Efficacy Study of Everolimus on Renal Function in Heart Transplant Recipients With Established Chronic Renal Failure (COREV)
Primary Purpose
Cardiac Transplantation, Chronic Renal Insufficiency
Status
Completed
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
everolimus
Sponsored by
About this trial
This is an interventional treatment trial for Cardiac Transplantation focused on measuring Cardiac transplantation, Chronic renal insufficiency, Everolimus
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
Sites / Locations
- Hospices Civils de Lyon
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
1
2
Arm Description
Introduction of everolimus associated with CNI (ciclosporin or tacrolimus) reduction (50%) to the current immunosuppression schedule
Maintain of their current immunosuppressive therapy
Outcomes
Primary Outcome Measures
Evaluation of the renal function, at 12 months after everolimus introduction and doses of anticalcineurins decrease.
Secondary Outcome Measures
Evaluation of the benefit of everolimus introduction on renal function at 24 months
Evaluation of the benefit of everolimus introduction on incidence of Major Adverse Cardiac Events (MACEs)
Evaluation of the benefit of everolimus introduction on incidence of cardiovascular risk factor (Arterial Tension, diabetes, dyslipidemia, proteinuria)
Evaluation of the benefit of everolimus introduction on incidence of treatment withdrawals
Evaluation of the benefit of everolimus introduction on incidence of treated acute rejection
Evaluation of the benefit of everolimus introduction on safety
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00716573
Brief Title
Efficacy Study of Everolimus on Renal Function in Heart Transplant Recipients With Established Chronic Renal Failure
Acronym
COREV
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
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
September 16, 2008 (Actual)
Primary Completion Date
April 17, 2014 (Actual)
Study Completion Date
April 17, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon
4. Oversight
Data Monitoring Committee
Yes
5. 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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiac Transplantation, Chronic Renal Insufficiency
Keywords
Cardiac transplantation, Chronic renal insufficiency, Everolimus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
120 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
Introduction of everolimus associated with CNI (ciclosporin or tacrolimus) reduction (50%) to the current immunosuppression schedule
Arm Title
2
Arm Type
No Intervention
Arm Description
Maintain of their current immunosuppressive therapy
Intervention Type
Drug
Intervention Name(s)
everolimus
Other Intervention Name(s)
Certican
Intervention Description
0,75 mg bid, 24 months
Primary Outcome Measure Information:
Title
Evaluation of the renal function, at 12 months after everolimus introduction and doses of anticalcineurins decrease.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Evaluation of the benefit of everolimus introduction on renal function at 24 months
Time Frame
24 months
Title
Evaluation of the benefit of everolimus introduction on incidence of Major Adverse Cardiac Events (MACEs)
Time Frame
24 months
Title
Evaluation of the benefit of everolimus introduction on incidence of cardiovascular risk factor (Arterial Tension, diabetes, dyslipidemia, proteinuria)
Time Frame
24 months
Title
Evaluation of the benefit of everolimus introduction on incidence of treatment withdrawals
Time Frame
24 months
Title
Evaluation of the benefit of everolimus introduction on incidence of treated acute rejection
Time Frame
24 months
Title
Evaluation of the benefit of everolimus introduction on safety
Time Frame
24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pascale BOISSONNAT, MD
Organizational Affiliation
Hospices Civils de Lyon
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospices Civils de Lyon
City
Lyon
Country
France
12. IPD Sharing Statement
Learn more about this trial
Efficacy Study of Everolimus on Renal Function in Heart Transplant Recipients With Established Chronic Renal Failure
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