Rapamycin Versus Mycophenolate Mofetil in Kidney-Pancreas Recipients

Study Overview
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Brief Summary
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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.

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

Official Title
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Tacrolimus and Mycophenolate Mofetil vs Tacrolimus and Sirolimus in SPK, Pancreas After Kidney or Pancreas Transplant Alone

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Drug: Rapamycin
* Drug: Mycophenolate Mofetil
* Drug: Tacrolimus
* Drug: Steroids


Participation Criteria
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Eligibility Criteria
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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: 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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tacrolimus plus MMF plus Steroids<br>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<br>* MMF 1 gm BID beginning 1st day postoperative day<br>* Other names: MMF;Drug: Tacrolimus<br>* Part of standard maintenance.<br>* Other names: TAC;Drug: Steroids<br>* Part of standard maintenance<br>* Other names: Corticosteroids;|
| Experimental: Tacrolimus plus Rapamycin plus Steroids<br>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<br>* 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.<br>* Other names: Rapamune® (sirolimus);Drug: Tacrolimus<br>* Part of standard maintenance.<br>* Other names: TAC;Drug: Steroids<br>* Part of standard maintenance<br>* Other names: Corticosteroids;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | over 1-10 years post-transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | at 1-5 years post-transplant | 
| 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. | at 1-5 years post-transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rapamycin, Mycophenolate Mofetil (MMF), Kidney-Pancreas Transplant