Ignite Creation Date:
2024-05-06 @ 8:26 PM
Last Modification Date:
2024-10-26 @ 3:27 PM
Study NCT ID:
NCT06376630
Status:
RECRUITING
Last Update Posted:
2024-04-19
First Post:
2024-04-10
Brief Title:
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
Organization:
National Medical Research Center for Cardiology Ministry of Health of Russian Federation
Study Overview
Official Title:
Study of Microvascular Dysfunction Coronary Flow Reserve and Cardioprotective Effect of Early Intravenously Administration of Esmolol in Patients With Myocardial Infarction
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ESMO-VASCMI
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 PdPa FFR delta FFR gradient FFR per time unit dFFRtdt 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
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 PdPa FFR delta FFR gradient FFR per time unit dFFRtdt 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 11 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 patients 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 15 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 015 mmolkg 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 PdPa 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 PdPa 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
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 11 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 patients 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 15 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 015 mmolkg 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 PdPa 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 PdPa 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None