Concomitant Milrinone and Esmolol Treatment in Patients with Acute Myocardial Infarction

NCT02098629 | Completed Phase 2 DMC

• 1 other identifier: GCHC-14
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Myocardial Reperfusion Injury

Keywords

Myocardial infarction; myocardial ischemia; reperfusion injury

Outcome Measures

Primary Outcomes (1)

• Effects of Combination Therapy of Esmolol+Milrinone on Infarct Size

  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.

  6 months

Secondary Outcomes (1)

• Effects of combination therapy of esmolol+milrinone on long-term heart falure-related hospital admission and cardiac death

  5 years

Study Arms (2)

Milrinone+Esmolol

ACTIVE COMPARATOR

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: Milrinone; Drug: Esmolol

Saline infusion

PLACEBO COMPARATOR

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.

Drug: Saline Infusion

Interventions

Milrinone DRUG

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

Also known as: Primacor

Milrinone+Esmolol

Esmolol DRUG

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

Also known as: Brevibloc

Milrinone+Esmolol

Saline Infusion DRUG

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

Saline infusion

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shantou University Medical College: lead
• National University Hospital of Singapore: collaborator

Study Sites (1)

National University Hospital, Singapore

Singapore, 119077, Singapore

Location

Related Publications (2)

• Huang MH, Wu Y, Nguyen V, Rastogi S, McConnell BK, Wijaya C, Uretsky BF, Poh KK, Tan HC, Fujise K. Heart protection by combination therapy with esmolol and milrinone at late-ischemia and early reperfusion. Cardiovasc Drugs Ther. 2011 Jun;25(3):223-32. doi: 10.1007/s10557-011-6302-z.

  PMID: 21562974 BACKGROUND

• Poh KK, Xu X, Chan MY, Lee CH, Tay EL, Low AF, Chan KH, Sia W, Tang LQ, Tan HC, Lui CY, Nguyen V, Fujise K, Huang MH. Safety of combination therapy with milrinone and esmolol for heart protection during percutaneous coronary intervention in acute myocardial infarction. Eur J Clin Pharmacol. 2014 May;70(5):527-30. doi: 10.1007/s00228-014-1650-9. Epub 2014 Jan 25.

  PMID: 24463539 BACKGROUND

MeSH Terms

Conditions

Myocardial Reperfusion Injury; Myocardial Infarction; Myocardial Ischemia; Reperfusion Injury

Interventions

Milrinone; esmolol

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infarction; Ischemia; Necrosis

Intervention Hierarchy (Ancestors)

Amrinone; Aminopyridines; Amines; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Ming-He Huang, MD, PhD

  Gulf Coast Heart Clinic, PLLC & University of Texas Medical Branch

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director, Gulf Coast Heart Clinic

Study Record Dates

• First Submitted: March 25, 2014
• First Posted: March 28, 2014
• Study Start: May 1, 2015
• Primary Completion: March 1, 2023
• Study Completion: December 1, 2024
• Last Updated: January 9, 2025

Record last verified: 2024-10

Locations

SG (1)