ST Elevation Myocardial InfarctionEPIVERNCT04573751
The EPIVER Randomized Controlled Trial
A study testing Standard therapy, Epinephrine and Verapamil in people with ST Elevation Myocardial Infarction and Percutaneous Coronary Intervention, run by Tomsk National Research Medical Center of the Russian Academy of Sciences at 1 site in Russia.
Trial 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) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ST Elevation Myocardial Infarction, Percutaneous Coronary Intervention, No-Reflow Phenomenon
- What is being tested?
- Standard therapy, Epinephrine and Verapamil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 104 participants
- Where
- 1 siteRussia
- Study dates
- 30 Dec 2020to 31 Jan 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Unable to undergo or contra-indications for MRI or SPECT
Trial locations and contacts
1 site in 1 country.
About this study
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
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)
Read the 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.
- Conditions
- ST Elevation Myocardial Infarction, Percutaneous Coronary Intervention, No-Reflow Phenomenon
- Being tested
- Standard therapy, Epinephrine, Verapamil, Epinephrine + verapamil
- Keywords
- Primary PCI, No-reflow, Intracoronary epinephrine
- Medical subject headings
- ST Elevation Myocardial Infarction, No-Reflow Phenomenon
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard therapyDrug
Also called Control
Standard therapy as follows: adenosine, nitroglycerine, thrombus aspiration/extraction, and platelet IIb/IIIa receptor inhibitors.
EpinephrineDrug
Also called Epi
Standard therapy plus epinephrine as follows: epinephrine, adenosine, nitroglycerine, thrombus aspiration/extraction, and platelet IIb/IIIa receptor inhibitors.
VerapamilDrug
Also called Ver
Standard therapy plus verapamil as follows: verapamil, adenosine, nitroglycerine, thrombus aspiration/extraction, and platelet IIb/IIIa receptor inhibitors.
Epinephrine + verapamilDrug
Also called Epi+Ver
Standard therapy plus epinephrine + verapamil as follows: epinephrine, verapamil, adenosine, nitroglycerine, thrombus aspiration/extraction, and platelet IIb/IIIa receptor inhibitors.
| Study group | Role | What they receive |
|---|---|---|
| Standard therapy | Sham comparator | No intracoronary epinephrine and verapamil Receives: Drug: Standard therapy |
| Epinephrine | Active comparator | 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 Receives: Drug: Epinephrine |
| Verapamil | Active comparator | Intracoronary verapamil is administered at a dose of 0.5 mg. Receives: Drug: Verapamil |
| Epinephrine + verapamil | Active comparator | Intracoronary administration of epinephrine at a dose of 80-100 μg and verapamil at a dose of 0.5 mg. Receives: Drug: Epinephrine + verapamil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality
Mortality rate (percent)
Measured: month 1
New onset or worsening acute heart failure
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
Measured: month 1
Secondary outcomes (12)
Thrombolysis in myocardial infarction (TIMI) 3
The rate of patients (percent) who achieved TIMI 3 coronary blood flow after percutaneous coronary intervention
Measured: hour 1
Change in systolic/diastolic blood pressure
Change in systolic/diastolic blood pressure values (mmHg) before and after intracoronary verapamil/epinephrine
Measured: minute 3
ST segment resolution
Degree of ST segment resolution on ECG (mm)
Measured: hour 72
Troponin I release
Concentration of troponin I (ng/mL)
Measured: hour 72
LV EF
Left ventricular ejection fraction (LV EF) (percent)
Measured: day 10
Myocardial injury
Total volume (mL) of microvascular obstruction, myocardial necrosis, edema, and hemorrhagic impregnation according to MRI data
Measured: day 2
SPECT-based coronary reserve
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)
Measured: day 7
Change in heart rate values
Change in heart rate values (beat per minute) before and after intracoronary verapamil/epinephrine
Measured: minute 3
LV EDV
Left ventricular end-diastolic volume (LV EDV) (mL)
Measured: 10 days
LV ESV
Left ventricular end-systolic volume (LV ESV) (mL)
Measured: day 10
LV WMSI
Left ventricular wall motion score index (LV WMSI) (conventional units)
Measured: day 10
Arrhythmias
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
Measured: minute 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2020
- Study start30 Dec 2020
- Primary completion31 Jan 2023
- Study completion31 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ST Elevation Myocardial InfarctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 104 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tomsk National Research Medical Center of the Russian Academy of Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vyacheslav V Ryabov, MD, PhD, Principal investigator, Cardiology Research Institute, Tomsk NRMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04573751
- Sponsor's protocol ID
- CRI-203
- Acronym
- EPIVER
- Status last verified
- Jun 2026
- First submitted
- 28 Sep 2020
- Last updated
- 24 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40846132
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04573751
- Acronym / sponsor ID
- EPIVER / CRI-203
- Conditions
- ST Elevation Myocardial Infarction, Percutaneous Coronary Intervention, No-Reflow Phenomenon
- Keywords
- Primary PCI, No-reflow, Intracoronary epinephrine
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 104 participants (actual)
- Lead sponsor
- Tomsk National Research Medical Center of the Russian Academy of SciencesUniversity, hospital or other
- Study start
- 30 Dec 2020 (actual)
- Primary completion
- 31 Jan 2023 (actual)
- Study completion
- 31 Jan 2024 (actual)
- First posted
- 5 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Standard therapy | Sham comparator | Drug: Standard therapyNo intracoronary epinephrine and verapamil |
| Epinephrine | Active comparator | Drug: EpinephrineIntracoronary 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 |
| Verapamil | Active comparator | Drug: VerapamilIntracoronary verapamil is administered at a dose of 0.5 mg. |
| Epinephrine + verapamil | Active comparator | Drug: Epinephrine + verapamilIntracoronary administration of epinephrine at a dose of 80-100 μg and verapamil at a dose of 0.5 mg. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (1 listed)
- Unable to undergo or contra-indications for MRI or SPECT
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard therapyAlso: ControlStandard therapy as follows: adenosine, nitroglycerine, thrombus aspiration/extraction, and platelet IIb/IIIa receptor inhibitors. | Drug | Standard therapy |
| EpinephrineAlso: EpiStandard therapy plus epinephrine as follows: epinephrine, adenosine, nitroglycerine, thrombus aspiration/extraction, and platelet IIb/IIIa receptor inhibitors. | Drug | Epinephrine |
| VerapamilAlso: VerStandard therapy plus verapamil as follows: verapamil, adenosine, nitroglycerine, thrombus aspiration/extraction, and platelet IIb/IIIa receptor inhibitors. | Drug | Verapamil |
| Epinephrine + verapamilAlso: Epi+VerStandard therapy plus epinephrine + verapamil as follows: epinephrine, verapamil, adenosine, nitroglycerine, thrombus aspiration/extraction, and platelet IIb/IIIa receptor inhibitors. | Drug | Epinephrine + verapamil |
Primary outcome
Mortality
Time frame: month 1
Mortality rate (percent)
New onset or worsening acute heart failure
Time frame: month 1
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
12 secondary outcomes
Thrombolysis in myocardial infarction (TIMI) 3
Time frame: hour 1
Change in systolic/diastolic blood pressure
Time frame: minute 3
ST segment resolution
Time frame: hour 72
Troponin I release
Time frame: hour 72
LV EF
Time frame: day 10
Myocardial injury
Time frame: day 2
SPECT-based coronary reserve
Time frame: day 7
Change in heart rate values
Time frame: minute 3
LV EDV
Time frame: 10 days
LV ESV
Time frame: day 10
LV WMSI
Time frame: day 10
Arrhythmias
Time frame: minute 5
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2026.
- Derived from this study: PubMed 40846132Dil 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vyacheslav V Ryabov, MD, PhD principal investigator
Cardiology Research Institute, Tomsk NRMC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Standard therapy, Epinephrine and Verapamil in people with ST Elevation Myocardial Infarction and Percutaneous Coronary Intervention, run by Tomsk National Research Medical Center of the Russian Academy of Sciences at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mortality (time frame: month 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04573751, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2026.