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CompletedNCT00533442Updated Jul 12, 2017Results posted

Rapamycin Versus Mycophenolate Mofetil in Kidney-Pancreas Recipients

A Phase 2 interventional study of Rapamycin and Mycophenolate Mofetil in Type 1 Diabetes, sponsored by University of Miami. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2017-07-12.

Sponsored by University of Miami · Phase 2, Interventional, and Prevention

Phase
Phase 2
Study type
Interventional
Enrollment
170
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

This study was designed to determine which maintenance immunosuppressive agent, rapamycin or mycophenalate mofetil, resulted in better outcome in patients with type 1 diabetes and renal failure, who presented for a kidney-pancreas transplant.

Read the detailed description

This is a randomized, prospective single center study evaluating the two maintenance drugs above.

02

Conditions studied

  • Type 1 Diabetes

Keywords

  • Rapamycin
  • Mycophenolate Mofetil (MMF)
  • Kidney-Pancreas Transplant
03

In context

Diabetes Mellitus, Type 1

3,521 studies on the registry are indexed under Diabetes Mellitus, Type 1; 576 are open to participants now.

This study's enrollment of 170 is above the median of 40 across 2,648 interventional studies indexed under Diabetes Mellitus, Type 1.

Browse Diabetes Mellitus, Type 1 studies →

Lead sponsor

University of Miami is the lead sponsor of 820 studies on the registry; 161 are open to participants now.

Of its 111 completed or terminated interventional studies of FDA-regulated products, 93 (84%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Patient with Type 1 diabetes and end stage renal disease.
  • Women of childbearing potential must have had a negative pregnancy test (serum or urine).
  • Patient agrees to participate in the study and sign an informed consent.
  • Patient has no known contraindication to the administration of rapamycin or mycophenolate mofetil.
  • Patient has no history of hypersensitivity to rapamycin or mycophenolate mofetil.

Exclusion criteria

Exclusion Criteria:

  • Patient has history of a malignancy within two years, with the exception of adequately treated localized squamous or basal cell carcinoma of the skin without evidence of recurrence.
  • Patient is currently abusing drugs or alcohol.
  • Patient is known or suspected to have an active infection or be seropositive for hepatitis B surface antigen (HBsAg), hepatitis C (HCV) or human immunodeficiency virus (HIV).
05

Study design

Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
170 participants (actual)

Study arms

  • Active comparator
    Tacrolimus plus MMF plus Steroids

    Patients randomized to this arm were scheduled to receive maintenance therapy consisting of Tacrolimus, Mycophenolate Mofetil (MMF), and Steroids. Patients in both treatment arms received dual induction therapy consisting of Rabbit Anti-thymocyte Globulin (Thymoglobulin) plus Daclizumab.

    Drug: Mycophenolate Mofetil · Drug: Tacrolimus · Drug: Steroids

  • Experimental
    Tacrolimus plus Rapamycin plus Steroids

    Patients randomized to this arm were scheduled to receive maintenance therapy consisting of Tacrolimus, Rapamycin (Sirolimus), and Steroids. Patients in both treatment arms received dual induction therapy consisting of Rabbit Anti-thymocyte Globulin (Thymoglobulin) plus Daclizumab.

    Drug: Rapamycin · Drug: Tacrolimus · Drug: Steroids

Interventions

  • DrugRapamycin

    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.

    Also known as: Rapamune® (sirolimus)

  • DrugMycophenolate Mofetil

    MMF 1 gm BID beginning 1st day postoperative day

    Also known as: Cellcept, MMF

  • DrugTacrolimus

    Part of standard maintenance.

    Also known as: TAC

  • DrugSteroids

    Part of standard maintenance

    Also known as: Corticosteroids

06

What researchers measure

Primary outcomes

  1. Event-Specific Survival Comparisons

    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.

    Time frame: over 1-10 years post-transplant

Secondary outcomes

  1. Overall Kidney Transplant Function at 12, 36, and 60 Months Post-transplant.

    Comparisons of renal function (eGFR, measured in mL/min/1.73 m\^2) at 12, 36, and 60 months post-transplant.

    Time frame: at 1-5 years post-transplant

  2. Overall Pancreas Transplant Function at 12, 36, and 60 Months Post-transplant.

    Comparisons of pancreas function (C-peptide in ng/mL) at 12, 36, and 60 months post-transplant.

    Time frame: at 1-5 years post-transplant

07

Results

Posted Jul 12, 2017

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.

Allocation and Intent to Treat Analysis
Participant flow — Allocation and Intent to Treat Analysis
MilestoneTacrolimus Plus MMF Plus SteroidsTacrolimus Plus Rapamycin Plus Steroids
Started8684
Completed8684
Not completed00
Follow-up
Participant flow — Follow-up
MilestoneTacrolimus Plus MMF Plus SteroidsTacrolimus Plus Rapamycin Plus Steroids
Started8684
Completed7774
Not completed910

Outcome measures

PrimaryEvent-Specific Survival Comparisons

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.

Time frame:
over 1-10 years post-transplant
Reported as:
Count of participants · Participants
Event-Specific Survival Comparisons
ParticipantsTacrolimus Plus MMF Plus SteroidsTacrolimus Plus Rapamycin Plus Steroids
Biopsy-Proven Acute Rejection of the Kidney228
Biopsy-Proven Acute Rejection of the Pancreas91
Death-Censored Kidney Graft Failure1810
Death-Censored Pancreas Graft Failure72
Death-Uncensored Graft (Kidney&Pancreas) Survival2625
Patient Death1615
Statistical analysis
  • Tacrolimus Plus MMF Plus Steroids vs Tacrolimus Plus Rapamycin Plus Steroids · Log Rank · p = 0.01
  • Tacrolimus Plus MMF Plus Steroids vs Tacrolimus Plus Rapamycin Plus Steroids · Log Rank · p = 0.01
  • Tacrolimus Plus MMF Plus Steroids vs Tacrolimus Plus Rapamycin Plus Steroids · Log Rank · p = 0.16
  • Tacrolimus Plus MMF Plus Steroids vs Tacrolimus Plus Rapamycin Plus Steroids · Log Rank · p = 0.12
  • Tacrolimus Plus MMF Plus Steroids vs Tacrolimus Plus Rapamycin Plus Steroids · Log Rank · p = 0.96
  • Tacrolimus Plus MMF Plus Steroids vs Tacrolimus Plus Rapamycin Plus Steroids · Log Rank · p = >0.99 (Patient Death (logrank test).)
SecondaryOverall Kidney Transplant Function at 12, 36, and 60 Months Post-transplant.

Comparisons of renal function (eGFR, measured in mL/min/1.73 m\^2) at 12, 36, and 60 months post-transplant.

Time frame:
at 1-5 years post-transplant
Reported as:
Mean · mL/min/1.73m^2
Overall Kidney Transplant Function at 12, 36, and 60 Months Post-transplant.
mL/min/1.73m^2Tacrolimus Plus Rapamycin Plus SteroidsTacrolimus Plus MMF Plus Steroids
Mean eGFR at 12 months71.2 ± 2.467.2 ± 2.0
Mean eGFR at 36 months63.0 ± 3.161.5 ± 2.6
Mean eGFR at 60 months56.5 ± 4.161.9 ± 3.8
Statistical analysis
  • Tacrolimus Plus Rapamycin Plus Steroids vs Tacrolimus Plus MMF Plus Steroids · t-test, 2 sided · p = 0.21
  • Tacrolimus Plus Rapamycin Plus Steroids vs Tacrolimus Plus MMF Plus Steroids · t-test, 2 sided · p = 0.71
  • Tacrolimus Plus Rapamycin Plus Steroids vs Tacrolimus Plus MMF Plus Steroids · t-test, 2 sided · p = 0.33
SecondaryOverall Pancreas Transplant Function at 12, 36, and 60 Months Post-transplant.

Comparisons of pancreas function (C-peptide in ng/mL) at 12, 36, and 60 months post-transplant.

Time frame:
at 1-5 years post-transplant
Reported as:
Mean · ng/mL
Overall Pancreas Transplant Function at 12, 36, and 60 Months Post-transplant.
ng/mLTacrolimus Plus MMF Plus SteroidsTacrolimus Plus Rapamycin Plus Steroids
Mean Log {C-peptide at 12 months}1.15 ± 0.081.08 ± 0.07
Mean Log {C-peptide at 36 months}0.990 ± 0.080.986 ± 0.08
Mean Log {C-peptide at 60 months}1.17 ± 0.101.22 ± 0.10
Statistical analysis
  • Tacrolimus Plus MMF Plus Steroids vs Tacrolimus Plus Rapamycin Plus Steroids · t-test, 2 sided · p = .47
  • Tacrolimus Plus MMF Plus Steroids vs Tacrolimus Plus Rapamycin Plus Steroids · t-test, 2 sided · p = 0.97
  • Tacrolimus Plus MMF Plus Steroids vs Tacrolimus Plus Rapamycin Plus Steroids · t-test, 2 sided · p = 0.75

Adverse events

Collected over during the first year post-transplant. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Tacrolimus Plus MMF Plus Steroids16/86 (18.6%)40/86 (46.5%)3/86 (3.5%)
Tacrolimus Plus Rapamycin Plus Steroids15/84 (17.9%)38/84 (45.2%)5/84 (6%)
Most frequent serious events
Most frequent serious events
EventTacrolimus Plus MMF Plus SteroidsTacrolimus Plus Rapamycin Plus Steroids
InfectionInfections and infestations31/8632/84
Major Cardiovascular EventVascular disorders15/8611/84
Most frequent other events
Most frequent other events
EventTacrolimus Plus MMF Plus SteroidsTacrolimus Plus Rapamycin Plus Steroids
New Onset Diabetes Mellitus Type 2 after Transplant (NODAT)Endocrine disorders3/865/84

Baseline characteristics

Age, Continuous
Age, Continuous(years)Tacrolimus Plus MMF Plus SteroidsTacrolimus Plus Rapamycin Plus SteroidsTotal
Mean43.4 ± 9.341.5 ± 8.242.5 ± 8.8
Sex: Female, Male
Sex: Female, Male(Participants)Tacrolimus Plus MMF Plus SteroidsTacrolimus Plus Rapamycin Plus SteroidsTotal
Female313465
Male5550105
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Tacrolimus Plus MMF Plus SteroidsTacrolimus Plus Rapamycin Plus SteroidsTotal
Caucasian5547102
Hispanic193150
African-American11617
Other101
08

Study locations

1 site
  • University of Miami, Miller School of Medicine
    Miami, Florida 33136, United States
09

References and documents

Publications

  • Burke GW 3rd, Ciancio G, Figueiro J, Olson L, Gomez C, Rosen A, Suzart K, Miller J. Steroid-resistant acute rejection following SPK: importance of maintaining therapeutic dosing in a triple-drug regimen. Transplant Proc. 2002 Aug;34(5):1918-9. doi: 10.1016/s0041-1345(02)03122-6. No abstract available. PubMed 12176628 ↗
  • Burke G 3rd, Ciancio G, Figueiro J, Olson L, Gomez C, Rosen A, Suzart K, Miller J. Can acute rejection be prevented in SPK transplantation? Transplant Proc. 2002 Aug;34(5):1913-4. doi: 10.1016/s0041-1345(02)03149-4. No abstract available. PubMed 12176626 ↗
  • Burke GW 3rd, Ciancio G, Figueiro J, Buigas R, Olson L, Roth D, Kupin W, Miller J. Hypercoagulable state associated with kidney-pancreas transplantation. Thromboelastogram-directed anti-coagulation and implications for future therapy. Clin Transplant. 2004 Aug;18(4):423-8. doi: 10.1111/j.1399-0012.2004.00183.x. PubMed 15233820 ↗
  • Ciancio G, Sageshima J, Chen L, Gaynor JJ, Hanson L, Tueros L, Montenora-Velarde E, Gomez C, Kupin W, Guerra G, Mattiazzi A, Fornoni A, Pugliese A, Roth D, Wolf M, Burke GW 3rd. Advantage of rapamycin over mycophenolate mofetil when used with tacrolimus for simultaneous pancreas kidney transplants: randomized, single-center trial at 10 years. Am J Transplant. 2012 Dec;12(12):3363-76. doi: 10.1111/j.1600-6143.2012.04235.x. Epub 2012 Sep 4. PubMed 22946986 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 12, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00533442
Lead sponsor
University of Miami
Collaborators
Astellas Pharma Inc
Responsible party
George W. Burke (Professor of Surgery, University of Miami) — Principal investigator
First posted
Sep 21, 2007
Start date
Sep 2000
Primary completion
May 2016
Completion
May 2016
Results posted
Jul 12, 2017
Last update
Jul 12, 2017

Study contacts

George W Burke, MD
principal investigator · University of Miami

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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