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

Sponsor
National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
Study ID
NCT06376630
Status
Recruiting
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Conditions

  • Coronary Microvascular Dysfunction
  • Coronary Stenosis
  • Myocardial Infarction

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Esmolol Hcl 10Mg/Ml Inj — DRUG
    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.

Study Details

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.

Key Dates

First listed
Apr 19, 2024
Start date
Jan 29, 2024
Status verified
Apr 2024
Primary completion
Jan 29, 2029
Completion
Jan 29, 2030

Study Design

Enrollment
300 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Substudy evaluating cardioprotective effects of early iv administration of esmolol
    100 pts with STEMI will be randomized 1:1 in arms receiving esmolol or no IV beta-blockers. In the esmolol arm the infusion will begin immediately on admission
  • No Intervention: Substudy investigating coronary physiology
    50 stable patients with MI will undergo invasive measurements of coronary physiology. Those will also undergo cardiac MRI. Other 150 pts will not undergo invasive measurements of coronary physiology during initial hospitalization. Pts in both groups will be hospitalized again in 30-40 days after MI. They will undergo stress SPECT or stress echocardiography. All patients will undergo a follow-up coronary angiography with invasive measurement of coronary physiology

Primary Outcome Measure

Composite of adverse cardiac outcomes [ Time Frame: Through study completion, an average of 2 years ]

Central Contacts

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