Randomized Conversion of Calcineurin-Inhibitors in Renal Allograft Recipients
Condition: Renal Transplant Rejection
Intervention: Sirolimus; Demographic Data, Medical History, and Donor Data; Blood Draws for Control Group; Blood Draws for Experimental Group; Donor Blood Draws; Donor Information; Kidney Biopsy
Intervention description: Sirolimus will initially be given at a dose of 2-4 mg orally (PO) daily. The dose will be modified to achieve 24 hours trough concentrations of 6-10 ng/ml by high-performance liquid chromatography (HPLC) assay. This medication will be given in an open label fashion. The first dose of sirolimus will be given at the time of randomization to those patients assigned to have tacrolimus switched to sirolimus.; Age at transplant, sex, race, cause of end-stage renal disease, medical history, donor age, cadaveric vs. living kidney transplant, histocompatibility/cross match data, viral serology, history of acute rejection and delayed graft function, use of induction therapy and immunosuppressants, use of Angiotensin Converting Enzyme Inhibitor (ACEI) and/or Angiotensin Receptor Blockers (ARB) level of renal allograft function-estimated GFR (e-GFR(12) using Modification of Diet in Renal Disease (MDRD) formula, proteinuria.; Subjects maintaining standard of care drug treatment of TAC and MMF will have monthly labs in addition to the baseline pre-randomization labs, at 6, 12, and 24 Months post-randomization. Peripheral blood leukocytes will be obtained.; This group will have monthly labs taken but will also have weekly labs during the period of conversion to monitor renal function and bone marrow function. In addition to the baseline pre-randomization labs, and labs collected at 6, 12, and 24 Months post-randomization, peripheral blood leukocytes will be obtained.; Peripheral blood leukocytes from living donors obtained at the time of randomization. These donor leukocytes will be used as stimulator cells to study the functional activity of the recipient's lymphocytes function.; Donor age, cadaveric vs. living donor, and histocompatibility and cross match to recipient; Kidney biopsy at 24 Months to compare to the standard of care biopsy taken at 12 Months. This information will help evaluate renal allograft pathology and renal allograft tissue gene expression profiles of the two groups. Renal allograft biopsies will be stored in RNA later (preservative) to further extend knowledge on the effect of calcineurin-inhibitors (CI) free immunosuppression on gene expression profiles.
Intervention MeSH terms: Sirolimus
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 275.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Sirolimus; Rapamune; Immunosuppression; Renal allograft function; Lymphocytes function

Summary:

      This study is being done to investigate the impact of changing immunosuppressive medications
      from tacrolimus (Prograf®) to sirolimus (Rapamune®) between 6 and 24 months post transplant.
      The primary purpose of this research study is to evaluate whether the use of mycophenolate
      mofetil(MMF)/Cellcept® and tacrolimus(TAC)/Prograf® (Group 1) or mycophenolate
      mofetil(MMF)/Cellcept® and sirolimus/Rapamune® (Group 2) impacts the incidence of acute
      cellular rejection in post kidney transplant patients. This study will examine whether
      switching from tacrolimus to sirolimus will better preserve long-term kidney function.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subjects should be adults ≥ 18- ≤ 70 years of age

          2. Subjects can be either gender or of any ethnic background

          3. Subjects should be single organ recipients (kidney only)

          4. Subjects must be able to understand the protocol and provide informed consent.

        Exclusion Criteria:

          1. Subjects with end-stage renal disease (ESRD) secondary to primary focal segmental
             glomerulonephritis (FSGS).

          2. Inability to comply with study procedures

          3. Inability to sign the informed consent

          4. Subjects with a significant or active infection

          5. Subjects who are pregnant or nursing females

          6. Subjects with a history of severe hyperlipidemia not controlled with statins, patients
             with at total cholesterol of > 400 mg/dl

          7. Subjects with a platelet count <100,000mm3 white blood cell (WBC)< 2,000mm3

          8. Subjects with severe proteinuria at the time of randomization (>2gm/day)

          9. Subjects with more then 2 episodes of acute cellular rejection post transplantation
             will be excluded from this study

         10. An estimated GFR<40 cc/min

         11. A history of malignancy during the post-transplant period (other than treated basal
             cell cancer and/or squamous cell cancer)

         12. Subjects, who, due to the existence of a surgical, medical or psychiatric condition,
             other than the current transplant, which in the opinion of the investigator, precludes
             enrollment into this trial

         13. A history of albumin-creatinine ratio (ACR) during the most recent previous 3 months
             prior to randomization