinal disorders
APHTHOUS STOMATITIS
|
0.00%
0/24
|
2.0%
1/51
|
|
Gastrointestinal disorders
CROHN'S DISEASE
|
0.00%
0/24
|
2.0%
1/51
|
|
Gastrointestinal disorders
DIARRHOEA
|
0.00%
0/24
|
3.9%
2/51
|
|
Gastrointestinal disorders
ENTEROCOLITIS HAEMORRHAGIC
|
0.00%
0/24
|
2.0%
1/51
|
|
Gastrointestinal disorders
ILEUS PARALYTIC
|
0.00%
0/24
|
2.0%
1/51
|
|
Gastrointestinal disorders
INGUINAL HERNIA
|
0.00%
0/24
|
2.0%
1/51
|
|
General disorders
GENERAL PHYSICAL HEALTH DETERIORATION
|
0.00%
0/24
|
2.0%
1/51
|
|
General disorders
PYREXIA
|
0.00%
0/24
|
2.0%
1/51
|
|
Immune system disorders
TRANSPLANT REJECTION
|
4.2%
1/24
|
0.00%
0/51
|
|
Infections and infestations
BK VIRUS INFECTION
|
0.00%
0/24
|
2.0%
1/51
|
|
Infections and infestations
BRONCHOPULMONARY ASPERGILLOSIS
|
0.00%
0/24
|
2.0%
1/51
|
|
Infections and infestations
CYTOMEGALOVIRUS COLITIS
|
0.00%
0/24
|
2.0%
1/51
|
|
Infections and infestations
FEBRILE INFECTION
|
0.00%
0/24
|
2.0%
1/51
|
|
Infections and infestations
GASTROENTERITIS VIRAL
|
0.00%
0/24
|
2.0%
1/51
|
|
Infections and infestations
GENITAL HERPES
|
0.00%
0/24
|
2.0%
1/51
|
|
Infections and infestations
HEPATIC CYST INFECTION
|
4.2%
1/24
|
0.00%
0/51
|
|
Infections and infestations
HERPES ZOSTER OTICUS
|
0.00%
0/24
|
2.0%
1/51
|
|
Infections and infestations
INFECTION
|
8.3%
2/24
|
2.0%
1/51
|
|
Infections and infestations
PNEUMONIA
|
8.3%
2/24
|
7.8%
4/51
|
|
Infections and infestations
PYELONEPHRITIS ACUTE
|
0.00%
0/24
|
2.0%
1/51
|
|
Infections and infestations
URINARY TRACT INFECTION
|
12.5%
3/24
|
9.8%
5/51
|
|
Infections and infestations
UROSEPSIS
|
0.00%
0/24
|
2.0%
1/51
|
|
Injury, poisoning and procedural complications
GRAFT DYSFUNCTION
|
0.00%
0/24
|
2.0%
1/51
|
|
Injury, poisoning and procedural complications
INCISIONAL HERNIA
|
0.00%
0/24
|
2.0%
1/51
|
|
Injury, poisoning and procedural complications
POST PROCEDURAL HAEMORRHAGE
|
0.00%
0/24
|
2.0%
1/51
|
|
Injury, poisoning and procedural complications
WOUND DEHISCENCE
|
0.00%
0/24
|
2.0%
1/51
|
|
Investigations
BLOOD CREATININE INCREASED
|
16.7%
4/24
|
9.8%
5/51
|
|
Metabolism and nutrition disorders
HYPOGLYCAEMIA
|
0.00%
0/24
|
2.0%
1/51
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BASAL CELL CARCINOMA
|
0.00%
0/24
|
2.0%
1/51
|
|
Nervous system disorders
FACIAL NERVE DISORDER
|
0.00%
0/24
|
2.0%
1/51
|
|
Renal and urinary disorders
ACUTE PRERENAL FAILURE
|
0.00%
0/24
|
2.0%
1/51
|
|
Renal and urinary disorders
ANURIA
|
4.2%
1/24
|
0.00%
0/51
|
|
Renal and urinary disorders
NEPHROSCLEROSIS
|
4.2%
1/24
|
0.00%
0/51
|
|
Renal and urinary disorders
RENAL ARTERY STENOSIS
|
0.00%
0/24
|
2.0%
1/51
|
|
Renal and urinary disorders
RENAL FAILURE ACUTE
|
4.2%
1/24
|
2.0%
1/51
|
|
Renal and urinary disorders
URETERIC STENOSIS
|
0.00%
0/24
|
3.9%
2/51
|
|
Renal and urinary disorders
URINARY TRACT DISORDER
|
0.00%
0/24
|
2.0%
1/51
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA EXERTIONAL
|
0.00%
0/24
|
2.0%
1/51
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY ARTERIAL HYPERTENSION
|
4.2%
1/24
|
0.00%
0/51
|
|
Vascular disorders
ARTERIOVENOUS FISTULA
|
4.2%
1/24
|
2.0%
1/51
|
|
Vascular disorders
LYMPHOCELE
|
0.00%
0/24
|
2.0%
1/51
|
Other adverse events
| Measure |
Control Goup
n=24 participants at risk
During the pre-randomized treatment phase, all participants received a CNI-based regimen consisting of basiliximab, mycophenolic acid (MPA), cyclosporin A (CsA) and corticosteroids (optional). Upon randomization, participants in this group continued with a CNI-based regimen of MPA and CsA.
|
Everolimus Group
n=51 participants at risk
During the pre-randomized treatment phase, all participants received a CNI-based regimen consisting of basiliximab, mycophenolic acid (MPA), cyclosporin A (CsA) and corticosteroids (optional). Upon randomization, participants in this group made a stepwise switch to a CNI-free regimen of everolimus and MPA.
|
|---|---|---|
|
Blood and lymphatic system disorders
ANAEMIA
|
8.3%
2/24
|
11.8%
6/51
|
|
Blood and lymphatic system disorders
LEUKOPENIA
|
16.7%
4/24
|
39.2%
20/51
|
|
Gastrointestinal disorders
APHTHOUS STOMATITIS
|
0.00%
0/24
|
17.6%
9/51
|
|
Gastrointestinal disorders
CONSTIPATION
|
0.00%
0/24
|
5.9%
3/51
|
|
Gastrointestinal disorders
DIARRHOEA
|
0.00%
0/24
|
19.6%
10/51
|
|
Gastrointestinal disorders
FLATULENCE
|
0.00%
0/24
|
7.8%
4/51
|
|
Gastrointestinal disorders
NAUSEA
|
4.2%
1/24
|
5.9%
3/51
|
|
General disorders
OEDEMA PERIPHERAL
|
29.2%
7/24
|
25.5%
13/51
|
|
General disorders
PYREXIA
|
16.7%
4/24
|
9.8%
5/51
|
|
Infections and infestations
CYTOMEGALOVIRUS INFECTION
|
8.3%
2/24
|
7.8%
4/51
|
|
Infections and infestations
NASOPHARYNGITIS
|
4.2%
1/24
|
9.8%
5/51
|
|
Infections and infestations
URINARY TRACT INFECTION
|
25.0%
6/24
|
43.1%
22/51
|
|
Investigations
BLOOD CREATININE INCREASED
|
4.2%
1/24
|
9.8%
5/51
|
|
Metabolism and nutrition disorders
HYPERLIPIDAEMIA
|
4.2%
1/24
|
5.9%
3/51
|
|
Metabolism and nutrition disorders
HYPERURICAEMIA
|
4.2%
1/24
|
7.8%
4/51
|
|
Metabolism and nutrition disorders
HYPOCALCAEMIA
|
0.00%
0/24
|
5.9%
3/51
|
|
Metabolism and nutrition disorders
HYPOKALAEMIA
|
0.00%
0/24
|
23.5%
12/51
|
|
Metabolism and nutrition disorders
HYPOMAGNESAEMIA
|
4.2%
1/24
|
5.9%
3/51
|
|
Metabolism and nutrition disorders
HYPOPHOSPHATAEMIA
|
0.00%
0/24
|
7.8%
4/51
|
|
Metabolism and nutrition disorders
IRON DEFICIENCY
|
0.00%
0/24
|
9.8%
5/51
|
|
Metabolism and nutrition disorders
VITAMIN D DEFICIENCY
|
0.00%
0/24
|
5.9%
3/51
|
|
Psychiatric disorders
INSOMNIA
|
4.2%
1/24
|
5.9%
3/51
|
|
Renal and urinary disorders
PROTEINURIA
|
0.00%
0/24
|
15.7%
8/51
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
12.5%
3/24
|
5.9%
3/51
|
|
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION
|
0.00%
0/24
|
5.9%
3/51
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
8.3%
2/24
|
2.0%
1/51
|
|
Vascular disorders
HYPERTENSION
|
12.5%
3/24
|
11.8%
6/51
|
Additional Information
Study Director
Novartis Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER