The Comparison of Tacrolimus and Sirolimus Immunosuppression Based Drug Regimens in Kidney Transplant Recipients

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT00275535
• Collaborator: Wyeth is now a wholly owned subsidiary of Pfizer (Industry), Genzyme, a Sanofi Company (Industry), Roche Pharma AG (Industry)
• Enrollment: 165
• Location: 1
• Arms: 2
• Duration (Months): 92
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

This study was done to find out which treatment, tacrolimus or sirolimus, leads to better long-term kidney function in kidney transplant patients.

Condition or Disease	Intervention/Treatment	Phase
Kidney Diseases	Drug: Anti-thymocyte globulin; Drug: Mycophenolate mofetil; Drug: Prednisone; Drug: Tacrolimus; Drug: Sirolimus	Phase 4

Detailed Description

The aim of this study was to compare the complete avoidance of calcineurin inhibitors (CI) using a sirolimus-based immunosuppressive regimen to a tacrolimus-based regimen in kidney transplantation. This study was a prospective open-label trial randomizing patients to receive tacrolimus, mycophenolate mofetil and prednisone or sirolimus, mycophenolate mofetil and prednisone. All patients received antithymocyte globulin induction. All rejection episodes were proven by biopsy. The hypothesis was that CI free immunosuppression after kidney transplantation will lead to an increase in glomerular filtration rate (GFR) at one year after kidney transplantation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 165 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Randomized Trial of Calcineurin-Inhibitor Withdrawal in Renal Allograft Recipients
• Study Start Date: Apr 1, 2001
• Actual Primary Completion Date: Nov 1, 2007
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Tacrolimus Calcineurin inhibitor arm, consisting of treatment with tacrolimus, mycophenolate mofetil, and prednisone.	Drug: Anti-thymocyte globulin; Thymoglobulin 1.5 mg/kg/d (days 0,1,2,4,6); Other Names: Thymoglobulin Atgam ; Drug: Mycophenolate mofetil; Mycophenolate mofetil 750 mg p.o. b.i.d.- maintenance; Other Names: CellCept ; Drug: Prednisone; Prednisone 500 mg/day initially, tapered to 5 mg/day by day 92; Other Names: Deltasone Liquid Pred Meticorten Orasone Prednicen-M Prednicot Sterapred Sterapred DS ; Drug: Tacrolimus; Tacrolimus - maintain trough levels of 6-8 ng/ml (whole blood Imx assay); Other Names: Prograf Advagraf Protopic
Active Comparator: Sirolimus Calcineurin inhibitor-free arm, consisting of treatment with rapamycin, mycophenolate mofetil, and prednisone.	Drug: Anti-thymocyte globulin; Thymoglobulin 1.5 mg/kg/d (days 0,1,2,4,6); Other Names: Thymoglobulin Atgam ; Drug: Mycophenolate mofetil; Mycophenolate mofetil 750 mg p.o. b.i.d.- maintenance; Other Names: CellCept ; Drug: Prednisone; Prednisone 500 mg/day initially, tapered to 5 mg/day by day 92; Other Names: Deltasone Liquid Pred Meticorten Orasone Prednicen-M Prednicot Sterapred Sterapred DS ; Drug: Sirolimus; Rapamycin 3 to 5 mg/day; adjust to the high-performance liquid chromatography (HPLC) blood level 15 to 20 ng ml; Other Names: Rapamune

Outcome Measures

Primary Outcome Measures

1. Glomerular filtration rate (GFR) (iothalamate clearance) at 12 months following transplantation [12 months following transplantation]

   Glomerular filtration rate (Iothalamate clearance) at 12 months following transplantation.

Secondary Outcome Measures

1. GFR (iothalamate clearance) at other time points [24 months]

2. Other measures of renal function (serum creatinine, proteinuria and albuminuria) [24 months]

3. Acute rejection both early and after tacrolimus withdrawal [24 months]

4. Patient and graft survival [24 months after transplantation]

5. Complications-especially hypertension, diabetes, dyslipidemia [24 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Living and deceased donor kidney transplant recipients at the Mayo Clinic, Rochester, Minnesota

Exclusion Criteria:

• Patients with type 1 diabetes less than 50 years of age who receive a living donor kidney transplant followed by a pancreas transplant

• Pediatric patients (<18 years of age)

• Multi-organ transplants (e.g., kidney-pancreas, kidney-liver)

• ABO-incompatible or positive crossmatch recipients (ABO incompatibility is an immune system reaction that occurs when blood from two different and incompatible blood types are mixed together.)

• Patients with severe hyperlipidemia (serum cholesterol >350 mg/dl or serum triglycerides >500 mg/dl

• Patients with severe leukopenia (White Blood Cell count [WBC]<3000 10^3/ml)

• Patients unwilling to return to the transplant center for late follow-up visits

• Body mass index (BMI) ≥ 32 with incisional problems post transplant (as determined by renal transplant surgeon

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic
• Wyeth is now a wholly owned subsidiary of Pfizer
• Genzyme, a Sanofi Company
• Roche Pharma AG

Investigators

• Principal Investigator: Mark D. Stegall, M.D., Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Mayo Clinic Clinical Trials

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00275535
• Other Study ID Numbers: 124-01
• First Posted: Jan 12, 2006
• Last Update Posted: Dec 8, 2011
• Last Verified: Dec 1, 2011

• Keywords provided by , ,: kidney transplantation; immunosuppression; calcineurin inhibitor; sirolimus; chronic allograft nephropathy
• Additional relevant MeSH terms: Kidney Diseases; Mycophenolic Acid; Sirolimus; Prednisone; Tacrolimus; Thymoglobulin; Antilymphocyte Serum

Study Results

No Results Posted as of Dec 8, 2011