Effect of Preliminary Administration of Cyclosporine (Sandimmun ®) on Different Markers of Cardiac Ischaemia Induced by Cardiopulmonary Bypass

Study Overview
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Brief Summary
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Observe the effect of preliminary cyclosporine administration on different markers of cardiac ischaemia led by the aortic cross-clamp during coronary artery bypass surgery with Cardiopulmonary bypass.

Detailed Description
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The coronary artery bypass surgery, in spite of substantial improvements during the last years, is still associated to a post-operative mortality and morbidity: myocardial infarction, heart failure, cardiac arrhythmia, renal failure, Stroke. These complications are often due to ischaemia - reperfusion injury event. Recent studies showed that in case of cellular stress (in particular during the reperfusion after ischaemia) a not specific pore, called Mitochondrial permeability transition Pore (MPTP), could be opened. That caused the loss of ion homeostasis, then cell death as well as by apoptosis as by necrosis. Prevent the opening of this MPTP during the myocardial reperfusion after coronary bypass, for example, is an important objective to improve the cardioprotection. The Cyclosporin A, prevents the MPTP from opening. Several studies have shown an cytoprotection led by cyclosporin A, after ischaemia reperfusion in several models as isolated rats heart, in vivo rats heart and ex vivo myocardial ( atrial ) human tissues. Recently, a multicentric study performed in humans, during the acute phase of myocardial infarction, showed a reduction of infarct size by approximately 40% in the cyclosporine group compared to control group.

Official Title
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Double-Blind Phase II Pilot Monocentric Randomized Clinical Trial Evaluating the Effect of a Preliminary Administration of Cyclosporine on Different Markers of Cardiac Ischemia Led by the Aortic Cross-clamp During Coronary Artery Bypass Surgery With Cardiopulmonary Bypass.

Conditions
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Coronary Artery Bypass Surgery, Cardiopulmonary Bypass

Intervention / Treatment
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* Drug: Sandimmum
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient hospitalized for a coronary artery bypass surgery Not urgent surgery Left ventricular ejection fraction (LVEF)> 40 % 18 years and older patient who have sign the informed consent form Affiliation to the French Social Security. Exclusion Criteria: Beating heart surgery with or without Cardiopulmonary Bypass Patient receiving another surgical gesture combined to the CABG Myocardial infarction or vascular cerebral attack less than 30 days Previous History of cardiac surgery; Renal failure (creatinine > 200 µmol/l) Uncontrolled hypertension hyperkaliemy; hyperuricemy; Acute Coronary Syndrome Malignant tumor Unchecked infection Previous intravenous administration of Sandimmun ®; allergy to ciclosporin, ethyl alcohol, castor oil or nitrogen Pregnant Woman, parturient without contraception, or breast-feeding Age < 18 years Patient who have not signed the form of consent; Patient Under guardianship or being the object of a legal protective measure

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: cyclosporin<br>Intravenous cyclosporin injection. | Drug: Sandimmum<br>* Intravenous injection of cyclosporine<br>|
| Placebo Comparator: Pacebo<br>Intravenous injection of NaCl solution. | Drug: Placebo<br>* Intravenous Injection of NaCl solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under curve and maximal blood level of both troponin-T and Creatine Kinase-MB after cardiopulmonary bypass |  | at anaesthesia (ti), at the end of the cardiopulmonary bypass (t0), and 6 h, 12 h, 24 h,48h and 72h after the end of the cardiopulmonary bypass. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under curve and maximal blood level of S100β protein |  | at anaesthesia (ti), at the end of the cardiopulmonary bypass (t0), and 6 h, 12 h, 24 h,48h and 72h after the end of the cardiopulmonary bypass | 
| Spontaneous defibrillation at aorta declamping; Post surgical atrial fibrillation; ECG (new Q wave); Transthoracic Echocardiogram (diastolic and systolic function study, research of paradoxical septal motion, study of cardiac output)....) |  | until Day 3 after the end of the cardiopulmonary bypass | 
| Levels of inflammatory cytokines (TNF alpha , IL-1 alpha et IL-1 beta, IL-6, IL-8, IL-10). C-reactive protein (CRP) level |  | until day 8 after the end of the cardiopulmonary bypass | 
| Creatine blood levels |  | until 3 months after the end of the cardiopulmonary bypass | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronary artery bypass graft surgery (CABG), Cardiopulmonary Bypass (CPB), Cyclosporine, ischaemia reperfusion