Comparison of CNI-based Regimen Versus CNI-free Regimen in Kidney Transplant Recipients.

Phase 4

Terminated

Conditions: Renal Transplantation

Interventions: Drug: Cyclosporin A (CsA)
Drug: Everolimus
Drug: Tacrolimus
Drug: Corticosteroids
Drug: Enteric Coated - Mycophenolate Sodium (EC-MPS)

Registration Number: NCT00332839

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: Calcineurin inhibitors (CNI), a potent immunosuppressive drug used in kidney transplant recipients to prevent graft rejection, may cause renal impairment. The aim of this study is to assess whether a CNI-free regimen with enteric-coated mycophenolate sodium and everolimus is as safe and well tolerated as a standard regimen consisting of enteric-coated mycophenolate sodium and cyclosporine microemulsion without a compromise in therapeutic efficacy while resulting in an improved renal function.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 93

Inclusion Criteria

Males or females, aged > 18 years, Maintenance renal transplant recipients at least 6 months post-transplantation, Patients with a serum creatinine < 2,5 mg/dL stable for at least three month (according to the investigator), Females capable of becoming pregnant had to have a negative serum pregnancy test within seven days prior to or at baseline, and were required to practice an approved method of birth control for the duration of the study and for a period of six weeks following discontinuation of study medication, even where there had been a history of infertility, Patients receiving Myfortic® (Myfortic dose . 720 mg/d) and Sandimmun® Optoral with or without corticosteroids as part of their immunosuppressive regimen for at least 1 month before baseline;

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, Patient with proteinuria > 1000 mg/day at baseline, Hypersensitivity to Certican®, Sandimmun® Optoral, Prograf®, mycophenolic acid, or other components of the formulation, Patients who had received an investigational drug within four weeks prior to baseline, Severe rejection (≥ Banff II acute rejection), recurrent acute rejection, or steroid resistant rejection within six months of enrollment, Thrombocytopenia (platelets < 100,000/mm³), with an absolute neutrophil count of < 1,500/mm³ or leukopenia (leukocytes < 4,000/mm³), or hemoglobin < 8 g/dL, Abnormal physical or laboratory findings of clinical significance within two weeks of study inclusion which at the investigator's discretion would interfere with the objectives of the study, Symptoms of significant somatic or mental illness. Inability to cooperate or communicate with the investigator, or patients who were unlikely to comply with the study requirements, or who were unable to give informed consent, History of malignancy during the last five years, except squamous or basal cell carcinoma of the skin, Patients who were HIV positive, or hepatitis C, or hepatitis B surface antigen positiveEvidence of severe liver disease (including abnormal liver enzyme profile, i.e. aspartate transaminase (AST), alanine aminotransferase (ALT) or total bilirubin > 3 times upper limit of normal (ULN), Females of childbearing potential who were planning to become pregnant, who were pregnant or lactating and/or who were unwilling to use effective means of contraception, 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

Other protocol-defined exclusion criteria may apply.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Calcineurin Inhibitor (CNI) group	Cyclosporin A (CsA)	Participants received Cyclosporine A (CsA) plus Enteric Coated Mycophenolate Sodium (EC-MPS) plus corticosteroids, or Tacrolimus A (CsA) plus Enteric Coated Mycophenolate Sodium (EC-MPS) plus corticosteroids.
Certican group	Corticosteroids	Participants were switched in a step-wise fashion from the CNI based regimen to Everolimus (RAD001).
Calcineurin Inhibitor (CNI) group	Enteric Coated - Mycophenolate Sodium (EC-MPS)	Participants received Cyclosporine A (CsA) plus Enteric Coated Mycophenolate Sodium (EC-MPS) plus corticosteroids, or Tacrolimus A (CsA) plus Enteric Coated Mycophenolate Sodium (EC-MPS) plus corticosteroids.
Certican group	Enteric Coated - Mycophenolate Sodium (EC-MPS)	Participants were switched in a step-wise fashion from the CNI based regimen to Everolimus (RAD001).
Calcineurin Inhibitor (CNI) group	Corticosteroids	Participants received Cyclosporine A (CsA) plus Enteric Coated Mycophenolate Sodium (EC-MPS) plus corticosteroids, or Tacrolimus A (CsA) plus Enteric Coated Mycophenolate Sodium (EC-MPS) plus corticosteroids.
Calcineurin Inhibitor (CNI) group	Tacrolimus	Participants received Cyclosporine A (CsA) plus Enteric Coated Mycophenolate Sodium (EC-MPS) plus corticosteroids, or Tacrolimus A (CsA) plus Enteric Coated Mycophenolate Sodium (EC-MPS) plus corticosteroids.
Certican group	Everolimus	Participants were switched in a step-wise fashion from the CNI based regimen to Everolimus (RAD001).

Primary Outcome Measures

Name	Time	Method
Renal Function	12 months	The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment.

Secondary Outcome Measures

Name	Time	Method
Biopsy Proven Acute Rejection, Graft Loss, and Death	12 months	The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment.
Occurrence of Treatment Failures	12 months	The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment.
Evolution of Renal Function	Baseline, 12 months	The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment.
Number of Participants Who Experienced Adverse Events and Death	12 months	Participants were monitored for adverse events, serious adverse events and deaths thorughout the prospective and follow-up phases of the study.
Changes in Cardiovascular Risk	Baseline, 12 months	The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment.
Changes in Proteinuria	Baseline, 12 months	The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment.