Study Comparing Effect On Carotid Atherosclerosis Following Conversion From Tacrolimus To Sirolimus Post-Transplant In Kidney Transplant Patients

A decision to terminate the study was taken in November 2011 and a communication to that effect sent to all participating sites on November 18. All sites were asked to have patients returned to the sites and have all end of study procedures performed by Dec 31, 2011.

The decision to terminate this study was made following the conduct of an interim analysis which demonstrated that the study did not reach its primary endpoint. The termination of this study was not driven by any safety concerns and had no impact on subject safety and well-being.

• Atherosclerosis
• Kidney Failure

• Drug: tacrolimus
  The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol TAC should be initiated within 24 hours before or after transplantation or within 14 days of transplantation as per local standard of care and tapered to a target trough level of 3-10 ng/mL by the Pre-Conversion visit at month 3-4 post-transplantation. The target trough level of TAC will be maintained at 3-10 ng/mL through to the end of the study.
  Other Name: CNI
• Drug: mycophenolate mofetil
  The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol MMF or MPS should be initiated within 24 hours before or after transplantation or within 14 days of transplantation per local standard of care and tapered to a minimum oral dose of MMF ? 500 mg/day or MPS ? 360 mg/day by the Pre-Conversion visit at month 3-4 post-transplantation. At the discretion of the investigator, MMF may be changed to MPS, or MPS may be changed to MMF. MMF is to be continued at ? 500 mg/day dose or MPS is to be continued at ? 360 mg/day dose through to the end of study.
  Other Name: MMF, MPS
• Drug: prednisone
  The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol CCS should be initiated within 24 hours before or after transplantation or within 14 days of transplantation per local standard of care and tapered to a minimum of 5 mg/day of prednisone orally or the alternate day equivalent by the Pre-Conversion visit at month 3-4 post-transplant. Continue administration of prednisone as per local standard of care to a minimum dose of 2.5 mg/day or alternate day equivalent dose to the end of the study. Withdrawal of CCS is prohibited.
  Other Name: CCS
• Drug: sirolimus

  The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol.

  On study Day 1 Conversion, the daily dose of TAC will not be taken, and SRL is initiated as a single 5-10 mg loading dose, followed by 3 mg/day on subsequent days, adjusted to maintain a SRL target trough level of 8-15 ng/mL through to month 24 post-transplant, then 5-12 ng/mL to the end of month 36 post-transplant.

• Drug: tacrolimus
  The daily dosage and formulation for each study treatment will be chosen by the investigator as medically appropriate for each individual subject, in order to achieve the target levels specified in the protocol TAC should be initiated within 24 hours before or after transplantation or within 14 days of transplantation as per local standard of care and tapered to a target trough level of 3-10 ng/mL by the Pre-Conversion visit at month 3-4 post-transplantation. Reintroduction of TAC or introduction of CsA is not permitted in the SRL Therapy group.
  Other Name: CNI

• Active Comparator: 1
  Tacrolimus + MMF + Steroids
  Interventions:

  • Drug: tacrolimus
  • Drug: mycophenolate mofetil
  • Drug: prednisone
• Experimental: 2
  Tacrolimus + MMF + Steroids with conversion from Tacrolimus to Sirolimus at 3-4 months post-transplant
  Interventions:

  • Drug: sirolimus
  • Drug: tacrolimus
  • Drug: mycophenolate mofetil
  • Drug: prednisone

Inclusion Criteria:

At least one of the following characteristics:

• History of dialysis for at least 3 years.
• History of diabetes for at least 5 years.
• Hypertension or ischemic nephropathy as a cause of the end stage renal disease or loss of the first transplant.
• History of coronary artery disease, stroke, myocardial infarction, or amputation for vascular disease.

Exclusion Criteria:

• History of malignancy within the last 5 years (except adequately treated skin cancer).
• Recipients of non-renal organ transplant.
• Active gastrointestinal disease that may interfere with drug absorption.
• Active HIV, hepatitis B or C infection.
• Women who are pregnant or breastfeeding.