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

Sponsors

Lead Sponsor: Tomsk National Research Medical Center of the Russian Academy of Sciences

Source Tomsk National Research Medical Center of the Russian Academy of Sciences
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.

Overall Status Recruiting
Start Date 2020-12-30
Completion Date 2023-03-01
Primary Completion Date 2022-03-01
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Mortality month 1
New onset or worsening acute heart failure month 1
Secondary Outcome
Measure Time Frame
Thrombolysis in myocardial infarction (TIMI) 3 hour 1
Change in systolic/diastolic blood pressure minute 3
ST segment resolution hour 72
Troponin I release hour 72
LV EF day 10
Myocardial injury day 2
SPECT-based coronary reserve day 7
Change in heart rate values minute 3
LV EDV 10 days
LV ESV day 10
LV WMSI day 10
Arrhythmias minute 5
Enrollment 104
Condition
Intervention

Intervention Type: Drug

Intervention Name: Standard therapy

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

Arm Group Label: Standard therapy

Other Name: Control

Intervention Type: Drug

Intervention Name: Epinephrine

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

Arm Group Label: Epinephrine

Other Name: Epi

Intervention Type: Drug

Intervention Name: Verapamil

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

Arm Group Label: Verapamil

Other Name: Ver

Intervention Type: Drug

Intervention Name: Epinephrine + verapamil

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

Arm Group Label: Epinephrine + verapamil

Other Name: Epi+Ver

Eligibility

Criteria:

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

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Vyacheslav V Ryabov, MD, PhD Principal Investigator Cardiology Research Institute, Tomsk NRMC
Overall Contact

Last Name: Vyacheslav V. Ryabov, MD, Phd

Phone: +73822553689

Email: [email protected]

Location
Facility: Status: Contact: Cardiology Research Institute, Tomsk NRMC Stanislav V Dil +79131006366 [email protected]
Location Countries

Russian Federation

Verification Date

2021-06-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 4
Arm Group

Label: Standard therapy

Type: Sham Comparator

Description: No intracoronary epinephrine and verapamil

Label: Epinephrine

Type: Active Comparator

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

Label: Verapamil

Type: Active Comparator

Description: Intracoronary verapamil is administered at a dose of 0.5 mg.

Label: Epinephrine + verapamil

Type: Active Comparator

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

Acronym EPIVER
Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Research News