Effect of Preliminary Administration of Cyclosporine (Sandimmun ®) on Different Markers of Cardiac Ischaemia Induced by Cardiopulmonary Bypass (Ciclo et CEC)
Coronary Artery Bypass Surgery
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
|Official Title:||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.|
- Area under curve and maximal blood level of both troponin-T and Creatine Kinase-MB after cardiopulmonary bypass [ Time Frame: 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. ] [ Designated as safety issue: Yes ]
- Area under curve and maximal blood level of S100β protein [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
- 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)....) [ Time Frame: until Day 3 after the end of the cardiopulmonary bypass ] [ Designated as safety issue: Yes ]
- Levels of inflammatory cytokines (TNF alpha , IL-1 alpha et IL-1 beta, IL-6, IL-8, IL-10). C-reactive protein (CRP) level [ Time Frame: until day 8 after the end of the cardiopulmonary bypass ] [ Designated as safety issue: Yes ]
- Creatine blood levels [ Time Frame: until 3 months after the end of the cardiopulmonary bypass ] [ Designated as safety issue: Yes ]
|Study Start Date:||April 2009|
|Study Completion Date:||July 2011|
|Primary Completion Date:||May 2011 (Final data collection date for primary outcome measure)|
Active Comparator: cyclosporin
Intravenous cyclosporin injection.
Intravenous injection of cyclosporine
Placebo Comparator: Pacebo
Intravenous injection of NaCl solution.
Intravenous Injection of NaCl solution
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01002859
|Department of cardiac surgery - University Hospital of Grenoble|
|Grenoble,, France, 38043|
|Principal Investigator:||Vincent BACH, MD||Cardiac Surgery Department - University Hospital of Grenoble,|