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

Kidney Diseases Clinical Trial

Official title:

A Prospective, Randomized Trial of Calcineurin-Inhibitor Withdrawal in Renal Allograft Recipients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00275535
• Other study ID #: 124-01
• Status: Completed
• Phase: Phase 4
• First received: January 10, 2006
• Last updated: December 6, 2011
• Start date: April 2001
• Est. completion date: December 2008

Study information

• Verified date: December 2011
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 165
• Est. completion date: December 2008
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Diseases

Intervention

Drug:
• Anti-thymocyte globulin
Thymoglobulin 1.5 mg/kg/d (days 0,1,2,4,6)
• Mycophenolate mofetil
Mycophenolate mofetil 750 mg p.o. b.i.d.- maintenance
• Prednisone
Prednisone 500 mg/day initially, tapered to 5 mg/day by day 92
• Tacrolimus
Tacrolimus - maintain trough levels of 6-8 ng/ml (whole blood Imx assay)
• Sirolimus
Rapamycin 3 to 5 mg/day; adjust to the high-performance liquid chromatography (HPLC) blood level 15 to 20 ng ml

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (4)

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

Country where clinical trial is conducted

United States, 

References & Publications (2)

Dean PG, Grande JP, Sethi S, Park WD, Griffin MD, Cosio FG, Larson TS, Stegall MD. Kidney transplant histology after one year of continuous therapy with sirolimus compared with tacrolimus. Transplantation. 2008 Apr 27;85(8):1212-5. doi: 10.1097/TP.0b013e3 — View Citation

Larson TS, Dean PG, Stegall MD, Griffin MD, Textor SC, Schwab TR, Gloor JM, Cosio FG, Lund WJ, Kremers WK, Nyberg SL, Ishitani MB, Prieto M, Velosa JA. Complete avoidance of calcineurin inhibitors in renal transplantation: a randomized trial comparing sir — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glomerular filtration rate (GFR) (iothalamate clearance) at 12 months following transplantation	Glomerular filtration rate (Iothalamate clearance) at 12 months following transplantation.	12 months following transplantation	No
Secondary	GFR (iothalamate clearance) at other time points		24 months	No
Secondary	Other measures of renal function (serum creatinine, proteinuria and albuminuria)		24 months	No
Secondary	Acute rejection both early and after tacrolimus withdrawal		24 months	No
Secondary	Patient and graft survival		24 months after transplantation	No
Secondary	Complications-especially hypertension, diabetes, dyslipidemia		24 months	No

External Links

•   Mayo Clinic Clinical Trials