Advancing Renal TRANSplant eFficacy and Safety Outcomes With an eveRolimus-based regiMen (TRANSFORM)
Condition: End Stage Renal Disease (ESRD); Chronic Kidney Disease (CKD); Hemodialysis; Renal Replacement Therapy; Renal Transplantation
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic
Intervention: Induction therapy; Corticosteroids; EVR+rCNI; MPA+sCNI
Intervention description: All subjects received induction therapy with basiliximab or rabbit anti-thymocyte globulin, in the peritransplant period.; All subjects received maintenance therapy with corticosteroids throughout the 24 month study period. A minimum dose of 5 mg prednisone, or equivalent, per day was maintained.; Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus); Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
Intervention MeSH terms: Cyclosporine; Prednisone; Methylprednisolone; Tacrolimus; Thymoglobulin; Cyclosporins; Basiliximab
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Open-label study
Masking: None (Open Label)
Enrollment: 2037.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: kidney failure; dialysis; renal failure; transplantation

Summary:

      This is a 2-year, randomized, multicenter, open-label, 2-arm study evaluating the graft
      function of everolimus and reduced CNI versus MPA and standard CNI in adult de novo renal
      transplant recipients.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Written informed consent obtained.

          2. Subject randomized within 24 hr of completion of transplant surgery.

          3. Recipient of a kidney with a cold ischemia time < 30 hours.

          4. Recipient of a primary (or secondary, if first graft is not lost due to immunological
             reasons) renal transplant from a deceased heart beating, living unrelated, living
             related non-human leukocyte antigen identical or an expanded criteria donor.

        Exclusion Criteria:

          1. Subject unable to tolerate oral medication at time of randomization.

          2. Use of other investigational drugs at the time of enrollment.

          3. History of hypersensitivity to any of the study drugs or to drugs of similar chemical
             classes.

          4. Multi-organ transplant recipient.

          5. Recipient of ABO incompatible allograft or complement-dependent lymphocytotoxic (CDC)
             crossmatch positive transplant.

          6. Subject at high immunological risk for rejection as determined by local practice for
             assessment of anti-donor reactivity e.g. high PRA, presence of pre-existing DSA.

          7. Subject who is HIV-positive.

          8. HBsAg and/or a HCV positive subject with evidence of elevated LFTs (ALT/AST levels ≥
             2.5 times ULN). Viral serology results obtained within 6 months prior to randomization
             are acceptable.

          9. Recipient of a kidney from a donor who tests positive for human immunodeficiency virus
             (HIV), hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (HCV).

         10. Subject with a BMI greater than 35.

         11. Subject with severe systemic infections, current or within the two weeks prior to
             randomization.

         12. Subject requiring systemic anticoagulation.

         13. History of malignancy of any organ system.

         14. Subject with severe restrictive or obstructive pulmonary disorders.

         15. Subject with severe hypercholesterolemia or hypertriglyceridemia that cannot be
             controlled.

         16. Subject with white blood cell (WBC) count ≤ 2,000 /mm3 or with platelet count ≤ 50,000
             /mm3.

         17. Pregnant or nursing (lactating) women.

         18. Women of child-bearing potential, defined as all women physiologically capable of
             becoming pregnant, unless they are using effective methods of contraception during
             dosing of study treatment.