Study to Evaluate Effect of Everolimus in Progression of Graft Vascular Illness on Patients With Heart Transplant

Study Overview
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Brief Summary
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The purpose of this study is to evaluate if there is a significantly less incidence of major clinical events due to graft vascular illness in recipients of a cardiac transplant on treatment with an immunosuppressive combination, which includes Everolimus, compared to those that continue the previously used immunosuppressive treatment.

Detailed Description
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This is a prospective, randomized, multicentre, open and controlled study, to evaluate the efficacy and safety of everolimus combined with cyclosporin for microemulsion and steroids according to medical judgement, opposite to the usual therapy which the patient already has received (typically: ciclosporin + azathioprine or mycophenolate mofetil + steroids according to the judgement of the doctor) for patients receiving a cardiac orthotopic transplant since at least 12 months. The patients will be randomized in a 2:1 proportion (everolimus:control), in order to make it possible for the majority of patients to receive the potentially active treatment in a lethal illness for which there is not efficient known treatment up to date. The study duration will be 2 years of follow-up for each patient. At the end of this period, the patients will be offered the possibility to maintain the immunosuppressive treatment to which they have been assigned, and periodic revisions will be made each 3-6 months. The two treatment groups are: Group I - Everolimus twice a day v.o. + cyclosporin for microemulsion in reduced doses +/- steroids. Group II - Cyclosporin for microemulsion + azathioprine or mycophenolate mofetil +/- steroids (the same administration schedule and medication which the patient received earlier).

Official Title
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Prospective and Randomized Study to Evaluate the Effect of Everolimus in the Clinical and Intra-Cardiac Ecography Progression of Heart Graft Vascular Illness.

Conditions
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Cardiac Transplant

Intervention / Treatment
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* Drug: everolimus
* Drug: azathioprine or mycophenolate mofetil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients suffering a heart transplantation at least 12 months before the inclusion. Patients with significant graft vascular cardiac illness. Exclusion Criteria: Patients who received more than one solid organ. Hypersensibility to everolimus. Patients with expected surviving less than 6 months. Analytic abnormality significant (platelets < 70.000 plat./mm3, WBC<4.000./mm3, creatinine > 2,5 mg/dl) Neoplasm and/or severe systemic illness. Mental significant illness. Patients who have received sirolimus or everolimus in any moment after transplant. Pregnant or lactating woman.

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>Everolimus 2 times per day + cyclosporin low dose +/- steroids | Drug: everolimus<br>* Everolimus 2 times per day, v.o., 2 years treatment.<br>* Other names: Certican;|
| Active Comparator: 2<br>Cyclosporin + azathioprine or mofetil mycophenolate +/- steroids (the same treatment that patient had before the study). | Drug: azathioprine or mycophenolate mofetil<br>* 2 times per day during 2 years<br>* Other names: Cellcept;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects that present at least one major clinical event due to graft vascular illness during the first year of the study on both treatment arms. |  | December 2010 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intra-coronary ultrasound, safety and adverse events, Nt-proBNP, left ventricular systolic function, coronary stenosis. |  | December 2010 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Effect of everolimus in graft vascular cardiac illness