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

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

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

Study Overview

• Status: Completed
• Conditions: Chronic Renal Insufficiency; Cardiac Transplantation
• Intervention / Treatment: Drug: everolimus

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Lyon, France
    • Hospices Civils de Lyon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Pascale BOISSONNAT, MD, Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2008
• Primary Completion (Actual): April 17, 2014
• Study Completion (Actual): April 17, 2014

Study Registration Dates

• First Submitted: July 15, 2008
• First Submitted That Met QC Criteria: July 15, 2008
• First Posted (Estimate): July 16, 2008

Study Record Updates

• Last Update Posted (Actual): June 20, 2017
• Last Update Submitted That Met QC Criteria: June 19, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Everolimus; Chronic renal insufficiency; Cardiac transplantation
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Renal Insufficiency; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Everolimus
• Other Study ID Numbers: 2007.495