Safety/Efficacy of Induction Agents With Tacrolimus, MMF, and Rapid Steroid Withdrawal in Renal Transplant Recipients

Phase 4

Completed

• Conditions: Kidney Transplantation
• Interventions: Drug: tacrolimus; Drug: rabbit anti-thymocyte globulin; Drug: basiliximab; Drug: alemtuzumab; Drug: mycophenolate mofetil; Drug: steroids

• Registration Number: NCT00113269
• Lead Sponsor: Astellas Pharma Inc

Brief Summary

The purpose of this study is to compare the safety and efficacy of different induction agents (alemtuzumab, basiliximab or rabbit anti-thymocyte globulin) in renal transplant recipients treated with tacrolimus, mycophenolate mofetil (MMF) and a rapid steroid withdrawal.

Detailed Description

A 2 arm (1 Active, 1 Active Control) study is to compare the safety and efficacy of different induction agents (alemtuzumab, basiliximab or rabbit anti-thymocyte globulin) in renal transplant recipients treated with tacrolimus, MMF and a rapid steroid withdrawal.

Study Timeline

• Study Start: 2005-05
• Study First Submitted: 2005-06-07
• Study First Submitted QC: 2005-06-07
• Study First Posted: 2005-06-08
• Primary Completion: 2009-03
• Study Completion: 2009-03
• Results First Submitted: 2011-06-07
• Results First Submitted QC: 2011-06-07
• Results First Posted: 2011-07-08
• Status Verified: 2011-08
• Last Update Submitted: 2011-08-09
• Last Update Posted: 2011-08-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 501

Inclusion Criteria

• Recipient of a primary or re-transplanted deceased donor kidney or a primary or re-transplanted non-human leukocyte antigen (HLA) living donor kidney (ie., HLA identical or 0 antigen mismatch deceased donor kidneys are allowed).

Exclusion Criteria

• Patient has previously received an organ transplant other than a kidney
• Patient receiving chronic steroid therapy at time of transplant

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Alemtuzumab High-Risk Patients	tacrolimus	Alemtuzumab, tacrolimus, mycophenolate mofetil and steroids; High risk patients: Panel reactive antibody ≥ 20% or re-transplant or African American
Alemtuzumab High-Risk Patients	steroids	Alemtuzumab, tacrolimus, mycophenolate mofetil and steroids; High risk patients: Panel reactive antibody ≥ 20% or re-transplant or African American
Conventional High-Risk Patients	rabbit anti-thymocyte globulin	Rabbit anti-thymocyte globulin, tacrolimus, mycophenolate mofetil and steroids; High risk patients: Panel reactive antibody ≥ 20% or re-transplant or African American
Conventional High-Risk Patients	steroids	Rabbit anti-thymocyte globulin, tacrolimus, mycophenolate mofetil and steroids; High risk patients: Panel reactive antibody ≥ 20% or re-transplant or African American
Alemtuzumab Low- Risk Patients	steroids	Alemtuzumab, tacrolimus, mycophenolate mofetil and steroids; Low risk patients: Panel reactive antibody \< 20% and first transplant and non-African American
Conventional Low-Risk Patients	steroids	Basiliximab, tacrolimus, mycophenolate mofetil and steroids; Low risk patients: Panel reactive antibody \< 20% and first transplant and non-African American
Alemtuzumab High-Risk Patients	alemtuzumab	Alemtuzumab, tacrolimus, mycophenolate mofetil and steroids; High risk patients: Panel reactive antibody ≥ 20% or re-transplant or African American
Alemtuzumab High-Risk Patients	mycophenolate mofetil	Alemtuzumab, tacrolimus, mycophenolate mofetil and steroids; High risk patients: Panel reactive antibody ≥ 20% or re-transplant or African American
Conventional High-Risk Patients	tacrolimus	Rabbit anti-thymocyte globulin, tacrolimus, mycophenolate mofetil and steroids; High risk patients: Panel reactive antibody ≥ 20% or re-transplant or African American
Conventional High-Risk Patients	mycophenolate mofetil	Rabbit anti-thymocyte globulin, tacrolimus, mycophenolate mofetil and steroids; High risk patients: Panel reactive antibody ≥ 20% or re-transplant or African American
Alemtuzumab Low- Risk Patients	tacrolimus	Alemtuzumab, tacrolimus, mycophenolate mofetil and steroids; Low risk patients: Panel reactive antibody \< 20% and first transplant and non-African American
Alemtuzumab Low- Risk Patients	alemtuzumab	Alemtuzumab, tacrolimus, mycophenolate mofetil and steroids; Low risk patients: Panel reactive antibody \< 20% and first transplant and non-African American
Alemtuzumab Low- Risk Patients	mycophenolate mofetil	Alemtuzumab, tacrolimus, mycophenolate mofetil and steroids; Low risk patients: Panel reactive antibody \< 20% and first transplant and non-African American
Conventional Low-Risk Patients	tacrolimus	Basiliximab, tacrolimus, mycophenolate mofetil and steroids; Low risk patients: Panel reactive antibody \< 20% and first transplant and non-African American
Conventional Low-Risk Patients	basiliximab	Basiliximab, tacrolimus, mycophenolate mofetil and steroids; Low risk patients: Panel reactive antibody \< 20% and first transplant and non-African American
Conventional Low-Risk Patients	mycophenolate mofetil	Basiliximab, tacrolimus, mycophenolate mofetil and steroids; Low risk patients: Panel reactive antibody \< 20% and first transplant and non-African American

Primary Outcome Measures

Name	Time	Method
Patient Incidence of Biopsy-confirmed Acute Rejection (BCAR) at 6 Months	6 months	A BCAR is a suspected new rejection w/in 6 mos. of skin closure, confirmed by Banff Grade ≥1A assigned by a pathologist. The Banff 97 classification system is used for interpreting histology of allograft biopsies, including Mild (1A/1B), Moderate (2A/2B) \& Severe (3).; Kaplan Meier analysis was used to estimate % of pts. w/event. Patients w/no event at time of scheduled visit or whose 1st event was after premature discontinuation of study drug/tacrolimus were censored on the scheduled day of a) assessment, b) of premature treatment discontinuation or c) last evaluation, whichever came 1st.

Secondary Outcome Measures

Name	Time	Method
Overall Patient Incidence of BCAR	End of Study (36 months)	Overall patient incidence of BCAR is defined as a suspected new rejection at any time following skin closure confirmed by a Banff Grade ≥ 1A as assigned by a local pathologist. Incidence is reported as the percentage of patients with BCAR. The Banff 97 scale is a classification system for interpreting histology of allograft biopsies. The grades range from Mild (1A \& 1B) to Moderate (2A \& 2B) to Severe (3).; End of Study was defined as the last day of evaluation and could have included bivariate assessments after 36 months.
Efficacy Failure	End of Study (36 months)	Efficacy Failure is a composite measure of biopsy confirmed acute rejection, graft loss and death. Data is reported as the percentage of patients with Efficacy Failure.; End of Study was defined as the last day of evaluation and could have included bivariate assessments after 36 months.
Clinically Treated Acute Rejection	End of Study (36 months)	Clinically treated acute rejection is defined as patient incidence of any rejection (suspected or otherwise) for which treatment was provided. Data is reported as the percentage of patients with Clinically Treated Acute Rejection.; End of Study was defined as the last day of evaluation and could have included bivariate assessments after 36 months.
Time to First BCAR	End of Study (36 months)	Time to first BCAR is defined as the number of days from skin closure to the first episode of BCAR.; End of Study was defined as the last day of evaluation and could have included bivariate assessments after 36 months.
Graft Survival at 12 Months	12 months	Graft survival is defined as no graft loss (re-transplant, return to dialysis for more than 30 days or death) with 12 months of skin closure.; Kaplan Meier analysis was used to estimate percentage of patients with event. Patients with no event by the time of the scheduled visit or whose first event was after premature discontinuation of randomized study drug or tacrolimus were censored on the scheduled day of assessment, on the day of premature treatment discontinuation or last evaluation day, whichever came first.
Overall Graft Survival	End of Study (36 months)	Overall graft survival is defined as not having graft loss (re-transplant, return to dialysis for more than 30 consecutive days, or death) at any time following skin closure. Data is reported as the percentage of patients with Overall Graft Survival.; End of Study was defined as the last day of evaluation and could have included bivariate assessments after 36 months.
Patient Survival at 12 Months	12 months	Patient survival is defined as not dead within 12 months after skin closure.; Kaplan Meier analysis was used to estimate percentage of patients with event. Patients with no event by the time of the scheduled visit or whose first event was after premature discontinuation of randomized study drug or tacrolimus were censored on the scheduled day of assessment, on the day of premature treatment discontinuation or last evaluation day, whichever came first.
Overall Patient Survival	End of Study (36 months)	Overall patient survival is defined as not dead at any time following skin closure. Data is reported as the percentage of patients with Overall Patient Survival.; End of Study was defined as the last day of evaluation and could have included bivariate assessments after 36 months.
Renal Function Abnormalities Based on Creatinine Clearance	1 month and End of Study (36 months)	Increases in creatinine clearance usually indicates an improvement.; Change in creatinine clearance from month 1 was calculated.; Change from 1 month is calculated by month 36 - month 1.
Renal Function Abnormalities Based on Serum Creatinine	1 month and End of Study (36 months)	Decrease in serum creatinine usually indicates an improvement.; Change in creatinine clearance from month 1 was calculated.; Change from 1 month is calculated by month 36 - month 1.