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

• Overall Patient Incidence of BCAR [ Time Frame: End of Study (36 months) ] [ Designated as safety issue: No ]

  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 [ Time Frame: End of Study (36 months) ] [ Designated as safety issue: No ]

  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 [ Time Frame: End of Study (36 months) ] [ Designated as safety issue: No ]

  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 [ Time Frame: End of Study (36 months) ] [ Designated as safety issue: No ]

  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 [ Time Frame: 12 months ] [ Designated as safety issue: No ]

  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 [ Time Frame: End of Study (36 months) ] [ Designated as safety issue: No ]

  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 [ Time Frame: 12 months ] [ Designated as safety issue: No ]

  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 [ Time Frame: End of Study (36 months) ] [ Designated as safety issue: No ]

  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 [ Time Frame: 1 month and End of Study (36 months) ] [ Designated as safety issue: No ]

  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 [ Time Frame: 1 month and End of Study (36 months) ] [ Designated as safety issue: No ]

  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.

• Time to first acute rejection episode
• One year patient and graft survival rates

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.

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.

• Drug: basiliximab
  IV
  Other Name: simulect
• Drug: rabbit anti-thymocyte globulin
  IV
  Other Name: Thymoglobulin
• Drug: tacrolimus
  oral
  Other Name: Prograf, FK506
• Drug: alemtuzumab
  Intravenous (IV)
  Other Name: campath
• Drug: mycophenolate mofetil
  oral
  Other Names:

  • MMF
  • CellCept
• Drug: steroids
  IV and/or oral

• Experimental: Alemtuzumab High-Risk Patients
  Alemtuzumab, tacrolimus, mycophenolate mofetil and steroids; High risk patients: Panel reactive antibody ≥ 20% or re-transplant or African American
  Interventions:

  • Drug: tacrolimus
  • Drug: alemtuzumab
  • Drug: mycophenolate mofetil
  • Drug: steroids
• Active Comparator: Conventional High-Risk Patients
  Rabbit anti-thymocyte globulin, tacrolimus, mycophenolate mofetil and steroids; High risk patients: Panel reactive antibody ≥ 20% or re-transplant or African American
  Interventions:

  • Drug: rabbit anti-thymocyte globulin
  • Drug: tacrolimus
  • Drug: mycophenolate mofetil
  • Drug: steroids
• Experimental: Alemtuzumab Low- Risk Patients
  Alemtuzumab, tacrolimus, mycophenolate mofetil and steroids; Low risk patients: Panel reactive antibody < 20% and first transplant and non-African American
  Interventions:

  • Drug: tacrolimus
  • Drug: alemtuzumab
  • Drug: mycophenolate mofetil
  • Drug: steroids
• Active Comparator: Conventional Low-Risk Patients
  Basiliximab, tacrolimus, mycophenolate mofetil and steroids; Low risk patients: Panel reactive antibody < 20% and first transplant and non-African American
  Interventions:

  • Drug: basiliximab
  • Drug: tacrolimus
  • Drug: mycophenolate mofetil
  • Drug: steroids

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