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

NCT06376630 | Recruiting

• 1 other identifier: 298-2024
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief 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

Outcome Measures

Primary Outcomes (1)

• Composite 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

  Through study completion, an average of 2 years

Secondary Outcomes (2)

• Degree of microvascular obstruction

  During the week after myocardial infarction

• Infarct size

  During the week after myocardial infarction

Study Arms (2)

Substudy evaluating cardioprotective effects of early iv administration of esmolol

ACTIVE COMPARATOR

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

Drug: Esmolol Hcl 10Mg/Ml Inj

Substudy investigating coronary physiology

NO INTERVENTION

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

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.

Also known as: Esmolol

Substudy evaluating cardioprotective effects of early iv administration of esmolol

Eligibility Criteria

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

You may qualify if:

• Diagnosed acute ST elevation MI, type 1, within the first 8 hours of disease onset;
• Treating physician's decision not to administer metoprolol intravenously prior to primary PCI due to a high risk of complications (BP \< 120/80 mm Hg at baseline examination, moderate evidence of heart failure (Killip 2) or a risk of its development (LV EF ≤ 30%), first degree AV block with PQ ≥ 0.25 ms, history of asthma or severe COPD etc.)
• Signed Informed Consent to participate in the study

You may not qualify if:

• severe heart failure (pulmonary edema; SCAI В-Е cardiogenic shock);
• atrioventricular conduction abnormality higher than first degree, without a pacemaker;
• sinus bradycardia with the heart rate of \< 60 bpm;
• BP \< 100/60 mm Hg.;
• asthma in exacerbation;
• history of a STEMI in the IRA basin;
• clinically significant bleeding or hypovolemia;
• hypersensitivity to esmolol;
• pregnancy or lactation;
• known severe comorbidities independently affecting prognosis (Child Pugh class C liver failure, active malignancies etc.);
• contraindications to MRI (MR-incompatible pacemaker/implanted cardioverter-defibrillator, cochlear implants, clips on brain vessels, foreign metal objects - bullets, intraorbital metal fragments, insulin pumps, body weight above 150 kg, history of allergies to gadolinium, claustrophobia);
• severe dementia;
• known severe comorbidities independently affecting prognosis (chronic renal or liver failure, active malignancies etc.);
• complicated PCI, "no reflow" phenomenon on follow-up coronary angiography;
• thrombolysis for AMI;

Sponsors & Collaborators

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

Study Sites (1)

NMRCCardiologyRu

Moscow, Russia

RECRUITING

Related Publications (13)

• Sun B, Wang CY, Chen RR. Clinical Efficacy and Safety of Early Intravenous Administration of Beta-Blockers in Patients Suffering from Acute ST-Segment Elevation Myocardial Infarction Without Heart Failure Undergoing Primary Percutaneous Coronary Intervention: A Study-Level Meta-Analysis of Randomized Clinical Trials. Cardiovasc Drugs Ther. 2024 Aug;38(4):833-846. doi: 10.1007/s10557-023-07448-x. Epub 2023 Apr 1.

  PMID: 37002468 BACKGROUND

• Garcia-Ruiz JM, Fernandez-Jimenez R, Garcia-Alvarez A, Pizarro G, Galan-Arriola C, Fernandez-Friera L, Mateos A, Nuno-Ayala M, Aguero J, Sanchez-Gonzalez J, Garcia-Prieto J, Lopez-Melgar B, Martinez-Tenorio P, Lopez-Martin GJ, Macias A, Perez-Asenjo B, Cabrera JA, Fernandez-Ortiz A, Fuster V, Ibanez B. Impact of the Timing of Metoprolol Administration During STEMI on Infarct Size and Ventricular Function. J Am Coll Cardiol. 2016 May 10;67(18):2093-2104. doi: 10.1016/j.jacc.2016.02.050. Epub 2016 Apr 3.

  PMID: 27052688 BACKGROUND

• Er F, Dahlem KM, Nia AM, Erdmann E, Waltenberger J, Hellmich M, Kuhr K, Le MT, Herrfurth T, Taghiyev Z, Biesenbach E, Yuksel D, Eran-Ergoknil A, Vanezi M, Caglayan E, Gassanov N. Randomized Control of Sympathetic Drive With Continuous Intravenous Esmolol in Patients With Acute ST-Segment Elevation Myocardial Infarction: The BEtA-Blocker Therapy in Acute Myocardial Infarction (BEAT-AMI) Trial. JACC Cardiovasc Interv. 2016 Feb 8;9(3):231-240. doi: 10.1016/j.jcin.2015.10.035.

  PMID: 26847114 BACKGROUND

• Clemente-Moragon A, Gomez M, Villena-Gutierrez R, Lalama DV, Garcia-Prieto J, Martinez F, Sanchez-Cabo F, Fuster V, Oliver E, Ibanez B. Metoprolol exerts a non-class effect against ischaemia-reperfusion injury by abrogating exacerbated inflammation. Eur Heart J. 2020 Dec 7;41(46):4425-4440. doi: 10.1093/eurheartj/ehaa733.

  PMID: 33026079 BACKGROUND

• Van Herck PL, Paelinck BP, Haine SE, Claeys MJ, Miljoen H, Bosmans JM, Parizel PM, Vrints CJ. Impaired coronary flow reserve after a recent myocardial infarction: correlation with infarct size and extent of microvascular obstruction. Int J Cardiol. 2013 Jul 31;167(2):351-6. doi: 10.1016/j.ijcard.2011.12.099. Epub 2012 Jan 13.

  PMID: 22244483 BACKGROUND

• Anderson HVS. Acute Coronary Physiology. JACC Cardiovasc Interv. 2020 May 25;13(10):1168-1170. doi: 10.1016/j.jcin.2020.03.037. No abstract available.

  PMID: 32438987 BACKGROUND

• Kelshiker MA, Seligman H, Howard JP, Rahman H, Foley M, Nowbar AN, Rajkumar CA, Shun-Shin MJ, Ahmad Y, Sen S, Al-Lamee R, Petraco R; Coronary Flow Outcomes Reviewing Committee. Coronary flow reserve and cardiovascular outcomes: a systematic review and meta-analysis. Eur Heart J. 2022 Apr 19;43(16):1582-1593. doi: 10.1093/eurheartj/ehab775.

  PMID: 34849697 BACKGROUND

• Lee JM, Lee SH, Shin D, Choi KH, van de Hoef TP, Kim HK, Samady H, Kakuta T, Matsuo H, Koo BK, Fearon WF, Escaned J. Physiology-Based Revascularization: A New Approach to Plan and Optimize Percutaneous Coronary Intervention. JACC Asia. 2021 May 21;1(1):14-36. doi: 10.1016/j.jacasi.2021.03.002. eCollection 2021 Jun.

  PMID: 36338358 BACKGROUND

• Hausenloy DJ, Chilian W, Crea F, Davidson SM, Ferdinandy P, Garcia-Dorado D, van Royen N, Schulz R, Heusch G. The coronary circulation in acute myocardial ischaemia/reperfusion injury: a target for cardioprotection. Cardiovasc Res. 2019 Jun 1;115(7):1143-1155. doi: 10.1093/cvr/cvy286.

  PMID: 30428011 BACKGROUND

• Csippa B, Uveges A, Gyurki D, Jenei C, Tar B, Bugarin-Horvath B, Szabo GT, Komocsi A, Paal G, Koszegi Z. Simplified coronary flow reserve calculations based on three-dimensional coronary reconstruction and intracoronary pressure data. Cardiol J. 2023;30(4):516-525. doi: 10.5603/CJ.a2021.0117. Epub 2021 Oct 8.

  PMID: 34622434 BACKGROUND

• Terenicheva MA, Shakhnovich RM, Stukalova OV, Pevzner DV, Arutyunyan GK, Demchenkova AY, Merkulova IN, Ternovoy SK. Correlations between clinical and laboratory findings and prognostically unfavorable CMR-based characteristics of acute ST-elevation myocardial infarction. Kardiologiia. 2021 Feb 10;61(1):44-51. doi: 10.18087/cardio.2021.1.n1373. English, Russian.

  PMID: 33734055 BACKGROUND

• Terenicheva MA, Stukalova OV, Shakhnovich RM, Ternovoy SK. [The role of cardiac magnetic resonance imaging (cardiovascular magnetic resonance) in defining the prognosis of patients with acute ST-segment elevation myocardial infarction. Part 1. Indications and contraindications to cardiovascular magnetic resonance]. Ter Arkh. 2021 Apr 15;93(4):497-501. doi: 10.26442/00403660.2021.04.200687. Russian.

  PMID: 36286787 BACKGROUND

• Terenicheva MA, Stukalova OV, Shakhnovich RM, Ternovoy SK. [The role of cardiac magnetic resonance imaging in defining the prognosis of patients with acute ST-segment elevation myocardial infarction. Part 2. Assessment of the disease prognosis]. Ter Arkh. 2022 May 26;94(4):552-557. doi: 10.26442/00403660.2022.04.201458. Russian.

  PMID: 36286807 BACKGROUND

MeSH Terms

Conditions

Myocardial Infarction; Coronary Stenosis

Interventions

esmolol

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Coronary Disease

Study Officials

• Dmitry Pevzner, MD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maria Terenicheva, MD

CONTACT

5874134; starcad@bk.ru

Goar Arutunian, MD

CONTACT

7304068; argoar@yandex.ru

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: envelopes
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of the Emergency Cardiology Department

Model Details: 300 pts with MI are to be enrolled. Among them 100 pts with STEMI will be included into the substudy evaluating cardioprotective effects of early iv administration of esmolol. They will be randomized 1:1 by in arms receiving esmolol or no IV beta-blockers. In the esmolol arm the infusion will begin immediately on admission. 200 pts with MI and multivessel disease with non-IRA lesions of 50-85% diameter stenosis will be included into another substudy investigating coronary physiology. All patients will undergo PCI with IRA stenting. 50 stable patients 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.

Study Record Dates

• First Submitted: April 10, 2024
• First Posted: April 19, 2024
• Study Start: January 29, 2024
• Primary Completion (Estimated): January 29, 2029
• Study Completion (Estimated): January 29, 2030
• Last Updated: April 19, 2024

Record last verified: 2024-04

Locations

RU (1)