Temporary Autonomic Blockade to Prevent Atrial Fibrillation After Cardiac Surgery

February 6, 2019 updated by: Joseph Mathew, M.D.
In this study, the investigators aim to determine whether injecting botulinum toxin into epicardial fat pads is efficacious and safe for decreasing postoperative atrial fibrillation (POAF) after cardiac surgery. The investigators will test the hypothesis that botulinum toxin injected into the epicardial fat pads reduces POAF and length of stay (LOS) without increasing adverse events. This will be a prospective randomized trial of 130 patients undergoing coronary artery bypass graft (CABG), valve surgery or CABG + valve surgery with cardiopulmonary bypass. Patients will be randomized to receive either botulinum toxin (50 units per fat pad, n=65) or normal saline/placebo (1 mL per fat pad, n=65) injected into epicardial fat pads. 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. Based on previous work and a pilot trial showing a pronounced reduction (relative risk reduction 77%) in POAF after injecting botulinum into the epicardial fat pads, the investigators anticipate a significant reduction in the risk for POAF with epicardial botulinum in this cohort, which includes valve surgery patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Purpose of the study: A pilot study to determine whether injecting botulinum toxin into epicardial fat pads is efficacious and safe for decreasing postoperative atrial fibrillation (POAF) after cardiac surgery

Hypothesis to be tested: Botulinum toxin injected into the epicardial fat pads reduces POAF.

Design and Procedures: This will be a prospective randomized pilot trial of 130 patients undergoing coronary artery bypass graft (CABG), valve surgery or CABG + valve surgery via median sternotomy with cardiopulmonary bypass. Patients <50 years of age, with chronic atrial fibrillation, prior cardiac surgery, EF<25%, preoperative inotropic support, hepatic or renal failure, known sensitivity to botulinum toxin, debilitating neuromuscular disease, or those with a history of atrioventricular block will be excluded from the study. Prior to surgery, all patients will have baseline Mini-Mental State Examination (MMSE) and blood sampling from an indwelling arterial line or venipuncture for measurement of inflammatory and genomic markers. Half of the patients will be randomized to receive injection of epicardial botulinum toxin in addition to standard of care, as described below. The other half will receive epicardial injection of normal saline.

Institution of cardiopulmonary bypass will be performed according to the routine surgical protocol. After instituting CPB, botulinum toxin (or normal saline) injections will be performed by the surgeon. This dose was selected given the prior report of its effectiveness in preventing POAF after cardiac surgery in a small pilot study.(Pokushalov et al., 2014) After completion of surgery and separation from CPB, patients will proceed along the institutional Cardiac Surgical Caremap. All patients will be monitored with continuous ECG (telemetry) until hospital discharge. POAF will be diagnosed by telemetry or 12-lead ECG, and will be defined as new-onset if it occurs postoperatively at any time before hospital discharge. POAF, if it occurs, will be treated as per routine of care. POAF will be defined as any detectable atrial fibrillation before discharge that lasts >30 seconds. On postoperative day (POD) 4, a member of the study team will visit each patient to administer the MMSE and capture a 5-minute ECG with a Holter monitor. In addition, patients will be contacted monthly for 4 months and at one year after surgery for follow up, and medical records will be reviewed for evidence of readmissions, arrhythmias, or other adverse events.

Study Type

Interventional

Enrollment (Actual)

130

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

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

Study Locations

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

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

50 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Undergoing cardiac surgery with cardiopulmonary bypass via median sternotomy
  • coronary artery bypass graft (CABG)
  • valve surgery
  • CABG + valve surgery

Exclusion Criteria:

  • < 50years of age
  • > 90years of age
  • chronic AF or AF at the time of screening
  • preoperative heart block (second degree or greater)
  • LVEF < 25%
  • renal failure
  • hepatic failure
  • known sensitivity to Botulinum toxin
  • debilitating neuromuscular disease
  • preoperative need for inotropes/vasopressors or intra-aortic balloon pump
  • planned MAZE procedure
  • history of catheter ablation for AF
  • use of Vaughan-Williams class I or III drugs within 5 elimination half lives (or within 2 months for amiodarone)
  • undergoing minimally-invasive cardiac surgery
  • prior cardiac surgery

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: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Epicardial Botulinum
After instituting cardiopulmonary bypass (CPB), botulinum toxin injections will be performed by the surgeon as follows: Using a standard sterile insulin syringe with a 27g needle, surgeons will inject each of the epicardial fat pads with 50U (1mL) of botulinum toxin (OnabotulinumtoxinA, Botox®). After completion of surgery and separation from CPB, patients will proceed along the institutional Cardiac Surgical Caremap. All patients will be monitored with continuous ECG (telemetry) until hospital discharge. POAF will be diagnosed by telemetry or 12-lead ECG, and will be defined as new-onset if it occurs postoperatively at any time before hospital discharge.
Drug: Botulinum Toxin Type A
The botulinum toxin will be injected into epicardial fat pads shortly after cardiopulmonary bypass is initiated.
Other Names:
  • Botox
  • Onabotulinumtoxin A
Placebo Comparator: Epicardial Placebo
After instituting cardiopulmonary bypass (CPB), placebo (normal saline) injections will be performed by the surgeon as follows: Using a standard sterile insulin syringe with a 27g needle, surgeons will inject each of the epicardial fat pads with 1mL of normal saline. After completion of surgery and separation from CPB, patients will proceed along the institutional Cardiac Surgical Caremap. All patients will be monitored with continuous ECG (telemetry) until hospital discharge. POAF will be diagnosed by telemetry or 12-lead ECG, and will be defined as new-onset if it occurs postoperatively at any time before hospital discharge.
Drug: Placebo
Other Names:
  • normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to In-hospital Post-operative Atrial Fibrillation (POAF)
Time Frame: From the time of ICU arrival until the time of first documented POAF, or discharge whichever came first, assessed up to 2 weeks
Patients will be seen on a daily basis and the timing of POAF compared between groups. The occurrence of in-hospital POAF will be tracked throughout the hospitalization (up to two weeks) and the time from surgery to the first and subsequent episodes of POAF recorded and compared between groups. POAF will be determined by ECG or telemetry.
From the time of ICU arrival until the time of first documented POAF, or discharge whichever came first, assessed up to 2 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With In-hospital POAF
Time Frame: The incidence of in-hospital POAF will be tracked throughout the hospitalization (up to two weeks)
Patients will be seen on a daily basis and the occurrence of POAF compared between groups.
The incidence of in-hospital POAF will be tracked throughout the hospitalization (up to two weeks)
Length of Stay
Time Frame: ICU length of stay was measured from time of surgery to time of ICU discharge. Post-operative length of stay was measured from time of surgery to time of hospital discharge.
Total and ICU length of stay will be determined by examining medical records for the length of inpatient hospitalization, assessed over the entire study period (up to two years). ICU and hospital LOS will be recorded and compared between groups
ICU length of stay was measured from time of surgery to time of ICU discharge. Post-operative length of stay was measured from time of surgery to time of hospital discharge.
Number of Participants With Adverse Events
Time Frame: Adverse events from the time of surgery through hospital discharge, up to 2 weeks
The total number of postoperative complications (including infectious, neurologic, and renal complications, as well as mortality) and the number of subjects with complications will be monitored and compared between groups.
Adverse events from the time of surgery through hospital discharge, up to 2 weeks

Collaborators and Investigators

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

Sponsor

Joseph Mathew, M.D.

Collaborators

American Heart Association
Foundation for Anesthesia Education and Research

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 1, 2015

Primary Completion (Actual)

September 28, 2017

Study Completion (Actual)

December 1, 2018

Study Registration Dates

First Submitted

July 8, 2015

First Submitted That Met QC Criteria

July 13, 2015

First Posted (Estimate)

July 15, 2015

Study Record Updates

Last Update Posted (Actual)

February 22, 2019

Last Update Submitted That Met QC Criteria

February 6, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00061607

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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