Study of Microvascular Dysfunction, CFR and Cardioprotective Effect of Early Administration of Esmolol in MI

Summary

Study rationale: to evaluate clinical and prognostic relevance of microvascular dysfunction, coronary flow reserve and cardioprotective effects of iv administration of esmolol in patients with myocardial infarction.

First substudy is an open randomized trial evaluating the efficacy and safety of early intravenous administration of esmolol in patients with acute ST-segment elevation myocardial infarction (MI) and relative contraindications to administration of other intravenous β1-adrenergic blocker (metoprolol etс.). Сomparison group will include patients who have not received intravenous β1-adrenergic blocker. Secondary outcome in this substudy is the degree of microvascular obstruction and infarct size according to MRI with gadolinium delayed enhancement.

Second substudy examines the quantitative parameters of coronary physiology in patients with MI and multivessel disease. Changes of coronary physiology measurements over time ((iFR, Pd/Pa, FFR, delta FFR, gradient FFR per time unit (dFFR(t)/dt), pullback pressure gradient (PPG)) measured in the infarct-related artery and in non-infarct-related arteries with diameter stenosis of 50-85% immediately after the completion of a primary percutaneous coronary intervention and during a second hospitalization (30-45 days after STEMI) will be evaluated. The comparison changes of coronary physiology over time with presence of an MVO and infarct size determined by MRI. The model of calculating coronary flow reserve (CFR) based on tridimensional reconstruction of coronary arteries and coronary physiology parameters as measured during coronary angiography will be developed. The influence of coronary physiology parameters measured after complete myocardial revascularization by PCI, and derived CFR in patients with MI on long-term clinical outcomes will be evaluated, based on prospective data collection.

Primary composite outcome in all substudies will be the sum of adverse cardiac outcomes (congestive heart failure, episodes of recurrent congestive heart failure worsening resulting in hospitalizations, cardiac mortality, MI recurrences, unstable angina, urgent myocardial revascularization) within \> 12 months post-infarction.

Secondary composite outcome in all substudies is the degree of microvascular obstruction and infarct size evaluated by MRI with gadolinium delayed enhancement.

Conditions

• Myocardial Infarction
• Coronary Stenosis
• Coronary Microvascular Dysfunction

Interventions

DRUG

Esmolol Hcl 10Mg/Ml Inj

the loading dose of 500 mkg/kg for 1 minute, followed by the initial rate of 50 mkg/kg/min. Individual titration depending on the desired hemodynamical effect (to the heart rate of 60 bpm or to the maximum tolerated dose maintaining stable hemodynamics) every 5-15 minutes (the maximum allowed rate of administration is 300 mkg/kg/min) for 6 hours. Thereafter patients in both treatment arms - the IV esmolol arm and the placebo arm, will be administered oral β-adrenergic blockers, if decided so by the treating physician and unless contraindicated.

Sponsors & Collaborators

• National Medical Research Center for Cardiology, Ministry of Health of Russian Federation

  lead OTHER_GOV

Principal Investigators

• Dmitry Pevzner, MD · National Medical Research Center for Cardiology, Ministry of Health of Russian Federation

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-01-29

Primary Completion

2029-01-29

Completion

2030-01-29

Countries

• Russia

Study Locations