Efficacy, Safety and Evolution of Cardiovascular Parameters in Renal Transplant Recipients
Condition: Kidney Transplantation
Intervention: Everolimus; Prograf or Neoral
Intervention description: Early CNI to everolimus conversion; Active CNI-based control (Prograf or Neoral)
Intervention MeSH terms: Cyclosporine; Everolimus; Tacrolimus; Cyclosporins
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 828.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: de novo renal allograft recipients; renal allograft function; CNI-free regimen

Summary:

      The purpose of this study was to determine whether an early Calcineurin Inhibitor (CNI) to
      everolimus conversion at 10-14 weeks post transplantation improves renal allograft function
      without compromising efficacy compared to standard CNI treatment in de novo renal allograft
      recipients. In addition, the study was designed to evaluate the impact of a CNI-free regimen
      on evolution of cardiovascular parameters in de novo renal allograft recipients
    

Eligibility criteria:

        Inclusion Criteria at Baseline:

          -  Male or female renal allograft recipients at least 18 years old.

          -  Written informed consent.

          -  Patient receiving a primary or secondary kidney transplant from a cadaveric or living
             unrelated-/related donor.

          -  Cold ischemia time (CIT) < 24 hours.

          -  Negative pregnancy test for female patients.

        Inclusion Criteria at Randomization:

          -  Patients on CNI (TAC or CsA) + Myfortic + steroids.

          -  Serum creatinine < 2.8 mg/dL (250 µmol/L) and an actual eGFR (MDRD4) ≥ 25 mL/min/1.73m
             exp2 (without renal replacement therapy).

        Exclusion Criteria at Baseline:

        Patients fulfilling any of the following criteria are not eligible for inclusion in this
        study:

          -  Recipient of multiple organ transplants.

          -  Recipient of ABO incompatible allograft or a positive cross-match.

          -  Panel Reactive Antibodies (PRA) level ≥ 30 %.

          -  Positive test for human immunodeficiency virus (HIV).

          -  Patient receiving an allograft from a Hepatitis B surface Antigen (HBsAg) or a
             Hepatitis C Virus (HCV) positive donor.

          -  HBsAg and/or a HCV positive patient with evidence of elevated LFTs (ALT/AST levels ≥
             2.5 times ULN).

          -  Severe restrictive or obstructive pulmonary disorders.

          -  Patient with severe allergy requiring acute or chronic treatment or hypersensitivity
             to any of the study drugs or similar drugs.

          -  Severe hypercholesterolemia or hypertriglyceridemia.

          -  Low platelet count.

          -  Low white blood cell count.

          -  History of malignancy of any organ system

        Exclusion Criteria at Randomization:

          -  Graft loss.

          -  Patient on renal replacement therapy.

          -  Patient who experienced severe humoral and/or cellular rejection (BANFF ≥ IIb).

          -  Patient with ≥ 2 episodes of AR or an AR episode that needed antibody treatment.

          -  Patient with ongoing or currently treated AR (2 weeks prior to randomization).

          -  Proteinuria > 1 g/day.

          -  Patients with recurrence of Focal Segmental Glomerulosclerosis (FSGS).

          -  Low platelet count; Low white blood cell count; Low absolute neutrophil count; Low
             hemoglobin.

          -  Severe liver disease.

          -  Systemic infection requiring continued therapy that would interfere with the
             objectives of the study.

          -  Severe hypercholesterolemia or hypertriglyceridemia.

          -  Patients with ongoing wound healing problems, clinically significant infection
             requiring continued therapy.

          -  Presence of intractable immunosuppressant complications or side effects.

          -  Patients on anticoagulants that prevents renal allograft biopsy.

          -  Use of prohibited medication.

          -  Use of immunosuppressive agents not utilized in the protocol.

          -  Pregnant or nursing (lactating) women.

          -  Women of child-bearing potential not using a highly effective method of birth control.