Improved Induction and Maintenance Immunosuppression in Kidney Transplantation
Condition: End-stage Renal Disease
MeSH terms: Kidney Failure, Chronic
Intervention: rabbit anti-thymocyte globulin - single dose; mycophenolate mofetil; rabbit anti-thymocyte globulin - 4 doses; sirolimus; tacrolimus
Intervention description: A single 6 mg/kg dose of rATG administered intravenously over 24 hours, beginning before kidney transplantation. Administration of the drug is begun as early as practical, usually after general anesthesia has been established but before surgery has started. The rATG is therefore administered for about two hours before blood flow is restored to the kidney undergoing transplantation.; Patients are switched approximately 6 months after kidney transplantation from maintenance immunosuppression with tacrolimus and sirolimus to maintenance with mycophenolate mofetil and sirolimus. The drug is administered orally, taken daily, with dose adjusted in proportion to measured blood levels, and is required indefinitely to prevent rejection of the transplanted kidney.; 6 mg/kg rabbit anti-thymocyte globulin delivered in 4 doses of 1.5 mg/kg each, the first administered at the time of kidney transplantation. Subsequent doses are administered on days 2, 4, and 6.; Oral maintenance immunosuppressant administered daily, dose adjusted according to measured serum trough levels, continued indefinitely to prevent kidney rejection; Oral maintenance immunosuppressant, taken daily, dose adjusted to maintain target blood trough levels, required indefinitely to prevent kidney rejection.
Intervention MeSH terms: Mycophenolic Acid; Sirolimus; Tacrolimus; Thymoglobulin; Antilymphocyte Serum
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Enrollment: 180.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Induction; rATG; Calcineurin-inhibitor withdrawal

Summary:

      This 2 x 2 sequential factorial study evaluates two potential improvements to the standard
      immunosuppression regimen used at the investigators' institution to prevent rejection of
      transplanted kidneys. These two potential improvements are each applied in sequence to half
      of the study patients, creating 4 study arms; the other half receive the standard treatment.
      The two potential improvements are:

        1. Administering the immunosuppression induction agent rATG ("rabbit anti-thymocyte
           globulin") in a single dose at the time of transplantation, instead of in the usual
           series of 4 smaller doses over 6 days.

        2. After 6 months, modifying the maintenance immunosuppression used to prevent rejection by
           replacing the drug tacrolimus with mycophenolate mofetil (MMF).

      The two interventions, spaced sequentially six months apart, enable independent analysis of
      the two treatments so long as it can be shown that there is no synergistic interaction
      between them.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Primary renal transplant recipient for end-stage renal disease

        Exclusion Criteria:

          -  Recipient age < 18 years or > 65 years

          -  Previous history of CMV disease

          -  Hepatitis B and C recipients

          -  Primary disease states that require steroids for immunosuppression

          -  Re-transplant with immunological cause of renal or pancreas loss

          -  Non heart beating donors

          -  Recipient of pediatric en bloc kidneys

          -  Recipient with a Panel Reactive Antibody (PRA) score >75%

          -  Patients who have received 3 or more prior transplants, excluding pancreas

          -  Patients who are past recipients of other solid organ transplants

          -  Previous history of BK virus

          -  Previous treatment with Thymoglobulin

          -  Allergy to rabbits

          -  Simultaneous Kidney/Pancreas transplantation