Transcutaneous (Tragus) Vagal Nerve Stimulation for Post-op Afib (STOP_AF)

October 12, 2023 updated by: Jonathan K. Ho, University of California, Los Angeles

Transcutaneous (Tragus) Vagal Nerve Stimulation (tVNS) for Post-op Atrial Fibrillation (POAF)

Patients undergoing cardiac surgery are at high risk of developing atrial fibrillation (AF), with estimated rates of 30-50% and occurs at approximately 2-4 days after surgery. The autonomic nervous system is known to play a key role in AF. Animal studies have indicated that duration and inducibility of AF can be decreased with intermittent vagus nerve stimulation (VNS). In humans, literature suggests that transcutaneous (tragus) VNS (tVNS) can serve as a potentially non-invasive therapy for treatment of post-operative AF (POAF) by reducing inflammation and increasing atrial refractory period. The purpose of this study is to determine the value of tVNS in reducing the burden of POAF and days of hospitalization after cardiac surgery.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The trial will have two study arms: active tVNS vs. sham tVNS. Patients will be randomized to active tVNS vs. sham tVNS and will receive optimal post-op care in both arms. Active 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 one hour twice a day, starting on post-day 0. For sham tVNS, Parasym device will be attached to the ear twice a day, turned on but current set to 0 milliamp (mA), starting on post-op day 0. Stimulation will continue until 5 days post-op or discharge. Discomfort threshold will be determined in both arms pre-operatively in the conscious state. This current will be used for stimulation for this patient until they are awake and extubated after surgery. The stimulation threshold may be reassessed once the patient is able to provide feedback.

Patients will be approached and recruited prior to their scheduled cardiac surgery. Recruited patients who give informed consent will have the discomfort stimulation threshold (current that leads to discomfort at the tragus) determined prior to surgery. Post-operatively, stimulation will be performed in the tVNS group at just below discomfort threshold. In the sham group, the stimulator will be turned on but current set at 0 mA. Stimulations will be performed within 12 hours of arrival to the ICU after surgery, and then twice a day between the hours of 7:00-9:00 am and 6:00-8:00 pm. If POAF develops in either arm, stimulation will be continued for the full 5 days. Ten ml of blood will be drawn within 12 hours of arrival to the ICU after surgery and on day 3 post-op for measurement of biomarkers. Serum will be stored at -80 Celsius and processed in batches of 10-15 samples.

Sample Size:

The investigators expect cardiac surgery to be associated with 40% incidence of POAF. The investigators expect tVNS to reduce this incidence by 40%. A sample size of 133 subjects per arm will be able to achieve 80% power at alpha of 0.05. If interim analysis is planned, Pocock method will be used and a p value of 0.03 will be used for interim and 0.03 for final analysis. Data will be analyzed according to the intention-to-treat principle.

Randomization:

A 1:1 randomization ratio for the tVNS vs. sham will be utilized. Patients who meet all of the inclusion and none of the exclusion criteria will be randomized in the order of their enrollment. After completing the Informed Consent process, the subject is then randomized following completion of the baseline and demographics information case report forms. Randomization should occur prior to any study-related tests or procedures. The subjects will be considered enrolled in the study once randomization has occurred.

Randomization will be stratified by clinical center and post-operative amiodarone use. A computer-generated randomization list with random permuted block of a variable will be produced for each clinical center. Investigators and other study staff members should not be able to identify the study assignment until this time. If a randomization assignment is inadvertently disclosed prior to use, the assignment will never be used.

A report of randomization compliance will be generated at the conclusion of the study.

Study Type

Interventional

Enrollment (Estimated)

266

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095
        • Recruiting
        • University of California, Los Angeles
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jonathan Ho, MD
        • Principal Investigator:
          • Marmar Vaseghi, MD
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • University of Oklahoma
        • Contact:
        • Principal Investigator:
          • Stavros Stavrakis, MD., PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Patients scheduled to undergo coronary artery bypass surgery, major vascular/aneurysm repair requiring bypass, valvular replacement or repair, or both, for clinically indicated reasons.
  2. Age ≥ 18 years.
  3. Sinus rhythm at baseline.
  4. Provision of signed informed consent and stated willingness to comply with all study procedures for duration of the study

Exclusion Criteria:

  1. Emergent surgery
  2. Anticipated amiodarone use
  3. Patients with permanent or persistent atrial fibrillation
  4. Planned concomitant atrial Maze procedure
  5. Complex congenital heart disease
  6. Women who are pregnant (as evidenced by pregnancy test if pre-menopausal).
  7. Left ventricular assist device or status post orthotopic heart or lung transplantation
  8. Unable or unwilling to comply with protocol requirements.
  9. Known channelopathy such as Brugada syndrome, long QT syndrome, or Catecholaminergic monomorphic ventricular tachycardia
  10. Symptomatic sinus bradycardia or sinus node dysfunction at baseline without an implantable pacemaker.
  11. Complete heart block or trifascicular block without an implantable pacemaker
  12. Recurrent vasovagal syncope
  13. Unilateral or bilateral vagotomy
  14. Chronic amiodarone use

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention Group
Active tVNS (Parasym device, Parasym Health, Inc, London, UK) will be performed with a clip attached to ear at 20 Hz, 250ms at a current just below discomfort threshold for one hour twice a day, starting on post-day 0. Stimulation will continue until 5 days post-operatively or discharge.
Device: active tVNS
20 Hz, 250ms at a current just below discomfort threshold for one hour twice a day, starting on post-day 0. Stimulation will continue until 5 days post-operatively or discharge.
Sham Comparator: Control Group
Sham tVNS will be performed by attaching the Parasym device to the ear and setting output to 0. Stimulation will continue until 5 days post-operatively or discharge.
Device: sham tVNS
Current set a 0 mA, starting on post-op day 0. Stimulation will continue until 5 days post-operatively or discharge.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Atrial Fibrillation
Time Frame: 6 days
Incidence of post-operative atrial fibrillation for postoperative day 0-5 (postop day 0 is the day of the surgery and is the first day of the time frame and postoperative day 5 is the 6th day).
6 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Days of hospitalization
Time Frame: Postop day 0 until discharge from the hospital, an average of 1 week.
Number of days in the hospital from postoperative day 0 to discharge.
Postop day 0 until discharge from the hospital, an average of 1 week.
Inflammatory markers
Time Frame: Within 12 hours of arrival to the ICU after surgery and on postop day 3 (2 days)
Reduction in inflammatory markers including C-reactive protein (CRP), Interleukin 10 (IL-10), Tumour Necrosis Factor alpha (TNF-alpha), Interleukin 6 (IL-6), and Interleukin 1 beta (IL-1β)
Within 12 hours of arrival to the ICU after surgery and on postop day 3 (2 days)
Sympathetic neural markers
Time Frame: Postop day 3 (1 day)
Reduction in sympathetic neural markers including norepinephrine, Neuropeptide Y (NPY), and galanin.
Postop day 3 (1 day)
Pain assessment
Time Frame: 6 days
Pain scores will be assessed on postoperative days 0-5 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. Postop day 0 is the day of the surgery and is the first day of the time frame and postoperative day 5 is the 6th day.
6 days
Narcotic Usage
Time Frame: 6 days
Total narcotic consumption will be calculated each day for postoperative days 0-5. Narcotic amount will be converted to a standard unit equivalent for comparison. Postop day 0 is the day of the surgery and is the first day of the time frame and postoperative day 5 is the 6th day.
6 days
Duration of post-op atrial fibrillation
Time Frame: 6 days
How many hours or days for each incidence of postoperative atrial fibrillation for postoperative days 0-5 (postop day 0 is the day of the surgery and is the first day of the time frame and postoperative day 5 is the 6th day).
6 days
Heart rate during atrial fibrillation
Time Frame: 6 days
The heart rate during each incidence of postoperative atrial fibrillation for postop days 0-5 (postop day 0 is the day of the surgery and is the first day of the time frame and postoperative day 5 is the 6th day).
6 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, Los Angeles

Collaborators

University of Oklahoma

Investigators

  • Principal Investigator: Stavros Stavrakis, MD, PhD, University of Oklahoma
  • Principal Investigator: Jonathan Ho, MD, University of California, Los Angeles
  • Principal Investigator: Marmar Vaseghi, MD, University of California, Los Angeles

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 20, 2021

Primary Completion (Estimated)

August 1, 2024

Study Completion (Estimated)

September 1, 2024

Study Registration Dates

First Submitted

July 29, 2020

First Submitted That Met QC Criteria

August 12, 2020

First Posted (Actual)

August 17, 2020

Study Record Updates

Last Update Posted (Actual)

October 16, 2023

Last Update Submitted That Met QC Criteria

October 12, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20-001636

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

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 register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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