The EPIVER Randomized Controlled Trial

NCT ID: NCT04573751

Last Updated: 2024-04-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

104 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-30

Study Completion Date

2024-01-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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)

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

According 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.

The 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.

Aside 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.

Based 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.

Currently, 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.

The 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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

ST Elevation Myocardial Infarction Percutaneous Coronary Intervention No-Reflow Phenomenon

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Standard therapy

No intracoronary epinephrine and verapamil

Group Type SHAM_COMPARATOR

Standard therapy

Intervention Type DRUG

Standard therapy as follows: adenosine, nitroglycerine, thrombus aspiration/extraction, and platelet IIb/IIIa receptor inhibitors.

Epinephrine

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

Group Type ACTIVE_COMPARATOR

Epinephrine

Intervention Type DRUG

Standard therapy plus epinephrine as follows: epinephrine, adenosine, nitroglycerine, thrombus aspiration/extraction, and platelet IIb/IIIa receptor inhibitors.

Verapamil

Intracoronary verapamil is administered at a dose of 0.5 mg.

Group Type ACTIVE_COMPARATOR

Verapamil

Intervention Type DRUG

Standard therapy plus verapamil as follows: verapamil, adenosine, nitroglycerine, thrombus aspiration/extraction, and platelet IIb/IIIa receptor inhibitors.

Epinephrine + verapamil

Intracoronary administration of epinephrine at a dose of 80-100 μg and verapamil at a dose of 0.5 mg.

Group Type ACTIVE_COMPARATOR

Epinephrine + verapamil

Intervention Type DRUG

Standard therapy plus epinephrine + verapamil as follows: epinephrine, verapamil, adenosine, nitroglycerine, thrombus aspiration/extraction, and platelet IIb/IIIa receptor inhibitors.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Standard therapy

Standard therapy as follows: adenosine, nitroglycerine, thrombus aspiration/extraction, and platelet IIb/IIIa receptor inhibitors.

Intervention Type DRUG

Epinephrine

Standard therapy plus epinephrine as follows: epinephrine, adenosine, nitroglycerine, thrombus aspiration/extraction, and platelet IIb/IIIa receptor inhibitors.

Intervention Type DRUG

Verapamil

Standard therapy plus verapamil as follows: verapamil, adenosine, nitroglycerine, thrombus aspiration/extraction, and platelet IIb/IIIa receptor inhibitors.

Intervention Type DRUG

Epinephrine + verapamil

Standard therapy plus epinephrine + verapamil as follows: epinephrine, verapamil, adenosine, nitroglycerine, thrombus aspiration/extraction, and platelet IIb/IIIa receptor inhibitors.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Control Epi Ver Epi+Ver

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* patients with ST-elevation myocardial infarction
* Infarct-related artery TIMI flow grade 0-2 during the interventional procedure after the initial opening of the vessel.
* Written the informed consent to participate in research

Exclusion Criteria

* Unable to undergo or contra-indications for MRI or SPECT
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Tomsk National Research Medical Center of the Russian Academy of Sciences

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Vyacheslav V Ryabov, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Cardiology Research Institute, Tomsk NRMC

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Cardiology Research Institute, Tomsk NRMC

Tomsk, Tomsk Oblast, Russia

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Russia

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 40846132 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

EPIVER

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.