Temporary Autonomic Blockade to Prevent Atrial Fibrillation After Cardiac Surgery

NCT02498769 | Completed Phase 1 Results DMC

• 1 other identifier: Pro00061607
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Atrial Fibrillation

Keywords

Cardiac Surgery; Postoperative Complications; Autonomic Nerve Block

Outcome Measures

Primary Outcomes (1)

• Time to In-hospital Post-operative Atrial Fibrillation (POAF)

  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 Outcomes (3)

• Number of Participants With In-hospital POAF

  The incidence of in-hospital POAF will be tracked throughout the hospitalization (up to two weeks)

• Length of Stay

  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

  Adverse events from the time of surgery through hospital discharge, up to 2 weeks

Study Arms (2)

Epicardial Botulinum

EXPERIMENTAL

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

Epicardial Placebo

PLACEBO COMPARATOR

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

Interventions

Botulinum Toxin Type A DRUG

The botulinum toxin will be injected into epicardial fat pads shortly after cardiopulmonary bypass is initiated.

Also known as: Botox, Onabotulinumtoxin A

Epicardial Botulinum

Placebo DRUG

Also known as: normal saline

Epicardial Placebo

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• \< 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

Sponsors & Collaborators

• Joseph Mathew, M.D.: lead
• Foundation for Anesthesia Education and Research: collaborator
• American Heart Association: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (2)

• Oh S, Choi EK, Zhang Y, Mazgalev TN. Botulinum toxin injection in epicardial autonomic ganglia temporarily suppresses vagally mediated atrial fibrillation. Circ Arrhythm Electrophysiol. 2011 Aug;4(4):560-5. doi: 10.1161/CIRCEP.111.961854. Epub 2011 Jun 9.

  PMID: 21659633 BACKGROUND

• Pokushalov E, Kozlov B, Romanov A, Strelnikov A, Bayramova S, Sergeevichev D, Bogachev-Prokophiev A, Zheleznev S, Shipulin V, Salakhutdinov N, Lomivorotov VV, Karaskov A, Po SS, Steinberg JS. Botulinum toxin injection in epicardial fat pads can prevent recurrences of atrial fibrillation after cardiac surgery: results of a randomized pilot study. J Am Coll Cardiol. 2014 Aug 12;64(6):628-9. doi: 10.1016/j.jacc.2014.04.062. No abstract available.

  PMID: 25104535 BACKGROUND

MeSH Terms

Conditions

Atrial Fibrillation; Postoperative Complications

Interventions

Botulinum Toxins, Type A; Saline Solution

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Joseph P Mathew Professor of Anesthesiology and Chairman Department of Anesthesiology
• Organization: Duke University Health System

joseph.mathew@duke.edu

919-681-6646

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Jerry Reves, MD, Professor of Cardiac Anesthesiology and Chairman, Department of Anesthesiology

Study Record Dates

• First Submitted: July 8, 2015
• First Posted: July 15, 2015
• Study Start: September 1, 2015
• Primary Completion: September 28, 2017
• Study Completion: December 1, 2018
• Last Updated: February 22, 2019
• Results First Posted: December 7, 2018

Record last verified: 2019-02

Locations

US (1)