Clinical trial NCT04573751: The EPIVER Randomized Controlled Trial
Official title: Intracoronary Administration of Epinephrine and Verapamil in the Refractory No-reflow Phenomenon in Patients With Acute Myocardial Infarction: The EPIVER Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: ST Elevation Myocardial Infarction
Percutaneous Coronary Intervention
No-Reflow Phenomenon
Keywords: Primary PCI
No-reflow
Intracoronary epinephrine
Lead sponsor: Tomsk National Research Medical Center of the Russian Academy of Sciences
Sponsor class: OTHER
First posted: 2020-10-05
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Mortality
timeFrame: month 1
measure: New onset or worsening acute heart failure
timeFrame: month 1
Secondary outcomes:
measure: Thrombolysis in myocardial infarction (TIMI) 3
timeFrame: hour 1
measure: Change in systolic/diastolic blood pressure
timeFrame: minute 3
measure: ST segment resolution
timeFrame: hour 72
measure: Troponin I release
timeFrame: hour 72
measure: LV EF
timeFrame: day 10
measure: Myocardial injury
timeFrame: day 2
measure: SPECT-based coronary reserve
timeFrame: day 7
measure: Change in heart rate values
timeFrame: minute 3
measure: LV EDV
timeFrame: 10 days
measure: LV ESV
timeFrame: day 10
measure: LV WMSI
timeFrame: day 10
measure: Arrhythmias
timeFrame: minute 5
Other outcomes:
Locations:
city: Tomsk
country: Russian Federation
facility: Cardiology Research Institute, Tomsk NRMC
state: Tomsk Region
Study officials:
affiliation: Cardiology Research Institute, Tomsk NRMC
name: Vyacheslav V Ryabov, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: