Clinical trial NCT00275535: The Comparison of Tacrolimus and Sirolimus Immunosuppression Based Drug Regimens in Kidney Transplant Recipients
Official title: A Prospective, Randomized Trial of Calcineurin-Inhibitor Withdrawal in Renal Allograft Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Kidney Diseases
Keywords: kidney transplantation
immunosuppression
calcineurin inhibitor
sirolimus
chronic allograft nephropathy
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: Wyeth is now a wholly owned subsidiary of Pfizer
name: Genzyme, a Sanofi Company
name: Roche Pharma AG
First posted: 2006-01-12
Enrollment: 165
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Glomerular filtration rate (GFR) (iothalamate clearance) at 12 months following transplantation
timeFrame: 12 months following transplantation
Secondary outcomes:
measure: GFR (iothalamate clearance) at other time points
timeFrame: 24 months
measure: Other measures of renal function (serum creatinine, proteinuria and albuminuria)
timeFrame: 24 months
measure: Acute rejection both early and after tacrolimus withdrawal
timeFrame: 24 months
measure: Patient and graft survival
timeFrame: 24 months after transplantation
measure: Complications-especially hypertension, diabetes, dyslipidemia
timeFrame: 24 months
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Mark D. Stegall, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.0b013e31816a8ae6.
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 sirolimus and tacrolimus. Am J Transplant. 2006 Mar;6(3):514-22. doi: 10.1111/j.1600-6143.2005.01177.x.