Ignite Creation Date:
2025-12-24 @ 11:56 PM
Ignite Modification Date:
2025-12-25 @ 9:53 PM
Study NCT ID:
NCT04573751
Status:
COMPLETED
Last Update Posted:
2024-04-29
First Post:
2020-09-28
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
The EPIVER Randomized Controlled Trial
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000072657', 'term': 'ST Elevation Myocardial Infarction'}, {'id': 'D054318', 'term': 'No-Reflow Phenomenon'}], 'ancestors': [{'id': 'D009203', 'term': 'Myocardial Infarction'}, {'id': 'D017202', 'term': 'Myocardial Ischemia'}, {'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D007238', 'term': 'Infarction'}, {'id': 'D007511', 'term': 'Ischemia'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D009336', 'term': 'Necrosis'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D059039', 'term': 'Standard of Care'}, {'id': 'D004837', 'term': 'Epinephrine'}, {'id': 'D014700', 'term': 'Verapamil'}, {'id': 'D005074', 'term': 'Evoked Potentials, Visual'}], 'ancestors': [{'id': 'D019984', 'term': 'Quality Indicators, Health Care'}, {'id': 'D011787', 'term': 'Quality of Health Care'}, {'id': 'D006298', 'term': 'Health Services Administration'}, {'id': 'D017530', 'term': 'Health Care Quality, Access, and Evaluation'}, {'id': 'D004983', 'term': 'Ethanolamines'}, {'id': 'D000605', 'term': 'Amino Alcohols'}, {'id': 'D000438', 'term': 'Alcohols'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D000588', 'term': 'Amines'}, {'id': 'D015306', 'term': 'Biogenic Monoamines'}, {'id': 'D001679', 'term': 'Biogenic Amines'}, {'id': 'D002395', 'term': 'Catecholamines'}, {'id': 'D002396', 'term': 'Catechols'}, {'id': 'D010636', 'term': 'Phenols'}, {'id': 'D001555', 'term': 'Benzene Derivatives'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D010627', 'term': 'Phenethylamines'}, {'id': 'D005021', 'term': 'Ethylamines'}, {'id': 'D005071', 'term': 'Evoked Potentials'}, {'id': 'D000071080', 'term': 'Cortical Excitability'}, {'id': 'D055724', 'term': 'Electrophysiological Phenomena'}, {'id': 'D010829', 'term': 'Physiological Phenomena'}, {'id': 'D009424', 'term': 'Nervous System Physiological Phenomena'}, {'id': 'D055687', 'term': 'Musculoskeletal and Neural Physiological Phenomena'}, {'id': 'D009799', 'term': 'Ocular Physiological Phenomena'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 104}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2020-12-30', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-04', 'completionDateStruct': {'date': '2024-01-31', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-04-26', 'studyFirstSubmitDate': '2020-09-28', 'studyFirstSubmitQcDate': '2020-09-28', 'lastUpdatePostDateStruct': {'date': '2024-04-29', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-10-05', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2023-01-31', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Mortality', 'timeFrame': 'month 1', 'description': 'Mortality rate (percent)'}, {'measure': 'New onset or worsening acute heart failure', 'timeFrame': 'month 1', 'description': 'The rate (percent) of patients experiencing new onset or worsening acute heart failure. Congestion characterized by dyspnea, edema, rales, jugular venous distention and need to increase diuretic doses is a hallmark of acute heart failure prompting hospitalization'}], 'secondaryOutcomes': [{'measure': 'Thrombolysis in myocardial infarction (TIMI) 3', 'timeFrame': 'hour 1', 'description': 'The rate of patients (percent) who achieved TIMI 3 coronary blood flow after percutaneous coronary intervention'}, {'measure': 'Change in systolic/diastolic blood pressure', 'timeFrame': 'minute 3', 'description': 'Change in systolic/diastolic blood pressure values (mmHg) before and after intracoronary verapamil/epinephrine'}, {'measure': 'ST segment resolution', 'timeFrame': 'hour 72', 'description': 'Degree of ST segment resolution on ECG (mm)'}, {'measure': 'Troponin I release', 'timeFrame': 'hour 72', 'description': 'Concentration of troponin I (ng/mL)'}, {'measure': 'LV EF', 'timeFrame': 'day 10', 'description': 'Left ventricular ejection fraction (LV EF) (percent)'}, {'measure': 'Myocardial injury', 'timeFrame': 'day 2', 'description': 'Total volume (mL) of microvascular obstruction, myocardial necrosis, edema, and hemorrhagic impregnation according to MRI data'}, {'measure': 'SPECT-based coronary reserve', 'timeFrame': 'day 7', 'description': 'Coronary reserve will be measured by cardiac single photon emission computed tomography (SPECT) with technetium-99m-labeled methoxy-isobutyl isonitrile (99mТсMIBI) at rest and during pharmacological stress-test (counts)'}, {'measure': 'Change in heart rate values', 'timeFrame': 'minute 3', 'description': 'Change in heart rate values (beat per minute) before and after intracoronary verapamil/epinephrine'}, {'measure': 'LV EDV', 'timeFrame': '10 days', 'description': 'Left ventricular end-diastolic volume (LV EDV) (mL)'}, {'measure': 'LV ESV', 'timeFrame': 'day 10', 'description': 'Left ventricular end-systolic volume (LV ESV) (mL)'}, {'measure': 'LV WMSI', 'timeFrame': 'day 10', 'description': 'Left ventricular wall motion score index (LV WMSI) (conventional units)'}, {'measure': 'Arrhythmias', 'timeFrame': 'minute 5', 'description': 'Frequency of arrhythmias (atrial fibrillation, atrial flutterу, supraventricular tachycardia, premature ventricular contractions, ventricular tachycardia, conduction disorders and other heart rhythm disorders) after intracoronary administration verapamil and/or epinephrine'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Primary PCI', 'No-reflow', 'Intracoronary epinephrine'], 'conditions': ['ST Elevation Myocardial Infarction', 'Percutaneous Coronary Intervention', 'No-Reflow Phenomenon']}, 'referencesModule': {'references': [{'pmid': '40846132', 'type': 'DERIVED', 'citation': 'Dil S, Ryabov V, Maslov L, Mochula O, Mochula A, Kercheva M, Zavadovsky K, Vyshlov E. Assessing coronary microvascular dysfunction in refractory no-reflow: Insights from dynamic myocardial perfusion scintigraphy and cardiac MRI. Microvasc Res. 2025 Nov;162:104862. doi: 10.1016/j.mvr.2025.104862. Epub 2025 Aug 20.'}]}, 'descriptionModule': {'briefSummary': 'The trial aims to estimate the efficacy and safety of the intracoronary administration of adrenalin, verapamil, as well as their combination compared to standard treatment in patients with STEMI and refractory coronary no-reflow despite conventional treatment during percutaneous coronary intervention (PPCI)', 'detailedDescription': 'Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion strategy for treating acute ST-segment elevation myocardial infarction (STEMI). The main goals are to restore epicardial infarct-related artery patency and to achieve microvascular reperfusion as early as possible. No-reflow is the term used to describe inadequate myocardial perfusion of a given coronary segment without angiographic evidence of persistent mechanical obstruction of epicardial vessels and it refers to the high resistance of microvascular blood flow encountered during opening of the infarct-related coronary artery. Despite optimal evidence-based PPCI, myocardial no-reflow can still occur, negating many of the benefits of restoring culprit vessel patency, and is associated with a worse in-hospital and long-term prognosis.\n\nAccording to clinical guidelines, nitrates, adenosine, platelet IIb / IIIa receptor inhibitors and thrombus extraction can be used to prevent and treat this complication.These methods have demonstrated the ability to improve coronary blood flow in experiment and small clinical trials, however, limiting the zone of myocardial necrosis and improving disease outcomes have not been achieved.\n\nThe search for new methods of influencing the pathogenetic links of this complication is urgent. One of the main potentially reversible factors in the pathogenesis of the no-reflow phenomenon, along with microvascular obstruction, is microvascular arteriolar spasm. Thus, this problem of emergency cardiology remains relevant and requires further research, new methods of prevention and treatment.\n\nAside from exerting beta-1 agonist properties at higher doses and increasing the inotropic and chronotropic stimulation of the myocardium, epinephrine may, at lower doses, exert potent beta receptor agonist properties that mediate coronary vasodilatation. Another drug with a pronounced coronary vasodilation effect is verapamil.\n\nBased on the pharmacodynamic effects of epinephrine and verapamil, it is expected to increase the vasodilating effect when they are used together, due to the additive type of synergistic interaction, which will improve coronary microcirculation after PCI in patients with acute myocardial infarction and refractory no-reflow phenomenon.\n\nCurrently, in clinical practice, there is a possibility of very sensitive diagnosis of microvascular obstruction (MVO) using magnetic resonance imaging (MRI), as well as the area of the coronary reserve according to dynamic perfusion scintigraphy of the myocardium. It is advisable to evaluate the effectiveness of treatment of the no-reflow phenomenon using these methods.\n\nThe trial aims to estimate the efficacy and safety of the administration of intracoronary epinephrine, verapamil, as well as their combination versus to standard treatment in patients with STEMI and refractory coronary no-reflow despite conventional treatments during PPCI.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* patients with ST-elevation myocardial infarction\n* Infarct-related artery TIMI flow grade 0-2 during the interventional procedure after the initial opening of the vessel.\n* Written the informed consent to participate in research\n\nExclusion Criteria:\n\n* Unable to undergo or contra-indications for MRI or SPECT'}, 'identificationModule': {'nctId': 'NCT04573751', 'acronym': 'EPIVER', 'briefTitle': 'The EPIVER Randomized Controlled Trial', 'organization': {'class': 'OTHER', 'fullName': 'Tomsk National Research Medical Center of the Russian Academy of Sciences'}, 'officialTitle': 'Intracoronary Administration of Epinephrine and Verapamil in the Refractory No-reflow Phenomenon in Patients With Acute Myocardial Infarction: The EPIVER Randomized Controlled Trial', 'orgStudyIdInfo': {'id': 'EPIVER'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'SHAM_COMPARATOR', 'label': 'Standard therapy', 'description': 'No intracoronary epinephrine and verapamil', 'interventionNames': ['Drug: Standard therapy']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Epinephrine', 'description': 'Intracoronary bolus epinephrine injection requires two ampoules each of 1:1,000 epinephrine (1 μg/mL) diluted into 100 mL of normal saline solution (to 20 μg/mL epinephrine solution); therefore, a 5-mL syringe contains 100 μg of epinephrine. Intracoronary epinephrine will be administered at a dose of 100 μg and at a lower dose of 80 μg in patients with blood pressure \\>160 mmHg', 'interventionNames': ['Drug: Epinephrine']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Verapamil', 'description': 'Intracoronary verapamil is administered at a dose of 0.5 mg.', 'interventionNames': ['Drug: Verapamil']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Epinephrine + verapamil', 'description': 'Intracoronary administration of epinephrine at a dose of 80-100 μg and verapamil at a dose of 0.5 mg.', 'interventionNames': ['Drug: Epinephrine + verapamil']}], 'interventions': [{'name': 'Standard therapy', 'type': 'DRUG', 'otherNames': ['Control'], 'description': 'Standard therapy as follows: adenosine, nitroglycerine, thrombus aspiration/extraction, and platelet IIb/IIIa receptor inhibitors.', 'armGroupLabels': ['Standard therapy']}, {'name': 'Epinephrine', 'type': 'DRUG', 'otherNames': ['Epi'], 'description': 'Standard therapy plus epinephrine as follows: epinephrine, adenosine, nitroglycerine, thrombus aspiration/extraction, and platelet IIb/IIIa receptor inhibitors.', 'armGroupLabels': ['Epinephrine']}, {'name': 'Verapamil', 'type': 'DRUG', 'otherNames': ['Ver'], 'description': 'Standard therapy plus verapamil as follows: verapamil, adenosine, nitroglycerine, thrombus aspiration/extraction, and platelet IIb/IIIa receptor inhibitors.', 'armGroupLabels': ['Verapamil']}, {'name': 'Epinephrine + verapamil', 'type': 'DRUG', 'otherNames': ['Epi+Ver'], 'description': 'Standard therapy plus epinephrine + verapamil as follows: epinephrine, verapamil, adenosine, nitroglycerine, thrombus aspiration/extraction, and platelet IIb/IIIa receptor inhibitors.', 'armGroupLabels': ['Epinephrine + verapamil']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Tomsk', 'state': 'Tomsk Oblast', 'country': 'Russia', 'facility': 'Cardiology Research Institute, Tomsk NRMC', 'geoPoint': {'lat': 56.50049, 'lon': 84.98216}}], 'overallOfficials': [{'name': 'Vyacheslav V Ryabov, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Cardiology Research Institute, Tomsk NRMC'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Tomsk National Research Medical Center of the Russian Academy of Sciences', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}