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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04514757
Recruitment Status : Recruiting
First Posted : August 17, 2020
Last Update Posted : December 22, 2021
Sponsor:
Collaborator:
University of Oklahoma
Information provided by (Responsible Party):
Jonathan K. Ho, University of California, Los Angeles

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Atrial Fibrillation Device: active tVNS Device: sham tVNS Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 266 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Transcutaneous (Tragus) Vagal Nerve Stimulation (tVNS) for Post-op Atrial Fibrillation (POAF)
Actual Study Start Date : September 20, 2021
Estimated Primary Completion Date : August 2023
Estimated Study Completion Date : September 2023

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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.

  2. 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)

  3. Sympathetic neural markers [ Time Frame: Postop day 3 (1 day) ]
    Reduction in sympathetic neural markers including norepinephrine, Neuropeptide Y (NPY), and galanin.

  4. 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.

  5. 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. 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).

  7. 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).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04514757


Contacts
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Contact: Jennifer Scovotti 310-206-4484 jscovotti@mednet.ucla.edu
Contact: Claudia Bueno 310-267-2130 cbueno@mednet.ucla.edu

Locations
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United States, California
University of California, Los Angeles Recruiting
Los Angeles, California, United States, 90095
Contact: Jennifer Scovotti    310-206-4484    JScovotti@mednet.ucla.edu   
Contact: Claudia Bueno    310-267-2130    cbueno@mednet.ucla.edu   
Principal Investigator: Jonathan Ho, MD         
Principal Investigator: Marmar Vaseghi, MD         
United States, Oklahoma
University of Oklahoma Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Stavros Stavrakis, MD, PhD    405-271-9696    stavros-stavrakis@ouhsc.edu   
Principal Investigator: Stavros Stavrakis, MD., PhD         
Sponsors and Collaborators
University of California, Los Angeles
University of Oklahoma
Investigators
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Principal Investigator: Jonathan Ho, MD University of California, Los Angeles
Principal Investigator: Marmar Vaseghi, MD University of California, Los Angeles
Principal Investigator: Stavros Stavrakis, MD, PhD University of Oklahoma
Publications:

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Responsible Party: Jonathan K. Ho, Associate Clinical Professor, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT04514757    
Other Study ID Numbers: 20-001636
First Posted: August 17, 2020    Key Record Dates
Last Update Posted: December 22, 2021
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Jonathan K. Ho, University of California, Los Angeles:
post-operative atrial fibrillation
transcutaneous (tragus) vagal nerve stimulation
outcomes
Additional relevant MeSH terms:
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Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes