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The EPIVER Randomized Controlled Trial

Intracoronary Administration of Epinephrine and Verapamil in the Refractory No-reflow Phenomenon in Patients With Acute Myocardial Infarction: The EPIVER Randomized Controlled Trial

Status
Completed
Phases
Unknown
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT04573751
Acronym
EPIVER
Enrollment
104
Registered
2020-10-05
Start date
2020-12-30
Completion date
2024-01-31
Last updated
2026-06-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

No-Reflow Phenomenon, Percutaneous Coronary Intervention, ST Elevation Myocardial Infarction

Keywords

Primary PCI, No-reflow, Intracoronary epinephrine

Brief summary

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

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.

Interventions

DRUGStandard therapy

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

DRUGEpinephrine

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

DRUGVerapamil

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

DRUGEpinephrine + verapamil

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

Sponsors

Tomsk National Research Medical Center of the Russian Academy of Sciences
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Mortalitymonth 1Mortality rate (percent)
New onset or worsening acute heart failuremonth 1The 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

Secondary

MeasureTime frameDescription
Thrombolysis in myocardial infarction (TIMI) 3hour 1The rate of patients (percent) who achieved TIMI 3 coronary blood flow after percutaneous coronary intervention
Change in systolic/diastolic blood pressureminute 3Change in systolic/diastolic blood pressure values (mmHg) before and after intracoronary verapamil/epinephrine
ST segment resolutionhour 72Degree of ST segment resolution on ECG (mm)
Troponin I releasehour 72Concentration of troponin I (ng/mL)
LV EFday 10Left ventricular ejection fraction (LV EF) (percent)
Myocardial injuryday 2Total volume (mL) of microvascular obstruction, myocardial necrosis, edema, and hemorrhagic impregnation according to MRI data
SPECT-based coronary reserveday 7Coronary 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)
Change in heart rate valuesminute 3Change in heart rate values (beat per minute) before and after intracoronary verapamil/epinephrine
LV EDV10 daysLeft ventricular end-diastolic volume (LV EDV) (mL)
LV ESVday 10Left ventricular end-systolic volume (LV ESV) (mL)
LV WMSIday 10Left ventricular wall motion score index (LV WMSI) (conventional units)
Arrhythmiasminute 5Frequency 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

Countries

Russia

Contacts

PRINCIPAL_INVESTIGATORVyacheslav V Ryabov, MD, PhD

Cardiology Research Institute, Tomsk NRMC

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Jun 25, 2026