Clinical trial NCT00716573: Efficacy Study of Everolimus on Renal Function in Heart Transplant Recipients With Established Chronic Renal Failure
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cardiac Transplantation
Chronic Renal Insufficiency
Keywords: Cardiac transplantation
Chronic renal insufficiency
Everolimus
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2008-07-16
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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

Primary outcomes:
measure: Evaluation of the renal function, at 12 months after everolimus introduction and doses of anticalcineurins decrease.
timeFrame: 12 months
Secondary outcomes:
measure: Evaluation of the benefit of everolimus introduction on renal function at 24 months
timeFrame: 24 months
measure: Evaluation of the benefit of everolimus introduction on incidence of Major Adverse Cardiac Events (MACEs)
timeFrame: 24 months
measure: Evaluation of the benefit of everolimus introduction on incidence of cardiovascular risk factor (Arterial Tension, diabetes, dyslipidemia, proteinuria)
timeFrame: 24 months
measure: Evaluation of the benefit of everolimus introduction on incidence of treatment withdrawals
timeFrame: 24 months
measure: Evaluation of the benefit of everolimus introduction on incidence of treated acute rejection
timeFrame: 24 months
measure: Evaluation of the benefit of everolimus introduction on safety
timeFrame: 24 months
Other outcomes:
Locations:
city: Lyon
country: France
facility: Hospices Civils de Lyon
Study officials:
affiliation: Hospices Civils de Lyon
name: Pascale BOISSONNAT, MD
role: PRINCIPAL_INVESTIGATOR
References: