Myocardial InfarctionESMO-VASCMINCT06376630
Study of Microvascular Dysfunction, CFR and Cardioprotective Effect of Early Administration of Esmolol in MI
A study testing Esmolol Hcl 10Mg/Ml Inj in people with Myocardial Infarction and Coronary Stenosis, run by National Medical Research Center for Cardiology, Ministry of Health of Russian Federation at 1 site in Russia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myocardial Infarction, Coronary Stenosis, Coronary Microvascular Dysfunction
- What is being tested?
- Esmolol Hcl 10Mg/Ml Inj
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteRussia
- Study dates
- 29 Jan 2024to 29 Jan 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- Diagnosed MI, completed PCI for the IRA and multivessel Coronary Artery Disease with diameter stenosis of 50-85% in non-IRA.
- Signed Informed Consent to participate in the study
Who cannot join
- 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;
Show all 29Show fewer
- 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;
- ECG evidence of spontaneous reperfusion on admission;
- patient's refusal from participation in the study.
- Substudy investigating coronary physiology
- History of coronary artery bypass grafting surgery;
- Non-IRA lesions resulting in diameter stenosis of below 50% and above 85%, main left coronary artery (LCA) stenosis above 50%;
- Chronic kidney disease stage 3b or above (glomerular filtration rate below 45 mL/min/m2 according to the CKD-EPI equation);
- History of a contrast-induced nephropathy (CIN) or a high CIN risk (calculated using the Mehran score);
- History of allergies to iodine-containing medications;
- Pregnancy or lactation;
- Left ventricle ejection fraction ≤ 30%;
- Known severe comorbidities independently affecting prognosis (chronic renal or liver failure, active malignancies etc.);
- Early post-infarction angina;
- Severe dementia;
- Patient's refusal from participation in the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Russia1 site, 1 recruiting
- Recruiting
NMRCCardiologyRu
Moscow
Andrey Komarov, PhD
Tatiana Sukhinina, PhD
About this study
Official title: Study of Microvascular Dysfunction, Coronary Flow Reserve and Cardioprotective Effect of Early Intravenously Administration of Esmolol in Patients With Myocardial Infarction
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.
Read more
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.
Read the detailed description
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.
Substudy of early esmolol administration: On admission patients will undergo ECG and echocardiography in an intensive care ward, according to standard clinical practice. Eligible patients having signed the Informed Consent Form will be randomized 1:1 by appropriate software. In the esmolol arm the infusion will begin immediately on admission simultaneously with conventional upfront treatment. Study procedures will be performed in parallel to the patient's preparation for the catheterization lab and transportation for primary PCI, without any delay of time to the catheterization lab. During the hospitalization cardiac MRI will be done with contrast enhancement using an ultraconducting MRI scanner with the magnetic field intensity of 1.5 T (Siemens Avanto). The following elements will be done without contrast enhancement:
- cine imaging MRI in standard views (long axis 2- and 4-chamber views, LV short axis) measuring left ventricle end diastolic volume (LV EDV), left ventricle end systolic volume (LV ESV), LV EF, regional wall motion abnormality across 17 LV segments;
- Т2-weighed images (T2WI) using the same views to assess myocardial edema (signal intensity elevation more than 2-fold compared to the normal myocardium).
For contrast enhancement a gadolinium-based contrast agent will be used (gadobutrol, Bayer) in the dose of 0.15 mmol/kg body weight. The following elements will be done with contrast enhancement:
- early contrast enhancement (2 minutes after intravenous administration of the contrast agent);
- delayed contrast enhancement (10 - 20 minutes after intravenous administration of the contrast agent).
The areas demonstrating with contrast enhancement will be assessed as areas of acute or chronic myocardial injury (during the presence of edema, according to T2WI results).
Substudy investigating coronary physiology. This substudy is expected to include 200 patients with MI and multivessel Coronary Artery Disease who will be found on PCI (performed for the IRA) to have lesions with diameter stenosis of 50-85% in other arteries.
During hospitalization for AMI treatment and diagnostic evaluation of patients will be done according to current clinical practice guidelines. All patients enrolled into the study will undergo PCI with IRA stenting. In the STEMI group, 50 hemodynamically stable patients after primary PCI will undergo invasive measurements of coronary hemodynamical parameters: instantaneous wave-free ratio, Pd/Pa, FFR with papaverine administration both into the IRA and into non-IRA (FFR measurements with papaverine administration will only be performed in patients without contraindications to such administrations [as worded for AMI patients as a separate exclusion criterion]). During the hospitalization those 50 patients will undergo cardiac MRI with IV contrast enhancement to evaluate MVO, beyond routine assessments.
Other 150 patients enrolled into the study (50 with STEMI and 100 with NSTEMI) during their first hospitalization for AMI will only undergo routine assessments and treatment procedures according to clinical practice guidelines. In 30-40 days after the MI patients will be hospitalized again. During their second hospitalization patients will undergo stress SPECT myocardial perfusion imaging or exercise stress echocardiography with physical exertion or ATP infusion, with CFR measurement, unless contraindicated. All patients will undergo a follow-up coronary angiography with invasive measurement of coronary hemodynamical parameters in non-IRA, accompanied by an assessment of IRA stenting outcomes (instantaneous wave-free ratio, Pd/Pa, unless contraindicated - FFR with papaverine administration etc.). If non-IRA stenting is indicated, PCI with subsequent invasive re-assessment of coronary hemodynamical parameters. The CFR value across the coronary artery basins will be calculated based on the tridimensional reconstruction of coronary arteries and intracoronary pressure measurements before and after stenting. In the subgroup of patients who underwent measurements of coronary hemodynamical parameters in the acute setting, follow-up measurements of coronary hemodynamical parameters will be performed. Subsequently relationship will be evaluated between invasive measurements of coronary hemodynamical parameters and the presence of MVO. Also, results of stress tests will be compared to invasive measurements of coronary hemodynamical parameters. Patients demonstrating CFR reduction in a stress echocardiography with ATP infusion will be asked to repeat a stress test within 1 month post-stenting, during a hospitalization, or on an out-patient visit within one month after discharge from the hospital.
- Being tested
- Esmolol Hcl 10Mg/Ml Inj
- Medical subject headings
- Myocardial Infarction, Coronary Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Esmolol Hcl 10Mg/Ml InjDrug
Also called Esmolol
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 group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Through study completion, an average of 2 years
Secondary outcomes (2)
Degree of microvascular obstruction
Evaluation by MRI with gadolinium delayed enhancement
Measured: During the week after myocardial infarction
Infarct size
Evaluation by MRI with gadolinium delayed enhancement
Measured: During the week after myocardial infarction
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2024
- Study start29 Jan 2024
- Primary completion29 Jan 2029 (estimated)
- Study completion29 Jan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Myocardial InfarctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Dmitry Pevzner, National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
- Investigators
- Dmitry Pevzner, MD, Principal investigator, National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06376630
- Sponsor's protocol ID
- 298-2024
- Acronym
- ESMO-VASCMI
- Status last verified
- Apr 2024
- First submitted
- 10 Apr 2024
- Last updated
- 19 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 37002468Garcia-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.
PubMed 27052688Er 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.
PubMed 26847114Clemente-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.
PubMed 33026079Van 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.
PubMed 22244483Anderson 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.
PubMed 32438987Kelshiker 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.
PubMed 34849697Lee 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.
PubMed 36338358Hausenloy 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.
PubMed 30428011Csippa 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.
PubMed 34622434Terenicheva 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.
PubMed 33734055Terenicheva 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.
PubMed 36286787Terenicheva 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.
PubMed 36286807
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Microvascular Dysfunction, Coronary Flow Reserve and Cardioprotective Effect of Early Intravenously Administration of Esmolol in Patients With Myocardial Infarction
- ClinicalTrials.gov ID
- NCT06376630
- Acronym / sponsor ID
- ESMO-VASCMI / 298-2024
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- National Medical Research Center for Cardiology, Ministry of Health of Russian FederationOther government
- Study start
- 29 Jan 2024 (actual)
- Primary completion
- 29 Jan 2029 (estimated)
- Study completion
- 29 Jan 2030 (estimated)
- First posted
- 19 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Substudy of early esmolol administration: On admission patients will undergo ECG and echocardiography in an intensive care ward, according to standard clinical practice. Eligible patients having signed the Informed Consent Form will be randomized 1:1 by appropriate software. In the esmolol arm the infusion will begin immediately on admission simultaneously with conventional upfront treatment. Study procedures will be performed in parallel to the patient's preparation for the catheterization lab and transportation for primary PCI, without any delay of time to the catheterization lab. During the hospitalization cardiac MRI will be done with contrast enhancement using an ultraconducting MRI scanner with the magnetic field intensity of 1.5 T (Siemens Avanto). The following elements will be done without contrast enhancement:
- cine imaging MRI in standard views (long axis 2- and 4-chamber views, LV short axis) measuring left ventricle end diastolic volume (LV EDV), left ventricle end systolic volume (LV ESV), LV EF, regional wall motion abnormality across 17 LV segments;
- Т2-weighed images (T2WI) using the same views to assess myocardial edema (signal intensity elevation more than 2-fold compared to the normal myocardium).
For contrast enhancement a gadolinium-based contrast agent will be used (gadobutrol, Bayer) in the dose of 0.15 mmol/kg body weight. The following elements will be done with contrast enhancement:
- early contrast enhancement (2 minutes after intravenous administration of the contrast agent);
- delayed contrast enhancement (10 - 20 minutes after intravenous administration of the contrast agent).
The areas demonstrating with contrast enhancement will be assessed as areas of acute or chronic myocardial injury (during the presence of edema, according to T2WI results).
Substudy investigating coronary physiology. This substudy is expected to include 200 patients with MI and multivessel Coronary Artery Disease who will be found on PCI (performed for the IRA) to have lesions with diameter stenosis of 50-85% in other arteries.
During hospitalization for AMI treatment and diagnostic evaluation of patients will be done according to current clinical practice guidelines. All patients enrolled into the study will undergo PCI with IRA stenting. In the STEMI group, 50 hemodynamically stable patients after primary PCI will undergo invasive measurements of coronary hemodynamical parameters: instantaneous wave-free ratio, Pd/Pa, FFR with papaverine administration both into the IRA and into non-IRA (FFR measurements with papaverine administration will only be performed in patients without contraindications to such administrations [as worded for AMI patients as a separate exclusion criterion]). During the hospitalization those 50 patients will undergo cardiac MRI with IV contrast enhancement to evaluate MVO, beyond routine assessments.
Other 150 patients enrolled into the study (50 with STEMI and 100 with NSTEMI) during their first hospitalization for AMI will only undergo routine assessments and treatment procedures according to clinical practice guidelines. In 30-40 days after the MI patients will be hospitalized again. During their second hospitalization patients will undergo stress SPECT myocardial perfusion imaging or exercise stress echocardiography with physical exertion or ATP infusion, with CFR measurement, unless contraindicated. All patients will undergo a follow-up coronary angiography with invasive measurement of coronary hemodynamical parameters in non-IRA, accompanied by an assessment of IRA stenting outcomes (instantaneous wave-free ratio, Pd/Pa, unless contraindicated - FFR with papaverine administration etc.). If non-IRA stenting is indicated, PCI with subsequent invasive re-assessment of coronary hemodynamical parameters. The CFR value across the coronary artery basins will be calculated based on the tridimensional reconstruction of coronary arteries and intracoronary pressure measurements before and after stenting. In the subgroup of patients who underwent measurements of coronary hemodynamical parameters in the acute setting, follow-up measurements of coronary hemodynamical parameters will be performed. Subsequently relationship will be evaluated between invasive measurements of coronary hemodynamical parameters and the presence of MVO. Also, results of stress tests will be compared to invasive measurements of coronary hemodynamical parameters. Patients demonstrating CFR reduction in a stress echocardiography with ATP infusion will be asked to repeat a stress test within 1 month post-stenting, during a hospitalization, or on an out-patient visit within one month after discharge from the hospital.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Substudy evaluating cardioprotective effects of early iv administration of esmolol | Active comparator | Drug: Esmolol Hcl 10Mg/Ml Inj100 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 |
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
- Diagnosed MI, completed PCI for the IRA and multivessel Coronary Artery Disease with diameter stenosis of 50-85% in non-IRA.
- Signed Informed Consent to participate in the study
Key exclusion criteria (29 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Esmolol Hcl 10Mg/Ml InjAlso: Esmololthe 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. | Drug | Substudy evaluating cardioprotective effects of early iv administration of esmolol |
Primary outcome
Composite of adverse cardiac outcomes
Time frame: Through study completion, an average of 2 years
Congestive heart failure, episodes of recurrent congestive heart failure worsening resulting in hospitalizations, cardiac mortality, MI recurrences, unstable angina, urgent myocardial revascularization
2 secondary outcomes
Degree of microvascular obstruction
Time frame: During the week after myocardial infarction
Infarct size
Time frame: During the week after myocardial infarction
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2024.
- Background: PubMed 37002468Sun 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.
- Background: PubMed 27052688Garcia-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.
- Background: PubMed 26847114Er 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.
- Background: PubMed 33026079Clemente-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.
- Background: PubMed 22244483Van 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.
- Background: PubMed 32438987Anderson 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.
- Background: PubMed 34849697Kelshiker 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.
- Background: PubMed 36338358Lee 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.
- Background: PubMed 30428011Hausenloy 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.
- Background: PubMed 34622434Csippa 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.
- Background: PubMed 33734055Terenicheva 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.
- Background: PubMed 36286787Terenicheva 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Dmitry Pevzner, MD principal investigator
National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Esmolol Hcl 10Mg/Ml Inj in people with Myocardial Infarction and Coronary Stenosis, run by National Medical Research Center for Cardiology, Ministry of Health of Russian Federation at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Maria Terenicheva, MD (5874134 ext. +7905, starcad@bk.ru), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite of adverse cardiac outcomes (time frame: Through study completion, an average of 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06376630, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2024.