This trial is active, not recruiting.

Conditions cardiac transplantation, chronic renal insufficiency
Treatment everolimus
Phase phase 4
Targets mTOR, FKBP-12
Sponsor Hospices Civils de Lyon
Start date July 2008
End date March 2014
Trial size 206 participants
Trial identifier NCT00716573, 2007.495


After transplantation, renal impairment, incidence and progression of atherosclerosis lead to modification of immunosuppressive regimens, as switch, reduction or discontinuation of CNI and/or introduction of everolimus. The risk or benefits of these strategies were not clearly evaluated by specific clinical trials.

This study is specifically designed for evaluating the impact of everolimus introduction, with calcineurin dose reduction, at less one year after cardiac transplantation, on renal and clinical outcomes, specially on :

- Renal function improvement

- Vasculopathy and major cardiac event reduction

- Maintenance of immunosuppressive efficacy

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Introduction of everolimus associated with CNI (ciclosporin or tacrolimus) reduction (50%) to the current immunosuppression schedule
everolimus Certican
0,75 mg bid, 24 months
(No Intervention)
Maintain of their current immunosuppressive therapy

Primary Outcomes

Evaluation of the renal function, at 12 months after everolimus introduction and doses of anticalcineurins decrease.
time frame: 12 months

Secondary Outcomes

Evaluation of the benefit of everolimus introduction on renal function at 24 months
time frame: 24 months
Evaluation of the benefit of everolimus introduction on incidence of Major Adverse Cardiac Events (MACEs)
time frame: 24 months
Evaluation of the benefit of everolimus introduction on incidence of cardiovascular risk factor (Arterial Tension, diabetes, dyslipidemia, proteinuria)
time frame: 24 months
Evaluation of the benefit of everolimus introduction on incidence of treatment withdrawals
time frame: 24 months
Evaluation of the benefit of everolimus introduction on incidence of treated acute rejection
time frame: 24 months
Evaluation of the benefit of everolimus introduction on safety
time frame: 24 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Male or female cardiac recipients over 18 years old - First or second heart transplant, more than one year following surgery - Patients with renal failure assessed by cGFR 30 to 60 ml/min/1,73m² calculated by MDRD4 formula - Patients volunteer to participate in the study, with a written informed consent signed - Affiliation to a national health insurance program Exclusion Criteria: - Current CNI-free immunosuppressive regimen - Patients currently or previously treated with a mTOR inhibitor any time prior randomization - Patients who are recipients for a multiple solid organ transplant - Treated acute rejection episode within three months prior randomization - Congestive heart failure (NYHA class III or IV) and/or VEF < 30 % and/or patient waiting for a re-transplantation - Scheduled surgical intervention - Platelet count < 50 G/l - Severe hepatic insufficiency (SGPT and/or SGOT > 3N) - Major lipidic profile abnormalities (total cholesterol > 3g/l and/or TG > 5g/l) - Proteinuria/creatinuria > 0,08 g/mmol - Severe renal failure attested by cGFR < 30 ml/min/1.73m² (MDRD4) - History of Hypersensitivity to everolimus, sirolimus or excipients - History of Hypersensitivity to macrolides - Pregnancy and breast feeding - Childbearing age women without efficient contraception - Law protected patients - Patients in emergency unable to express their consent - History of Hypersensitivity to cyclosporine or St-John's wort, stiripentol, bosentan, rosuvastatin - History of Hypersensitivity to tacrolimus, macrolides or excipients - History of Hypersensitivity to azathioprine - History of Hypersensitivity to mycophénolate mofetil or excipients

Additional Information

Official title COREV : A Multi-center, Randomized, Open-label Study Evaluating the Efficacy on Renal Function of Everolimus in Heart Transplant Recipients With Established Chronic Renal Failure
Principal investigator Pascale BOISSONNAT, MD
Trial information was received from ClinicalTrials.gov and was last updated in March 2012.
Information provided to ClinicalTrials.gov by Hospices Civils de Lyon.