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

This study has been terminated.
(The trial was terminated early due to slow enrollment. It was determined that the planned sample size of 300 could not be achieved.)
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00332839
First received: May 31, 2006
Last updated: August 15, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Renal Transplantation
Drug: Everolimus
Drug: Cyclosporin A (CsA)
Drug: Tacrolimus
Drug: Enteric Coated - Mycophenolate Sodium (EC-MPS)
Drug: Corticosteroids
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Multi-center, Open-label, Prospective, Randomized, Parallel Group Study Investigating a CNI-free Regimen With Enteric-coated Mycophenolate Sodium and Everolimus in Comparison to Standard Therapy With Enteric-coated Mycophenolate Sodium and Ciclosporin Microemulsion in Stable Renal Transplant Patients

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Renal Function [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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:
  • Biopsy Proven Acute Rejection, Graft Loss, and Death [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline, 12 months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline, 12 months ] [ Designated as safety issue: Yes ]
    The analysis for this outcome measure was not perfomed because the analyses could not be powered for efficacy due to low recruitment.


Enrollment: 93
Study Start Date: November 2005
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
Drug: Cyclosporin A (CsA)
The dose was based on the participants' blood level of C0h (80-150 ng/ml).
Other Name: Sandimmun Optoral
Drug: Tacrolimus
The dose was based on the participants' blood level of C0h (5-10 ng/ml).
Other Name: Prograf
Drug: Enteric Coated - Mycophenolate Sodium (EC-MPS)
The dose was ≥ 720 mg/day.
Other Name: Myfortic
Drug: Corticosteroids
Corticosteroids were given according to local standard and/or the Investigators' discretion.
Experimental: Certican group
Participants were switched in a step-wise fashion from the CNI based regimen to Everolimus (RAD001).
Drug: 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).
Other Name: RAD001, Certican
Drug: Enteric Coated - Mycophenolate Sodium (EC-MPS)
The dose was ≥ 720 mg/day.
Other Name: Myfortic
Drug: Corticosteroids
Corticosteroids were given according to local standard and/or the Investigators' discretion.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

Other protocol-defined exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00332839

Locations
Germany
Novartis Investigative Site
Berlin, Germany, 13353
Novartis Investigative Site
Berlin, Germany, 10098
Novartis Investigative Site
Erlangen, Germany, 91054
Novartis Investigative Site
Essen, Germany, 45122
Novartis Investigative Site
Hannover, Germany, 30625
Novartis Investigative Site
Heidelberg, Germany, 69115
Novartis Investigative Site
Heilbronn, Germany, 74076
Novartis Investigative Site
Kaiserslautern, Germany, 67655
Novartis Investigative Site
Kiel, Germany, 24105
Novartis Investigative Site
Koeln, Germany, 51109
Novartis Investigative Site
Muenster, Germany, 48149
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Study Director: Novartis Novartis
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00332839     History of Changes
Other Study ID Numbers: CRAD001ADE02, 2005-001013-18
Study First Received: May 31, 2006
Results First Received: March 14, 2014
Last Updated: August 15, 2014
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Novartis:
enteric-coated mycophenolate sodium, everolimus, CNI-free regimen

Additional relevant MeSH terms:
Everolimus
Sirolimus
Tacrolimus
Cyclosporins
Cyclosporine
Mycophenolate mofetil
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on September 16, 2014