Rapamycin Versus Mycophenolate Mofetil in Kidney-Pancreas Recipients

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

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: Mycophenolate Mofetil; Drug: Tacrolimus; Drug: Steroids; Drug: Rapamycin

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 170
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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; MMF 1 gm BID beginning 1st day postoperative day; Other Names: Cellcept; MMF; Drug: Tacrolimus; Part of standard maintenance.; Other Names: TAC; Drug: Steroids; Part of standard maintenance; Other Names: Corticosteroids
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: Tacrolimus; Part of standard maintenance.; Other Names: TAC; Drug: Steroids; Part of standard maintenance; Other Names: Corticosteroids; Drug: 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.; Other Names: Rapamune® (sirolimus)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Miami
• Collaborators: Astellas Pharma Inc
• Investigators: Principal Investigator: George W Burke, MD, University of Miami

Publications and helpful links

General 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2000
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: September 19, 2007
• First Submitted That Met QC Criteria: September 19, 2007
• First Posted (Estimate): September 21, 2007

Study Record Updates

• Last Update Posted (Actual): July 12, 2017
• Last Update Submitted That Met QC Criteria: June 12, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Rapamycin; Mycophenolate Mofetil (MMF); Kidney-Pancreas Transplant
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Tacrolimus; Mycophenolic Acid; Sirolimus
• Other Study ID Numbers: 20000176