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.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Area under curve and maximal blood level of both troponin-T and Creatine Kinase-MB after cardiopulmonary bypass
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Pacebo
Intravenous injection of NaCl solution.
干预措施: Placebo (Drug)
cyclosporin
Intravenous cyclosporin injection.
干预措施: Sandimmum (Drug)
结局指标
主要结局
Area under curve and maximal blood level of both troponin-T and Creatine Kinase-MB after cardiopulmonary bypass
时间窗: 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.
次要结局
- 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)
- 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)
- 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)
- Creatine blood levels(until 3 months after the end of the cardiopulmonary bypass)