Concomitant Milrinone and Esmolol Treatment in Patients with Acute Myocardial Infarction
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Effects of Combination Therapy of Esmolol+Milrinone on Infarct Size
研究概览
简要总结
Heart attack is the leading cause of death in the developed world. Following heart attack, re-establishing blood flow in a clogged heart vessel using percutaneous coronary intervention (PCI) is the standard of care. This therapy is called reperfusion therapy. Unfortunately, reperfusion therapy itself poses additional heart muscle damaging effect, a process called reperfusion injury. Excessive reperfusion injury can offset the net benefit of heart vessel blood flow restoration in patients with heart attacks. For those heart attack survivors, massive reperfusion injury can contribute to heart failure which carries high risk for death and long-term disabilities. To date, there is no drug available that can reduce reperfusion injury in heart attack patients.
Our group has demonstrated in a preclinical study that combining two available medications (milrinone and esmolol) when given right before the onset of reperfusion therapy greatly reduces heart muscle damage in an animal heart attack model. Furthermore, in a clinical safety, we demonstrated that combination therapy with milrinone and esmolol is safe in patients with heart attack undergoing PCI. If the heart-protective effect observed in our preclinical study can be replicated in human subjects, this proposed therapy will become the first of this kind to treat clinical reperfusion injury.
The present trial is a proof-of-concept study to determine whether the combination administration of milrinone and esmolol at the onset of reperfusion reduces the heart muscle damage in heart attack patients who receive reperfusion therapy with PCI.
详细描述
BACKGROUND AND RATIONALE
Acute myocardial infarction (AMI) is the leading cause of death in the developed world. Following AMI, reperfusion therapy with percutaneous coronary intervention (PCI) is the standard of care. PCI has been shown in meta-analyses to decrease mortality compared with thrombolysis. Despite this improvement in outcome, mortality after AMI remains 4-6% in general population. PCI has not been effective in reducing mortality in elderly patients. In fact, emergent reperfusion therapy may increase mortality in aging population. The worsening clinical outcome following reperfusion therapy in aging population suggests that reperfusion therapy per se actually exacerbates heart muscle damage, a well-defined clinical process called myocardial reperfusion injury. Reperfusion injury poses a continuous (hours to days) heart muscle damage process following PCI or thrombosis. Excessive reperfusion injury can offset the net benefit of coronary blood flow restoration in AMI patients. For those AMI survivors, massive heart muscle damage due to ischemia/reperfusion injury leads to congestive heart failure (CHF) which carries high risk for sudden death and long-term morbidity.
The inevitable lethal reperfusion injury following reperfusion remains an unsolved clinical problem. To date, there is no drug available that can reduce reperfusion injury associated with PCI or other modalities of coronary artery revascularization. A recent preclinical study from our group demonstrates that combination therapy with milrinone+esmolol when given before the onset of reperfusion reduces infarct-size in an animal model with AMI followed by reperfusion. In a phase I clinical trial from our team, it has been shown that combination therapy with milrinone+esmolol is safe in patients with AMI undergoing PCI. If the infarct-size-limiting effect observed in our preclinical data can be replicated in human subjects, this proposed therapy will become the first of this kind to treat clinical reperfusion injury.
The proposed project is a proof-of-concept study to determine whether the combination administration of milrinone+esmolol at the onset of reperfusion reduces the infarct size in patients with S-T elevation MI (STEMI).
STUDY METHODS
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
- Single (Investigator)
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women, 18 years of age or older, who present within 12 hours after the onset of chest pain, who has ST-segment elevation of more than 0.1 mV in two contiguous leads, and for whom the clinical decision is made to treat with PCI will be eligible for enrollment.
排除标准
- •Patients with cardiac arrest, ventricular fibrillation, cardiogenic shock, previous acute myocardial infarction will not included in the study. Patients with occlusion of the left main will be excluded. Patients with baseline heart rate <50 beats/min and systolic BP<90 mmHg and pregnant patients will excluded. Finally, patients who have any disorder that is associated with immunologic dysfunction (e.g., cancer, lymphoma, a positive serologic test for the human immunodeficiency virus, or hepatitis) more recently than 6 months before presentation will be excluded.
研究组 & 干预措施
Milrinone+Esmolol
Approximately 5 minutes before stent deployment, the patients in the milrinone+esmolol group start to receive continuous intravenous drug infusion for 10 minutes. Milrinone and esmolol (each in 10 ml volume) will be placed in two separate syringes being connected to their respective venous catheters.
Dosage of study drugs: Syringe #1 Milrinone 5 ug/kg/min Syringe #2 Esmolol 10 ug/kg/min
干预措施: Milrinone (Drug)
Milrinone+Esmolol
Approximately 5 minutes before stent deployment, the patients in the milrinone+esmolol group start to receive continuous intravenous drug infusion for 10 minutes. Milrinone and esmolol (each in 10 ml volume) will be placed in two separate syringes being connected to their respective venous catheters.
Dosage of study drugs: Syringe #1 Milrinone 5 ug/kg/min Syringe #2 Esmolol 10 ug/kg/min
干预措施: Esmolol (Drug)
Saline infusion
Approximately 5 minutes before stent deployment, the patients in the placebo group start to receive continuous intravenous saline infusion for 10 minutes. Two syringes containing saline (10 ml volume in each) will be connected to two separate venous catheters during the infusion.
干预措施: Saline Infusion (Drug)
结局指标
主要结局
Effects of Combination Therapy of Esmolol+Milrinone on Infarct Size
时间窗: 6 months
To investigate the efficacy of a combination therapy of milrinone and esmolol in mitigating acute reperfusion injury in ST-elevation myocardial infarction (STEMI) patients. After randomization, STEMI patients from both active and control groups underwent cardiac magnetic resonance (CMR) study at 5 days and 6 months post-infarction.
次要结局
- Effects of combination therapy of esmolol+milrinone on long-term heart falure-related hospital admission and cardiac death(5 years)
研究者
Ming-He Huang
Medical Director, Gulf Coast Heart Clinic
Shantou University Medical College