Everolimus and Low Dose CNI Compared With MMF and Full CNI Dose in Heart Transplanted Patients: One Year Follow up (CRAD001AILO2)

This study has been completed.
Sponsor:
Information provided by:
Rabin Medical Center
ClinicalTrials.gov Identifier:
NCT00596557
First received: January 8, 2008
Last updated: July 28, 2011
Last verified: July 2011
  Purpose

The different mechanisms of action of Everolimus and cyclosporine suppress immune function in synergistic manner. Thus it is postulated that the use of Everolimus in combination with cyclosporine permits a significant cyclosporine dose reduction without loss of immunosuppressive activity in the clinical setting.

The aim of the present study is to evaluate the evolution of renal function after initiation of Everolimus and minimalisation of CNI dose.


Condition Intervention Phase
Chronic Rejection of Cardiac Transplant
Drug: everolimus
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Phase IV: Effect of Everolimus and CNI Minimalization on Renal Function.

Resource links provided by NLM:


Further study details as provided by Rabin Medical Center:

Primary Outcome Measures:
  • Evolution of renal function after initiation of Everolimus and minimalisation of CNI dose. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The occurrence of major adverse cardiovascular events [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Enrollment: 20
Study Start Date: February 2008
Study Completion Date: July 2011
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus, Immunosupression
everolimus and reduced dose CNI: reduced dose CNI (cyclosporine level of 50-100)with everolimus levels of 3-8.
Drug: everolimus
reduced dose CNI (cyclosporine level of 50-100)with everolimus levels of 3-8.
Other Name: certican

Detailed Description:

Everolimus is a new proliferation signal inhibitor with immunosuppressive and antiproliferative activity.

The mechanism of action of Everolimus is distinct from that of calcineurin inhibitors.

Cardiac allograft vasculopathy is the major cause of late death in cardiac transplant patients.

The different mechanisms of action of Everolimus and cyclosporine suppress immune function in synergistic manner. Thus it is postulated that the use of Everolimus in combination with cyclosporine permits a significant cyclosporine dose reduction without loss of immunosuppressive activity in the clinical setting.

The aim of the present study is to evaluate the evolution of renal function after initiation of Everolimus and minimalisation of CNI dose.

  Eligibility

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

Inclusion Criteria:

  • Age ≥ 18 year
  • Signed informed consent
  • 6 months to 15 year after heart transplantation
  • Stable heart allograft function without rejection for at least 12 months
  • Same immunusuppressive drugs for at least 3 months
  • CNI based immunusuppression, with Cyclosporin levels C0 100-200 ng/ml FK levels of 5-10 ng/ml for preserved CNI levels.
  • Poor renal function: creatinine > 1.5 mg%.

Exclusion Criteria:

  • Suspected non-compliance
  • Intolerance to Everolimus
  • Life expectancy < 1year
  • Proteinuria > 1.5 g/24u/1.73m2
  • Previous sirolimus treatment
  • Patients who received any other investigational drug
  • Patients with platelet count <50,000/mm³ before baseline.
  • Presence of severe hypercholesterolemia (≥350 mg/dL; ≥9 mmol/L) or hypertriglyceridemia (≥750 mg/dL; ≥8.5 mmol/L)
  • Patients with an absolute neutrophil count of ≤ 1,500/mm3 or white blood cell count of ≤ 4000/mm³ at baseline
  • Patients with a known hypersensitivity to similar drugs and to the components of the formulations
  • Patients being treated with terfenadine, astemizole, or cisapride.
  • Patients who are treated with drugs strong inducers or inhibitors of cytochrome P450 3A4.
  • Patients with any past (within the past 5 years) or present malignancy (other than excised basal cell carcinoma)
  • Patients with clinically significant systemic infection.
  • Existence of any surgical or medical condition, which in the opinion of the investigator, might significantly alter the absorption, distribution, metabolism and excretion of study medication, and/or the presence of severe diarrhea or active peptic ulcer.
  • Females of childbearing potential who are planning to become pregnant, who are pregnant and/or lactating, who are unwilling to use effective means of contraception.
  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: NCT00596557

Locations
Israel
Cardiology Department, Rabin Medical Center
Petah Tikva, Israel, 49100
Sponsors and Collaborators
Rabin Medical Center
Investigators
Principal Investigator: Tuvia Ben Gal, MD Rabin Medical Center
  More Information

No publications provided

Responsible Party: Tuvia Ben Gal MD, Director of the heart failure unit, Cardiology department, Rabin Medical Center
ClinicalTrials.gov Identifier: NCT00596557     History of Changes
Other Study ID Numbers: 004765
Study First Received: January 8, 2008
Last Updated: July 28, 2011
Health Authority: Israel: Ethics Commission

Keywords provided by Rabin Medical Center:
Renal function, heart transplant, everolimus

Additional relevant MeSH terms:
Everolimus
Sirolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents

ClinicalTrials.gov processed this record on September 11, 2014