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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase 4, Randomized, Open-label, Comparative, Multicenter Study to Assess the Safety and Efficacy of Induction Agents, Alemtuzumab, Basiliximab or Rabbit Anti-thymocyte Globulin in Combination With Tacrolimus, MMF, and a Rapid Steroid Withdrawal in Renal Transplant Recipients

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Drug: basiliximab
* Drug: rabbit anti-thymocyte globulin
* Drug: tacrolimus
* Drug: alemtuzumab
* Drug: mycophenolate mofetil
* Drug: steroids


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alemtuzumab High-Risk Patients<br>Alemtuzumab, tacrolimus, mycophenolate mofetil and steroids; High risk patients: Panel reactive antibody ≥ 20% or re-transplant or African American | Drug: tacrolimus<br>* oral<br>* Other names: Prograf, FK506;Drug: alemtuzumab<br>* Intravenous (IV)<br>* Other names: campath;Drug: mycophenolate mofetil<br>* oral<br>* Other names: CellCept;Drug: steroids<br>* IV and/or oral<br>|
| Active Comparator: Conventional High-Risk Patients<br>Rabbit anti-thymocyte globulin, tacrolimus, mycophenolate mofetil and steroids; High risk patients: Panel reactive antibody ≥ 20% or re-transplant or African American | Drug: rabbit anti-thymocyte globulin<br>* IV<br>* Other names: Thymoglobulin;Drug: tacrolimus<br>* oral<br>* Other names: Prograf, FK506;Drug: mycophenolate mofetil<br>* oral<br>* Other names: CellCept;Drug: steroids<br>* IV and/or oral<br>|
| Experimental: Alemtuzumab Low- Risk Patients<br>Alemtuzumab, tacrolimus, mycophenolate mofetil and steroids; Low risk patients: Panel reactive antibody < 20% and first transplant and non-African American | Drug: tacrolimus<br>* oral<br>* Other names: Prograf, FK506;Drug: alemtuzumab<br>* Intravenous (IV)<br>* Other names: campath;Drug: mycophenolate mofetil<br>* oral<br>* Other names: CellCept;Drug: steroids<br>* IV and/or oral<br>|
| Active Comparator: Conventional Low-Risk Patients<br>Basiliximab, tacrolimus, mycophenolate mofetil and steroids; Low risk patients: Panel reactive antibody < 20% and first transplant and non-African American | Drug: basiliximab<br>* IV<br>* Other names: simulect;Drug: tacrolimus<br>* oral<br>* Other names: Prograf, FK506;Drug: mycophenolate mofetil<br>* oral<br>* Other names: CellCept;Drug: steroids<br>* IV and/or oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Incidence of Biopsy-confirmed Acute Rejection (BCAR) at 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. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Patient Incidence of BCAR | 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. | End of Study (36 months) | 
| Efficacy Failure | 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. | End of Study (36 months) | 
| Clinically Treated Acute Rejection | 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. | End of Study (36 months) | 
| Time to First BCAR | 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. | End of Study (36 months) | 
| Graft Survival at 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. | 12 months | 
| Overall Graft Survival | 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. | End of Study (36 months) | 
| Patient Survival at 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. | 12 months | 
| Overall Patient Survival | 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. | End of Study (36 months) | 
| Renal Function Abnormalities Based on Creatinine Clearance | 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. | 1 month and End of Study (36 months) | 
| Renal Function Abnormalities Based on Serum Creatinine | 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. | 1 month and End of Study (36 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment Effectiveness, Treatment Efficacy, Anti-rejection therapy, Immunosuppression, Therapy, antirejection, Renal Transplantation, Transplantation, Kidney, Transplantation, Renal, Grafting, Kidney