Clinical Trial: Concomitant Milrinone and Esmolol Treatment in Patients With Acute Myocardial Infarction
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: Concomitant Milrinone and Esmolol Treatment in Patients With Acute Myocardial Infarction
Brief Summary:
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.
Detailed Summary:
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 effe
Sponsor: Ming-He Huang
Current Primary Outcome: The primary endpoint is the infarct-size reduction as assessed by measurement of cardiac biomarker creatine kinase. [ Time Frame: 2 years ]
Original Primary Outcome: Same as current
Current Secondary Outcome: The secondary endpoints are the reduction of CK-MB or troponin I [ Time Frame: 2 years ]
Original Secondary Outcome: Same as current
Information By: Shantou University Medical College
Dates:
Date Received: March 25, 2014
Date Started: May 2015
Date Completion: December 2017
Last Updated: November 20, 2015
Last Verified: November 2015
