Intracoronary Injection of Melatonin for Patients With ST-elevation Myocardial Infarction: a Placebo Controlled Randomized Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 2
- 主要终点
- MRI of the heart
研究概览
简要总结
In Denmark, 12.000 people a year, is struck by acute myocardial infarction. A third of these cannot be saved before treatment is possible.
Despite quick and effective reperfusion of the coronary arteries using PCI (Percutaneous Coronary Intervention) after an acute ST-elevation myocardial infarction, substantial morbidity and mortality remain. Infarct size is an important determinant of the short-and long-term outcome after acute myocardial infarction. The most widely used and most effective proven therapy to limit infarct size is the early reperfusion induced by or PCI.
Although beneficial in terms of myocardial salvage, reperfusion itself may contribute to additional damage of the myocardium; the damage due to the combined processes is known as "ischemia-reperfusion injury". The pathogenesis of myocardial ischemia-reperfusion injury is a multifactorial process involving the interaction of multiple mechanisms. Numerous studies indicate that there are three pivotal factors in the pathogenesis of ischemia-reperfusion injury: elevated oxidative damage, depressed energy metabolism, and altered calcium homeostasis.
Partially reduced species of oxygen, including the superoxide anion radical, hydroxyl radical, and hydrogen peroxide, are generated intracellularly as by-product of oxygen metabolism. These reactive oxygen species cause peroxidation af membrane lipids, denaturation of proteins, and modification of DNA, all of which ultimately can lead to cell death. In mammals, cell damage induced by partially reduced oxygen species can also initiate local inflammatory responses, which then lead to further oxidant-mediated tissue injury.
Melatonin is mainly known for its role as an endogenously produced circadian hormone.
For the last twenty years, increasing evidence has proven melatonin to be a very potent direct and indirect antioxidant.
Recent experimental studies have documented the beneficial effects of melatonin in reducing tissue damage and limiting cardiac pathophysiology in models of experimental ischemia-reperfusion.
Primary hypothesis: Melatonin given to patients undergoing PCI can reduce the myocardial damage sustained by ischemia-reperfusion.
详细描述
Purpose The purpose of this Ph.D study is to examine the antioxidative effect of melatonin in relation to ischemia-reperfusion injury.
The investigators wish to examine to which extend melatonin administered to patients undergoing primary PCI for acute myocardial infarction will reduce the damage of the myocardium caused by ischemia-reperfusion injury and thereby hopefully improve the clinical outcome.
Theory and hypotheses Because there is strong evidence that free radicals contribute to post-ischemic injury, antioxidant enzyme therapy could potentially be extremely effective in reducing the cellular damage. In reality, however, the usefulness of this therapy is limited by a number of factors, in particular the ability of the antioxidants to penetrate the cell membrane and to scavenge free radicals in situ. Fortunately, this limitation can, in part, be addressed with the use of melatonin, a potent indirect and direct free radical scavenger that easily diffuses through the cell membrane to exert its antioxidant effects in all compartments of the cell. Indeed, in contrast to the partial of distribution of other antioxidants, such as vitamin C or E, the melatonin distributes it readily in all subcellular compartments owing to its double-solubility in both, aqueous and in lipid environment. Several recent publications present evidence that the newly discovered antioxidant melatonin has significant protective actions against the cardiac damage such as occurs during ischemia-reperfusion injury.
Primary hypothesis: Melatonin given to patients undergoing PCI can reduce the myocardial damage sustained by ischemia-reperfusion.
Inclusion:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Melatonin
The randomized patients will receive 10 ml 0,1 mg/ml melatonin intracoronarily and 49 mg intravenously.
干预措施: Melatonin, N-acetyl-5-methoxytryptamine (Drug)
Isotonic saline
The randomized patients will receive 10 ml isotonic saline (NaCl)and 490 ml intravenously.
干预措施: Isotonic saline, Natrium chloride (Drug)
结局指标
主要结局
MRI of the heart
时间窗: day 4 after pci (+/- 1 day)
Focusing on quantification infarct size, area at risk and myocardial salvage index
次要结局
- Oxidative markers in plasma(24 hours after pci)
- Creatinin Kinase Myocardial Band (CK-MB)(96 Hours after pci)
- High-sensitive Troponin T (Hs-TnT) or High-sensitive TnI(96 hours after pci)
- plasma level of melatonin(after pci)
- Clinical events(Within 90 days of pci)