Efficacy Study of Everolimus on Renal Function in Heart Transplant Recipients With Established Chronic Renal Failure

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Cardiac Transplantation, Chronic Renal Insufficiency

Intervention / Treatment
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* Drug: everolimus


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Introduction of everolimus associated with CNI (ciclosporin or tacrolimus) reduction (50%) to the current immunosuppression schedule | Drug: everolimus<br>* 0,75 mg bid, 24 months<br>* Other names: Certican;|
| No Intervention: 2<br>Maintain of their current immunosuppressive therapy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the renal function, at 12 months after everolimus introduction and doses of anticalcineurins decrease. |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the benefit of everolimus introduction on renal function at 24 months |  | 24 months | 
| Evaluation of the benefit of everolimus introduction on incidence of Major Adverse Cardiac Events (MACEs) |  | 24 months | 
| Evaluation of the benefit of everolimus introduction on incidence of cardiovascular risk factor (Arterial Tension, diabetes, dyslipidemia, proteinuria) |  | 24 months | 
| Evaluation of the benefit of everolimus introduction on incidence of treatment withdrawals |  | 24 months | 
| Evaluation of the benefit of everolimus introduction on incidence of treated acute rejection |  | 24 months | 
| Evaluation of the benefit of everolimus introduction on safety |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac transplantation, Chronic renal insufficiency, Everolimus