Cardiac Transplantation, Chronic Renal Insufficiency
Conditions
Keywords
Cardiac transplantation, Chronic renal insufficiency, Everolimus
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
Interventions
DRUGeverolimus
0,75 mg bid, 24 months
Sponsors
Hospices Civils de Lyon
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Evaluation of the renal function, at 12 months after everolimus introduction and doses of anticalcineurins decrease. | 12 months |
Secondary
| Measure | Time frame |
|---|---|
| Evaluation of the benefit of everolimus introduction on safety | 24 months |
| 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 treated acute rejection | 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 Major Adverse Cardiac Events (MACEs) | 24 months |
Countries
France
Outcome results
None listed