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

Study Overview
=================
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.

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

Conditions
-----------------
Kidney Diseases

Intervention / Treatment
-----------------
* Drug: Anti-thymocyte globulin
* Drug: Mycophenolate mofetil
* Drug: Prednisone
* Drug: Tacrolimus
* Drug: Sirolimus


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GFR (iothalamate clearance) at other time points |  | 24 months | 
| Other measures of renal function (serum creatinine, proteinuria and albuminuria) |  | 24 months | 
| Acute rejection both early and after tacrolimus withdrawal |  | 24 months | 
| Patient and graft survival |  | 24 months after transplantation | 
| Complications-especially hypertension, diabetes, dyslipidemia |  | 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
kidney transplantation, immunosuppression, calcineurin inhibitor, sirolimus, chronic allograft nephropathy