Trial Outcomes & Findings for Rapamycin Versus Mycophenolate Mofetil in Kidney-Pancreas Recipients (NCT NCT00533442)
NCT ID: NCT00533442
Last Updated: 2017-07-12
Results Overview
Freedom from biopsy-proven acute rejection of the kidney allograft; Freedom from biopsy-proven acute rejection of the pancreas allograft; Death-censored kidney graft survival; Death-censored pancreas graft survival; Death-uncensored graft (kidney and pancreas) survival; and Patient survival.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
170 participants
Primary outcome timeframe
over 1-10 years post-transplant
Results posted on
2017-07-12
Participant Flow
From September 1, 2000 through December 15, 2009, 170 consecutive patients with type 1 diabetes and ESRD were randomized to receive either Rapamycin (N=84) or MMF (N=86) immediately prior to transplant. Post-transplant clinical follow-up of patients continued through January 15, 2011.
A randomized block design was implemented for the randomization scheme using Proc Plan in SAS. Patients were randomly assigned (allocation ratio of 1:1) to the two treatment arms in blocks of 4 and 6 patients (block sizes were also chosen randomly), ensuring a balance of patients across treatment arms after each block of patients was randomized.
Participant milestones
| Measure |
Tacrolimus Plus MMF Plus Steroids
This group of kidney-pancreas recipients was randomized to receive mycophenolate mofetil and tacrolimus after transplantation.
Tacrolimus and mycophenolate mofetil: MMF 1 gm BID beginning 1st day postoperative day
|
Tacrolimus Plus Rapamycin Plus Steroids
Patients randomized to this arm received Sirolimus, after kidney-pancreas transplantation.
Rapamycin: Rapamycin was initiated on day 1 postoperatively, 4mg/day;levels were maintained 5-8ng/ml. Those patients randomized to receive mycophenolate mofetil were given 1gm twice/day starting on the first post-operative day.
Rapamune and Tacrolimus: Sirolimus 2 mg/day beginning 1st postoperative day (trough target levels:
10-15ng/ml)
Mycophenolate Mofetil: Patients randomized to receive mycophenolate mofetil were given 1gm twice/day starting on the first post-operative day.
|
|---|---|---|
|
Allocation and Intent to Treat Analysis
STARTED
|
86
|
84
|
|
Allocation and Intent to Treat Analysis
COMPLETED
|
86
|
84
|
|
Allocation and Intent to Treat Analysis
NOT COMPLETED
|
0
|
0
|
|
Follow-up
STARTED
|
86
|
84
|
|
Follow-up
COMPLETED
|
77
|
74
|
|
Follow-up
NOT COMPLETED
|
9
|
10
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Rapamycin Versus Mycophenolate Mofetil in Kidney-Pancreas Recipients
Baseline characteristics by cohort
| Measure |
Tacrolimus Plus MMF Plus Steroids
n=86 Participants
This group of kidney-pancreas recipients was randomized to receive mycophenolate mofetil and tacrolimus after transplantation.
Tacrolimus and mycophenolate mofetil: MMF 1 gm BID beginning 1st day postoperative day
|
Tacrolimus Plus Rapamycin Plus Steroids
n=84 Participants
Patients randomized to this arm received Sirolimus, after kidney-pancreas transplantation.
Rapamycin: Rapamycin was initiated on day 1 postoperatively, 4mg/day;levels were maintained 5-8ng/ml. Those patients randomized to receive mycophenolate mofetil were given 1gm twice/day starting on the first post-operative day.
Rapamune and Tacrolimus: Sirolimus 2 mg/day beginning 1st postoperative day (trough target levels:
10-15ng/ml)
Mycophenolate Mofetil: Patients randomized to receive mycophenolate mofetil were given 1gm twice/day starting on the first post-operative day.
|
Total
n=170 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
43.4 years
STANDARD_DEVIATION 9.3 • n=93 Participants
|
41.5 years
STANDARD_DEVIATION 8.2 • n=4 Participants
|
42.5 years
STANDARD_DEVIATION 8.8 • n=27 Participants
|
|
Sex: Female, Male
Female
|
31 Participants
n=93 Participants
|
34 Participants
n=4 Participants
|
65 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
55 Participants
n=93 Participants
|
50 Participants
n=4 Participants
|
105 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
55 Participants
n=93 Participants
|
47 Participants
n=4 Participants
|
102 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
19 Participants
n=93 Participants
|
31 Participants
n=4 Participants
|
50 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
African-American
|
11 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
17 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: over 1-10 years post-transplantFreedom from biopsy-proven acute rejection of the kidney allograft; Freedom from biopsy-proven acute rejection of the pancreas allograft; Death-censored kidney graft survival; Death-censored pancreas graft survival; Death-uncensored graft (kidney and pancreas) survival; and Patient survival.
Outcome measures
| Measure |
Tacrolimus Plus MMF Plus Steroids
n=86 Participants
This group of kidney-pancreas recipients was randomized to receive mycophenolate mofetil and tacrolimus after transplantation.
Tacrolimus and mycophenolate mofetil: MMF 1 gm BID beginning 1st day postoperative day
|
Tacrolimus Plus Rapamycin Plus Steroids
n=84 Participants
Patients randomized to this arm received Sirolimus, after kidney-pancreas transplantation.
Rapamycin: Rapamycin was initiated on day 1 postoperatively, 4mg/day;levels were maintained 5-8ng/ml. Those patients randomized to receive mycophenolate mofetil were given 1gm twice/day starting on the first post-operative day.
Rapamune and Tacrolimus: Sirolimus 2 mg/day beginning 1st postoperative day (trough target levels:
10-15ng/ml)
Mycophenolate Mofetil: Patients randomized to receive mycophenolate mofetil were given 1gm twice/day starting on the first post-operative day.
|
|---|---|---|
|
Event-Specific Survival Comparisons
Biopsy-Proven Acute Rejection of the Kidney
|
22 Participants
|
8 Participants
|
|
Event-Specific Survival Comparisons
Biopsy-Proven Acute Rejection of the Pancreas
|
9 Participants
|
1 Participants
|
|
Event-Specific Survival Comparisons
Death-Censored Kidney Graft Failure
|
18 Participants
|
10 Participants
|
|
Event-Specific Survival Comparisons
Death-Censored Pancreas Graft Failure
|
7 Participants
|
2 Participants
|
|
Event-Specific Survival Comparisons
Death-Uncensored Graft (Kidney&Pancreas) Survival
|
26 Participants
|
25 Participants
|
|
Event-Specific Survival Comparisons
Patient Death
|
16 Participants
|
15 Participants
|
SECONDARY outcome
Timeframe: at 1-5 years post-transplantPopulation: Number analyzed here includes all patients alive with a functioning graft that had an available measurement taken at that time
Comparisons of renal function (eGFR, measured in mL/min/1.73 m\^2) at 12, 36, and 60 months post-transplant.
Outcome measures
| Measure |
Tacrolimus Plus MMF Plus Steroids
n=84 Participants
This group of kidney-pancreas recipients was randomized to receive mycophenolate mofetil and tacrolimus after transplantation.
Tacrolimus and mycophenolate mofetil: MMF 1 gm BID beginning 1st day postoperative day
|
Tacrolimus Plus Rapamycin Plus Steroids
n=86 Participants
Patients randomized to this arm received Sirolimus, after kidney-pancreas transplantation.
Rapamycin: Rapamycin was initiated on day 1 postoperatively, 4mg/day;levels were maintained 5-8ng/ml. Those patients randomized to receive mycophenolate mofetil were given 1gm twice/day starting on the first post-operative day.
Rapamune and Tacrolimus: Sirolimus 2 mg/day beginning 1st postoperative day (trough target levels:
10-15ng/ml)
Mycophenolate Mofetil: Patients randomized to receive mycophenolate mofetil were given 1gm twice/day starting on the first post-operative day.
|
|---|---|---|
|
Overall Kidney Transplant Function at 12, 36, and 60 Months Post-transplant.
Mean eGFR at 12 months
|
71.2 mL/min/1.73m^2
Standard Error 2.4
|
67.2 mL/min/1.73m^2
Standard Error 2.0
|
|
Overall Kidney Transplant Function at 12, 36, and 60 Months Post-transplant.
Mean eGFR at 36 months
|
63.0 mL/min/1.73m^2
Standard Error 3.1
|
61.5 mL/min/1.73m^2
Standard Error 2.6
|
|
Overall Kidney Transplant Function at 12, 36, and 60 Months Post-transplant.
Mean eGFR at 60 months
|
56.5 mL/min/1.73m^2
Standard Error 4.1
|
61.9 mL/min/1.73m^2
Standard Error 3.8
|
SECONDARY outcome
Timeframe: at 1-5 years post-transplantPopulation: Number analyzed here includes all patients alive with a functioning graft that had an available measurement taken at that time
Comparisons of pancreas function (C-peptide in ng/mL) at 12, 36, and 60 months post-transplant.
Outcome measures
| Measure |
Tacrolimus Plus MMF Plus Steroids
n=86 Participants
This group of kidney-pancreas recipients was randomized to receive mycophenolate mofetil and tacrolimus after transplantation.
Tacrolimus and mycophenolate mofetil: MMF 1 gm BID beginning 1st day postoperative day
|
Tacrolimus Plus Rapamycin Plus Steroids
n=84 Participants
Patients randomized to this arm received Sirolimus, after kidney-pancreas transplantation.
Rapamycin: Rapamycin was initiated on day 1 postoperatively, 4mg/day;levels were maintained 5-8ng/ml. Those patients randomized to receive mycophenolate mofetil were given 1gm twice/day starting on the first post-operative day.
Rapamune and Tacrolimus: Sirolimus 2 mg/day beginning 1st postoperative day (trough target levels:
10-15ng/ml)
Mycophenolate Mofetil: Patients randomized to receive mycophenolate mofetil were given 1gm twice/day starting on the first post-operative day.
|
|---|---|---|
|
Overall Pancreas Transplant Function at 12, 36, and 60 Months Post-transplant.
Mean Log {C-peptide at 36 months}
|
0.990 ng/mL
Standard Error 0.08
|
0.986 ng/mL
Standard Error 0.08
|
|
Overall Pancreas Transplant Function at 12, 36, and 60 Months Post-transplant.
Mean Log {C-peptide at 12 months}
|
1.15 ng/mL
Standard Error 0.08
|
1.08 ng/mL
Standard Error 0.07
|
|
Overall Pancreas Transplant Function at 12, 36, and 60 Months Post-transplant.
Mean Log {C-peptide at 60 months}
|
1.17 ng/mL
Standard Error 0.10
|
1.22 ng/mL
Standard Error 0.10
|
Adverse Events
Tacrolimus Plus MMF Plus Steroids
Serious events: 40 serious events
Other events: 3 other events
Deaths: 16 deaths
Tacrolimus Plus Rapamycin Plus Steroids
Serious events: 38 serious events
Other events: 5 other events
Deaths: 15 deaths
Serious adverse events
| Measure |
Tacrolimus Plus MMF Plus Steroids
n=86 participants at risk
This group of kidney-pancreas recipients was randomized to receive mycophenolate mofetil and tacrolimus after transplantation.
Tacrolimus and mycophenolate mofetil: MMF 1 gm BID beginning 1st day postoperative day
|
Tacrolimus Plus Rapamycin Plus Steroids
n=84 participants at risk
Patients randomized to this arm received Sirolimus, after kidney-pancreas transplantation.
Rapamycin: Rapamycin was initiated on day 1 postoperatively, 4mg/day;levels were maintained 5-8ng/ml. Those patients randomized to receive mycophenolate mofetil were given 1gm twice/day starting on the first post-operative day.
Rapamune and Tacrolimus: Sirolimus 2 mg/day beginning 1st postoperative day (trough target levels:
10-15ng/ml)
Mycophenolate Mofetil: Patients randomized to receive mycophenolate mofetil were given 1gm twice/day starting on the first post-operative day.
|
|---|---|---|
|
Infections and infestations
Infection
|
36.0%
31/86 • Number of events 31 • during the first year post-transplant
Serious Adverse Events were defined as: 1) the occurrence of any infection that required hospitalization, and 2) a major cardiovascular event.
|
38.1%
32/84 • Number of events 32 • during the first year post-transplant
Serious Adverse Events were defined as: 1) the occurrence of any infection that required hospitalization, and 2) a major cardiovascular event.
|
|
Vascular disorders
Major Cardiovascular Event
|
17.4%
15/86 • Number of events 15 • during the first year post-transplant
Serious Adverse Events were defined as: 1) the occurrence of any infection that required hospitalization, and 2) a major cardiovascular event.
|
13.1%
11/84 • Number of events 11 • during the first year post-transplant
Serious Adverse Events were defined as: 1) the occurrence of any infection that required hospitalization, and 2) a major cardiovascular event.
|
Other adverse events
| Measure |
Tacrolimus Plus MMF Plus Steroids
n=86 participants at risk
This group of kidney-pancreas recipients was randomized to receive mycophenolate mofetil and tacrolimus after transplantation.
Tacrolimus and mycophenolate mofetil: MMF 1 gm BID beginning 1st day postoperative day
|
Tacrolimus Plus Rapamycin Plus Steroids
n=84 participants at risk
Patients randomized to this arm received Sirolimus, after kidney-pancreas transplantation.
Rapamycin: Rapamycin was initiated on day 1 postoperatively, 4mg/day;levels were maintained 5-8ng/ml. Those patients randomized to receive mycophenolate mofetil were given 1gm twice/day starting on the first post-operative day.
Rapamune and Tacrolimus: Sirolimus 2 mg/day beginning 1st postoperative day (trough target levels:
10-15ng/ml)
Mycophenolate Mofetil: Patients randomized to receive mycophenolate mofetil were given 1gm twice/day starting on the first post-operative day.
|
|---|---|---|
|
Endocrine disorders
New Onset Diabetes Mellitus Type 2 after Transplant (NODAT)
|
3.5%
3/86 • Number of events 3 • during the first year post-transplant
Serious Adverse Events were defined as: 1) the occurrence of any infection that required hospitalization, and 2) a major cardiovascular event.
|
6.0%
5/84 • Number of events 5 • during the first year post-transplant
Serious Adverse Events were defined as: 1) the occurrence of any infection that required hospitalization, and 2) a major cardiovascular event.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place