Auricular Vagus Stimulation and STEMI

• ClinicalTrials.gov Identifier: NCT05992259
• Recruitment Status: Recruiting
• First Posted: August 15, 2023
• Last Update Posted: August 15, 2023
• Sponsor: Bakulev Scientific Center of Cardiovascular Surgery
• Collaborator: State Budget Public Health Institution Scientific Research Institute - Ochapovsky Regional Clinical Hospital
• Information provided by (Responsible Party): Vladimir A Shvartz, MD, Bakulev Scientific Center of Cardiovascular Surgery

Study Description

Brief Summary:

At the moment, the invasive strategy for the infarct-associated coronary artery in patients with ST-segment elevation myocardial infarction (STEMI) necessary to save the myocardium and reduce the size of the necrosis zone remains the leading one. However, despite the high efficiency of providing medical care to patients with acute coronary syndrome (ACS), there remains a high mortality and disability of this group of patients. In this regard, the search for new drug and non-drug strategies for the treatment of patients with ACS is actively continuing. Over the past decade, it has been shown that transcutaneous vagus nerve stimulation (TENS) has a cardioprotective effect both in chronic heart failure and in coronary heart disease, improves cardiac function, prevents reperfusion injury, weakens myocardial remodeling, increases the effectiveness of defibrillation and reduces the size of a heart attack. One of the methods of noninvasive stimulation of the afferent fibers of the vagus nerve is percutaneous electrical stimulation of the auricular branch of the vagus nerve. However, further studies are needed to determine whether stimulation of the tragus can improve the long-term clinical outcome in this cohort of patients.

Condition or disease	Intervention/treatment	Phase
Vagus Nerve Stimulation; Acute Coronary Syndrome; Ischemia Reperfusion Injury	Device: TENS	Not Applicable

Detailed Description:

ACS is a combined concept for such life-threatening conditions as acute myocardial infarction (AMI) and unstable angina, which are exacerbations of coronary heart disease. However, despite the high effectiveness of the invasive treatment strategy, there remains a high mortality and disability of this group of patients. One of the reasons for this problem is reperfusion injury of the myocardium during revascularization, since reperfusion itself causes myocardial damage, known as Myocardial Ischemia Reperfusion Injury (MIRI). Every year, new data from experimental studies and small clinical trials appear, confirming the concept that MIRI makes a big contribution to the final size of a heart attack and cardiac myocardial function. Currently, there is no specific treatment aimed at MIRI in patients with STEMI. Thus, new treatment methods are needed that can reduce MIRI in revascularized patients. In the course of small clinical studies, it was shown that against the background of vagus nerve stimulation, a significant decrease in heart rate occurs, inflammatory processes and cellular apoptosis are suppressed, left ventricular remodeling decreases and myocardial contractile function improves. Also, a significant decrease in MIRI is demonstrated with percutaneous stimulation of the vagus nerve in the acute period of myocardial infarction. The data of the first clinical trial with VNS in patients with STEMI were published in 2017 (doi:10.1016/j.jcin.2017.04.036). This experimental study increases the likelihood that this noninvasive therapy can be used to treat patients with STEMI who are undergoing primary percutaneous coronary intervention (PCI). New studies are needed to prove the safety and effectiveness of vagus nerve stimulation in patients with STEMI.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: 1:1 randomization of active stimulation vs. sham stimulation
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Auricular Vagus Stimulation and ST-Segment Elevation Myocardial Infarction
• Actual Study Start Date: September 1, 2022
• Estimated Primary Completion Date: September 30, 2024
• Estimated Study Completion Date: December 1, 2025

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Active TENS; It will be performed attached to the tragus of the left ear.	Device: TENS; TENS will be performed from the moment of admission to the PCI, during the PCI and for the next 30 minutes after it.
Sham Comparator: Sham TENS; It will be performed attached to the earlobe of the left ear.	Device: TENS; TENS will be performed from the moment of admission to the PCI, during the PCI and for the next 30 minutes after it.

Outcome Measures

Primary Outcome Measures :

1. Hospital mortality [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 14 days. ]
   The number of patients who died in the hospital.
2. 30-day mortality [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 30 days. ]
   The number of patients who died within 30 days from the development of myocardial infarction.

Secondary Outcome Measures :

1. Number of participants with non-lethal events. [ Time Frame: From the date of randomization to the date of any of the listed events, assessed up to 14 days. ]
   The main hospital non-lethal events (Pulmonary edema, Cardiogenic shock, Cardiac arrhythmias: Atrial fibrillation, Ventricular tachycardia/fibrillation, Accelerated idioventricular rhythm/Atrioventricular block II, III).

Other Outcome Measures:

1. Assessment of the level of myocardial damage. [ Time Frame: Diagnosis will be carried out during hospitalization, after 6 hours and on the 4th day of hospitalization. ]
   Dynamics of Troponin I (hs-cTnI) in blood plasma.
2. Assessment of the level of inflammation. [ Time Frame: Diagnosis will be carried out during hospitalization and after 24 hours. ]
   Dynamics of high-sensitivity C-reactive protein (hs-CRP) in blood plasma. Dynamics of copeptin (CPP) in blood plasma.
3. Assessment of the level of heart failure [ Time Frame: Diagnosis will be carried out during hospitalization and on the 4th day of hospitalization. ]
   Dynamics of NT-proBNP in blood plasma.

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• patients with STEMI who have signed an informed voluntary consent to participate in the study;
• primary myocardial infarction;
• treatment in the first 12 hours from the onset of pain syndrome;
• primary PCI.

Exclusion Criteria:

• acute heart failure III-IV;
• bradyarrhythmias;
• atrial fibrillation/flutter at the time of switching on;
• Thrombolytic therapy at the prehospital stage;
• a history of myocardial infarction;
• PCI/coronary artery bypass grafting (CABG) in the anamnesis.

Contacts and Locations

Contacts

Contact: Vladimir Shvartz, MD, DM; +79032619292; vashvarts@bakulev.ru

Locations

Russian Federation

Scientific Research Institute Ochapovsky Regional Clinical Hospital; Recruiting

Krasnodar, Russian Federation

Contact: Sofia Kruchinova, MD, PhD +79189504597 skruchinova@mail.ru

Sponsors and Collaborators

Bakulev Scientific Center of Cardiovascular Surgery

State Budget Public Health Institution Scientific Research Institute - Ochapovsky Regional Clinical Hospital

Investigators

• Principal Investigator: Vladimir Shvartz, MD, DM; Bakoulev Scientific Center for Cardiovascular Surgery

More Information

Additional Information:

Low-Level Tragus Stimulation for the Treatment of Ischemia and Reperfusion Injury in Patients With ST-Segment Elevation Myocardial Infarction: A Proof-of-Concept Study 

Vagal Cardioprotection in Reperfused Acute Myocardial Infarction 

• Responsible Party: Vladimir A Shvartz, MD, MD, DM, Professor, Bakulev Scientific Center of Cardiovascular Surgery
• ClinicalTrials.gov Identifier: NCT05992259
• Other Study ID Numbers: #12
• First Posted: August 15, 2023
• Last Update Posted: August 15, 2023
• Last Verified: August 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Vladimir A Shvartz, MD, Bakulev Scientific Center of Cardiovascular Surgery:

auricular stimulation; auricular vagus nerve stimulation; transcutaneous vagus nerve stimulation (TENS); vagus nerve stimulation (VNS); acute coronary syndrome; myocardial ischemia reperfusion injury; ST-segment elevation myocardial infarction; coronary heart disease; acute myocardial infarction; mortality; atrial fibrillation

Additional relevant MeSH terms:

Myocardial Infarction; Acute Coronary Syndrome; Reperfusion Injury; ST Elevation Myocardial Infarction; Ischemia; Pathologic Processes; Infarction; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications