Transcutaneous Vagal Nerve Stimulation to Prevent Tachyarrhythmias in Patients Early Following Myocardial Infarction (EARLY-VAGUS)

Transcutaneous Vagal Nerve Stimulation to Prevent Tachyarrhythmias in Patients Early Following Myocardial Infarction: A Randomized Clinical Trial

Among patients early following ST-segment (ST) elevation myocardial infarction, transcutaneous vagus nerve stimulation is associated with a reduce of the burden of premature ventricular contractions in the first 40 days post-myocardial infarction (MI).

The above hypothesis will be tested with a randomized, prospective, parallel, single-blind clinical trial. The expected study duration is approximately 12 months from the time the first subject is enrolled (planned for June 2023) to the time of study's termination date (December 2024). Patient enrollment is planned to take place at two major centers in Greece. The researchers will obtain approval by the institutional review board (IRB).

Study Overview

• Status: Not yet recruiting
• Conditions: Myocardial Infarction; Tachyarrhythmia
• Intervention / Treatment: Device: Parasym device (active, current (mA) < discomfort threshold); Device: Parasym device (sham, current (mA) = 0)

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Konstantinos Tsioufis, Professor; Phone Number: 2132088000; Email: ktsioufis@hippocratio.gr

Study Locations

• Greece
  • Attica
    • Athens, Attica, Greece, 11527
      • First Department of Cardiology, Hippocration General Hospital, National and Kapodistrian University of Athens
      • Sub-Investigator: Panagiotis Tsioufis, MD, MSc
      • Contact: Konstantinos Tsioufis, Professor; Phone Number: 2132088000; Email: ktsioufis@hippocratio.gr
      • Principal Investigator: Ioannis Doundoulakis, MD, MSc (Res)
      • Principal Investigator: Konstantinos Tsioufis, Professor
  • Attiki
    • Athens, Attiki, Greece, 15125
      • Athens Heart Center Amarousion
      • Principal Investigator: Dimitrios Tsiachris
• United Arab Emirates
  • Abu Dhabi, United Arab Emirates
    • Biomedical Engineering, Khalifa University of Science and Technology
    • Contact: Leontios Hadjileontiadis; Email: leontios.hadjileontiadis@ku.ac.ae
    • Sub-Investigator: Leontios Hadjileontiadis
• United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Heart Rhythm Institute, University of Oklahoma Health Sciences Center
      • Contact: Stavros Stavrakis, MD, PhD; Email: Stavros-stavrakis@ouhsc.edu
      • Sub-Investigator: Stavros Stavrakis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female patients aged ≥18 years
• ST-elevation myocardial infarction which is treated with a primary percutaneous coronary intervention
• Signed written informed consent by the patient for participation in the study and agreement to comply with the medication and the follow-up schedule

Exclusion Criteria:

A patient will be excluded from the study if one or more of all the following criteria are present:

• < 3 months after prior ablation
• Patients on amiodarone
• Patients with known thyroid issues, on renal-dialysis
• Life expectancy of < 12 months
• Complex congenital heart disease
• Cardiogenic shock
• Women who are pregnant (as evidenced by pregnancy test if pre-menopausal)
• Known channelopathy such as Brugada syndrome, long QT syndrome, or Catecholaminergic monomorphic ventricular tachycardia
• Symptomatic sinus bradycardia or sinus node dysfunction at baseline without an implantable pacemaker
• Complete heart block or trifascicular block without an implantable pacemaker
• Recurrent vasovagal syncope
• Pre-existing implantable cardioverter-defibrillator (ICD)
• Secondary prevention indication for an ICD (i.e. sustained ventricular arrhythmias occurring more than 48 hours after qualifying myocardial infarction (patients with ventricular arrhythmias occurring ≤48 hours of myocardial infarction, or with non-sustained ventricular tachycardia at any time, are not excluded))
• On the heart transplant list
• Recurrent unstable angina despite revascularisation (defined as ongoing chest pain or ischemic symptoms at rest or with minimal exertion despite adequate treatment with anti-anginal medications)
• Congestive heart failure New York Heart Association class IV, defined as shortness of breath at rest, which is refractory to medical treatment (not responding to treatment)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active Transcutaneous Vagal Nerve Stimulation	Device: Parasym device (active, current (mA) < discomfort threshold); Active transcutaneous Vagal Nerve Stimulation (tVNS) (Parasym device, Parasym Health, Inc, London, UK) will be performed with a clip attached to the ear at 20 hertz (Hz), 250 microseconds (ms) at a current just below discomfort threshold for 30 minutes twice a day, starting on post-MI day 0. Stimulation will continue until 7 days post-MI or discharge.
Sham Comparator: Sham Transcutaneous Vagal Nerve Stimulation	Device: Parasym device (sham, current (mA) = 0); Parasym device will be attached to the ear twice a day, turned on but current set to 0 milliamp (mA), starting on post-MI day 0. Stimulation will continue until 7 days post-MI or discharge.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Ventricular tachycardia burden	Patients will undergo noninvasive continuous ECG monitoring using a 24-hour Holter monitoring at 1, 7 and 40 days to evaluate their number of Premature ventricular contractions (PVCs) and number of Non-Sustain Ventricular Tachycardias (NSVT).	1, 7 and 40 days follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Heart Rate Variability	Patients will undergo noninvasive continuous ECG monitoring using a 24-hour Holter monitoring at 1, 7 and 40 days to evaluate Heart Rate Variability	1, 7 and 40 days follow-up
Change of Heart Rate Turbulence	Patients will undergo noninvasive continuous ECG monitoring using a 24-hour Holter monitoring at 1, 7 and 40 days to evaluate Heart Rate Turbulence	1, 7 and 40 days follow-up
Change of Deceleration Capacity (DC)	Patients will undergo noninvasive continuous ECG monitoring using a 24-hour Holter monitoring at 1, 7 and 40 days to evaluate Deceleration Capacity	1, 7 and 40 days follow-up
Change of Echocardiographic strain	Patients will undergo echocardiography at 1, 7 and 40 days to assess Myocardial substrate lesions and Post-infraction fibrosis	1, 7 and 40 days follow-up
Change of Left Ventricle Ejection Fraction (LVEF)	Patients will undergo echocardiography at 1, 7 and 40 days to assess Left Ventricle Ejection Fraction	1, 7 and 40 days follow-up
Change of Signal Averaged ECG	Patients will undergo a 12-lead electrocardiogram at 1, 7 and 40 days	1, 7 and 40 days follow-up
Change of T Wave alternans and equal indexes derived from holter monitoring	Patients will undergo noninvasive continuous ECG monitoring using a 24-hour Holter monitoring at 1, 7 and 40 days	1, 7 and 40 days follow-up
Change of QT duration	Patients will undergo noninvasive continuous ECG monitoring using a 24-hour Holter monitoring at 1, 7 and 40 days	1, 7 and 40 days follow-up
Pain assessment	Pain scores will be assessed on postoperative days 0-7 using the visual analog score (Scale 0-10). Zero for no pain and ten being the worst pain experienced. They will be obtained and recorded into the medical record by the nurse monitoring the subject as part of standard care	7 days follow-up
Number of participants with adverse effects	Number of participants with pruritus, flush, pain at the stimulation site	7 days follow-up

Collaborators and Investigators

• Sponsor: Hippocration General Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2023
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: January 30, 2023
• First Submitted That Met QC Criteria: February 20, 2023
• First Posted (Actual): March 1, 2023

Study Record Updates

• Last Update Posted (Actual): March 1, 2023
• Last Update Submitted That Met QC Criteria: February 20, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: transcutaneous vagal nerve stimulation
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Myocardial Infarction; Infarction; Tachycardia
• Other Study ID Numbers: EARLY-VAGUS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes