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

NCT ID: NCT00332839

Last Updated: 2014-08-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 93 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-30
• Study Completion Date: 2013-03-31

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.

Conditions

Renal Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Calcineurin Inhibitor (CNI) group

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.

Group Type: ACTIVE_COMPARATOR

Cyclosporin A (CsA)

Intervention Type: DRUG

The dose was based on the participants' blood level of C0h (80-150 ng/ml).

Tacrolimus

Intervention Type: DRUG

The dose was based on the participants' blood level of C0h (5-10 ng/ml).

Enteric Coated - Mycophenolate Sodium (EC-MPS)

Intervention Type: DRUG

The dose was ≥ 720 mg/day.

Corticosteroids

Intervention Type: DRUG

Corticosteroids were given according to local standard and/or the Investigators' discretion.

Certican group

Participants were switched in a step-wise fashion from the CNI based regimen to Everolimus (RAD001).

Group Type: EXPERIMENTAL

Everolimus

Intervention Type: DRUG

Participants, switching from the CsA based treatment, initially received everolimus 1.5 mg/day and then from day 7, 3 mg/day, and then from day 14, the dose was based on the participants' blood level (6-10 ng/ml). Participants, switching from the tacrolimus based treatment, initially received 3 mg/day and then from day 14, the dose was based on the participants' blood level (6-10 ng/ml).

Enteric Coated - Mycophenolate Sodium (EC-MPS)

Intervention Type: DRUG

The dose was ≥ 720 mg/day.

Corticosteroids

Intervention Type: DRUG

Corticosteroids were given according to local standard and/or the Investigators' discretion.

Interventions

Everolimus

Participants, switching from the CsA based treatment, initially received everolimus 1.5 mg/day and then from day 7, 3 mg/day, and then from day 14, the dose was based on the participants' blood level (6-10 ng/ml). Participants, switching from the tacrolimus based treatment, initially received 3 mg/day and then from day 14, the dose was based on the participants' blood level (6-10 ng/ml).

Intervention Type: DRUG

Cyclosporin A (CsA)

The dose was based on the participants' blood level of C0h (80-150 ng/ml).

Intervention Type: DRUG

Tacrolimus

The dose was based on the participants' blood level of C0h (5-10 ng/ml).

Intervention Type: DRUG

Enteric Coated - Mycophenolate Sodium (EC-MPS)

The dose was ≥ 720 mg/day.

Intervention Type: DRUG

Corticosteroids

Corticosteroids were given according to local standard and/or the Investigators' discretion.

Intervention Type: DRUG

Other Intervention Names

RAD001, Certican; Sandimmun Optoral; Prograf; Myfortic

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Novartis

Role: STUDY_DIRECTOR

Novartis

Locations

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Cologne, , Germany

Novartis Investigative Site

Erlangen, , Germany

Novartis Investigative Site

Essen, , Germany

Novartis Investigative Site

Hanover, , Germany

Novartis Investigative Site

Heidelberg, , Germany

Novartis Investigative Site

Heilbronn, , Germany

Novartis Investigative Site

Kaiserslautern, , Germany

Novartis Investigative Site

Kiel, , Germany

Novartis Investigative Site

Münster, , Germany

Countries

Germany

Other Identifiers

2005-001013-18

Identifier Type: -

Identifier Source: secondary_id

CRAD001ADE02

Identifier Type: -

Identifier Source: org_study_id