Concomitant Milrinone and Esmolol Treatment in Patients with Acute Myocardial Infarction

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.

Conditions

• Myocardial Reperfusion Injury

Interventions

DRUG

Milrinone

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

DRUG

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

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

Sponsors & Collaborators

• National University Hospital of Singapore

  collaborator UNKNOWN

• Shantou University Medical College

  lead OTHER

Principal Investigators

• Ming-He Huang, MD, PhD · Gulf Coast Heart Clinic, PLLC & University of Texas Medical Branch

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

90 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2015-05-31

Primary Completion

2023-03-31

Completion

2024-12-31

Countries

• Singapore

Study Locations