Efficacy and Safety of Everolimus+EC-MPS After Early CNI Elimination vs EC-MPS +Tacrolimus in Renal Transplant Recipients
Condition: Chronic Renal Failure
MeSH terms: Kidney Failure, Chronic
Intervention: Everolimus; Tacrolimus (FK506); Basiliximab; Enteric Coated Mycophenolate Sodium (EC-MPS); Corticosteroids
Intervention description: One tablet containing 0.25, 0.5mg or 0.75 mg. Initially 2 mg/day. Afterwards based on blood level (target 6-10 ng/mL); Capsules 0.5 mg, 1 mg. Dosing according to blood level.; One vial containing 20 mg lyophilisate. 2 x 20 mg [day 0 (2 hrs prior to Tx) and day 4 post Tx] to be applied as 10 sec. bolus injection, i.v.; One tablet containing 180 mg or 360 mg. 1440 mg/day (2x720 mg). If tolerated, dose reduction due to side effectis were possible (min. dose at BL@: 720 mg/day); Used according to Israeli standards. A minimum dose of 5mg [prednisone, or equivalent, was used throughout the study period.
Intervention MeSH terms: Mycophenolic Acid; Everolimus; Tacrolimus; Basiliximab
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      The primary objective of this trial is to show non-inferiority of a CNI-free regimen with
      respect to the renal function at Month 9 post Tx assessed by glomerular filtration rate -
      Nankivell method - as compared to the standard CNI-based regimen in de novo renal transplant
      patients.
    

Eligibility criteria:

        Inclusion criteria:

          -  Recipients of de novo cadaveric, living unrelated or living related kidney transplants

          -  Females capable of becoming pregnant must have a negative serum pregnancy test within
             7 days prior to or at screening, and are required to practice an approved method of
             birth control for the duration of the study and for a period of 6 weeks following
             discontinuation of study medication, even where there has been a history of
             infertility.

          -  Patients who are willing and able to participate in the study and from whom written
             informed consent has been obtained.

        Exclusion criteria:

          -  More than one previous renal transplantation

          -  Multi-organ recipients (e.g., kidney and pancreas) or previous transplant with any
             other organ, different from kidney

          -  Donor age: < 5 years or > 65 years

          -  Graft loss due to immunological reasons in the first year after transplantation (in
             case of secondary transplantation)

          -  Patients who had received an investigational drug within 4 weeks of the baseline
             period

          -  Patients who are recipients of A-B-O incompatible transplants or T cell cross-match
             positive transplants

          -  Patients with already existing antibodies against the HLA-type of the receiving
             transplant

          -  Patients with any known hypersensitivity to Simulect®, Certican®, mycophenolic acid,
             Prograf®, other drugs similar to Certican® (e.g., macrolides), or other components of
             the formulations.

          -  Patients who have received an investigational immunosuppressive drug within four weeks
             prior to study entry (Baseline visit 1)

          -  Patients with thrombocytopenia (platelets < 75,000/mm³), or an absolute neutrophil
             count of < 1,500/mm³ or leucopenia (leucocytes < 2,500/mm³), or hemoglobin < 6 g/dL

          -  Patients with preexisting lung disease (alveolitis, fibrosis) Patients with symptoms
             of significant somatic or mental illness. Inability to cooperate or communicate with
             the investigator, who are unlikely to comply with the study requirements, or who are
             unable to give informed consent

          -  Patients with a history of malignancy during the last five years, except squamous or
             basal cell carcinoma of the skin

          -  Patients who are HIV positive or Hepatitis B surface antigen positive or Hepatitis C
             virus positive. Recipients of organs from donors who test positive for Hepatitis B
             surface antigen or Hepatitis C are excluded.

          -  Evidence of severe liver disease (incl. abnormal liver enzyme profile, i.e. AST, ALT
             or total bilirubin > 3 times UNL)

          -  Females of childbearing potential who are planning to become pregnant, who are
             pregnant or lactating, and/or who are unwilling to use effective means of
             contraception (see also section 8.2)

          -  Presence of a clinically significant infection requiring continued therapy, severe
             diarrhea, active peptic ulcer disease, or uncontrolled diabetes mellitus that in the
             opinion of the investigator would interfere with the appropriate conduct of the study

          -  Evidence of drug or alcohol abuse

          -  Patients receiving drugs known to interact with Tacrolimus and/or everolimus according
             to the list provided in Appendix 3 to this protocol.

          -  Other protocol-defined inclusion/exclusion criteria may apply