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

Sponsor

Hospices Civils de Lyon (Other)

Overall Status

Completed

CT.gov ID

NCT00716573

Collaborator

(none)

120

Enrollment

Location

Arms

Actual Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Cardiac Transplantation Chronic Renal Insufficiency	Drug: everolimus	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 16, 2008

Actual Primary Completion Date :

Apr 17, 2014

Actual Study Completion Date :

Apr 17, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Introduction of everolimus associated with CNI (ciclosporin or tacrolimus) reduction (50%) to the current immunosuppression schedule	Drug: everolimus 0,75 mg bid, 24 months Other Names: Certican
No Intervention: 2 Maintain of their current immunosuppressive therapy

Arm

Intervention/Treatment

Experimental: 1

Introduction of everolimus associated with CNI (ciclosporin or tacrolimus) reduction (50%) to the current immunosuppression schedule

Drug: everolimus

0,75 mg bid, 24 months

Other Names:

Certican

No Intervention: 2

Maintain of their current immunosuppressive therapy

Outcome Measures

Primary Outcome Measures

Evaluation of the renal function, at 12 months after everolimus introduction and doses of anticalcineurins decrease. [12 months]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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