Transcutaneous Autonomic Modulation in Thoracic Surgery (TON-POINTS)

Transcutaneous Autonomic Modulation to Prevent Organ Injury After Thoracic Surgery

In this study, the investigators aim to determine whether non-invasive autonomic modulation decreases inflammation and complications after thoracic surgery. The investigators will test the hypothesis that low-level transcutaneous vagal nerve stimulation (LLVNS) during major thoracic surgery reduces inflammation and complications, particularly postoperative atrial fibrillation (POAF). This will be a prospective randomized pilot trial of 200 patients undergoing major thoracic surgery including lobectomy, bilobectomy, or pneumonectomy via either video-assisted thoracoscopic (VAT) or open thoracotomy. Patients will be randomized to receive ether a) LLVNS (n=100) or b) sham LLVNS (n=100) during their procedure. All patients will receive standardized anesthetic, surgical, and post-surgical care. The primary outcome in this study will be time to occurrence of in-hospital POAF, which will be compared between groups using Cox proportional hazards models. Secondary outcomes will be ICU and hospital length of stay, postoperative morbidity, postoperative mortality, and serologic markers of inflammation.

Study Overview

• Status: Terminated
• Conditions: Inflammation; Postoperative Complications; Atrial Fibrillation, Postoperative
• Intervention / Treatment: Device: Transcutaneous Low-Level Vagal Nerve Stimulation (LLVNS); Device: Sham LLVNS

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Major thoracic surgery (lobectomy, bilobectomy, or pneumonectomy via either video-assisted thoracoscopic (VAT) or open thoracotomy)

Exclusion Criteria:

• Patients >90 or <40 years of age
• Chronic atrial fibrillation
• Prior splenectomy
• Preoperative inotropic support
• Hepatic or renal failure
• Currently receiving vagal nerve stimulation therapy
• Taking centrally-acting cholinergic medications (tacrine, donepezil, rivastigmine)
• High-grade atrioventricular block (>2nd degree atrioventricular blockade)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Transcutaneous low-level vagal nerve stimulation (LLVNS); n=100 patients will be randomized to transcutaneous low-level vagal nerve stimulation (LLVNS), via a clip applied to the ear. Stimulation will be delivered throughout the procedure.	Device: Transcutaneous Low-Level Vagal Nerve Stimulation (LLVNS); Low-level vagal nerve stimulation will be delivered via a clip applied to the ear throughout the surgical procedure. The voltage used will be individualized to each patient, based upon the voltage necessary to slow the sinus rate during testing.
Sham Comparator: Sham LLVNS; n=100 patients will be randomized to sham LLVNS, with the clip applied but no stimulation delivered.	Device: Sham LLVNS; A clip will be applied to the ear, but no stimulation will be delivered throughout the procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence/Burden of Postoperative Atrial Fibrillation	Inpatient hospitalization approximately 3 to 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative morbidity	The incidence of complications during the index hospitalization and one year after surgery	Inpatient hospitalization approximately 3 to 7 days, and one year after surgery
Postoperative mortality	The incidence of complications during the index hospitalization and one year after surgery	Inpatient hospitalization approximately 3 to 7 days, and one year after surgery
Serologic Markers of Inflammation	Cytokine levels, measured in pg/mL	Inpatient hospitalization approximately 3 to 7 days

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Joseph P Mathew, MD, MHS, MBA, Duke University

Publications and helpful links

General Publications

• Stavrakis S, Humphrey MB, Scherlag BJ, Hu Y, Jackman WM, Nakagawa H, Lockwood D, Lazzara R, Po SS. Low-level transcutaneous electrical vagus nerve stimulation suppresses atrial fibrillation. J Am Coll Cardiol. 2015 Mar 10;65(9):867-75. doi: 10.1016/j.jacc.2014.12.026.

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Actual): February 21, 2020
• Study Completion (Actual): February 21, 2020

Study Registration Dates

• First Submitted: April 13, 2016
• First Submitted That Met QC Criteria: May 23, 2016
• First Posted (Estimate): May 26, 2016

Study Record Updates

• Last Update Posted (Actual): April 6, 2020
• Last Update Submitted That Met QC Criteria: April 3, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Autonomic; Postoperative atrial fibrillation; Vagal nerve stimulation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Inflammation; Atrial Fibrillation; Postoperative Complications
• Other Study ID Numbers: Pro00071148

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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