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NCT Number: NCT04075981

Prevention Atrial Fibrillation by BOTulinum Toxin Injections (BOTAF)

Over the past few years, research has focused on the prevention of atrial fibrillation (AF) after cardiac surgery, but highly effective interventions are still missing. Postoperative AF remains the most common complication after cardiac surgery, with an incidence of 10 to 50%. This complication is usually a transient condition that resolves spontaneously but it has major adverse consequences for patients and the health care system, including increased rates of death, complications (strokes), and hospitalisations with inflated costs.

Recently, animal studies have demonstrated that neurotoxins such as botulinum toxin (BTX) injected into fat pads could suppress AF inducibility by parasympathetic activation. Botulinum toxin injection in fat pads has been studied in the dog's heart and could be associated with the reduction of atrial fibrillation in postoperative cardiac surgery. One pilot study has demonstrated the feasibility and safety of this technique in the human heart.

The investigators hypothesize that botulinum toxin injection may substantially reduce postoperative AF during the first postoperative month after cardiac surgery without any serious adverse events. By the suppression of ganglionic plexi (GP) activity in the epicardial fat pads, mild term antiarrhythmic effects can be achieved with fewer antiarrhythmic drugs and anticoagulant treatment.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Cardiac Surgery Arrhythmias, Cardiac Atrial Fibrillation Cardiovascular Diseases Heart Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Corentin Celton, Issy-les-Moulineaux, France

Loading trial locations.

About this study

Botulinium toxin use has been developed with success in wide-ranging fields (neurology, otorhinolaryngology, gynaecology, urology, plastic surgery, pain therapy), but not in cardiology.

In the cardio-vascular field, only one pilot study on man has shown its utility in the prevention of atrial fibrillation by blocking the triggering through the sympathic and parasympathic systems. The investigators need to assess its potential benefits to prevent postoperative atrial tachyarrhythmia in a randomised multicentre study, with an expected impact of approximately 30,000 patients per years in France undergoing these types of cardiac surgery.

The investigators hypothesize that botulinum toxin injection may substantially reduce postoperative AF during the first 3 weeks after cardiac surgery without any serious adverse events. By the suppression of ganglionic plexi (GP) activity in the epicardial fat pads, mild term antiarrhythmic effects can be achieved with fewer antiarrhythmic drugs and anticoagulant treatment.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Indication for cardiac surgery (CABG, aortic valve repair or aortic valve replacement excluding the sutureless valve, ascending aorta surgery), according to the European Heart Association guidelines.
  • Patients in hemodynamically stable condition.
  • Sinus rhythm at moment of randomisation (ECG).
  • Age: ≥18 to ≤80 years old.
  • Negative serum or urinary β-hCG for women of child-bearing potential.
  • Patients able to attend several consultations at the centre.
  • Informed consent signed.
  • Affiliation to French social security regime.

Exclusion criteria

  • Previous cardiac surgery.
  • Persistent AF or atrial tachycardia.
  • Planned maze procedure or pulmonary vein (PV) isolation.
  • Use of class I or III antiarrhythmic drugs within 5 elimination half-life of the drug (for amiodarone: one year).
  • Mitral or tricuspid valve surgery.
  • Congenital cardiomyopathy.
  • Neuro-muscular disease (including disorders of pre-operative swallowing).
  • Protected populations e.g. minor patient, breastfeeding women, patients under legal guardianship, curatorship or legal protection. .
  • Participation in another interventional trial.
  • Unwillingness to participate.
  • Contraindications to botulinum toxin under investigation or to the excipients: known hypersensitivity.
  • Patient with active endocarditis Minimal invasive surgery (ministernotomy)

Treatment and study plan

Botulinum Toxin Type A Injection [Xeomin]

Drug

Before the main stage of the surgery, botulinum toxin will be injected into the entire visible area of the 4 major epicardial fat pads, during extra corporal circulation and before aortic cross clamping in order to reduce the time of ischemia.

Other names: Xeomin

Drug placebo

Other

All patients from the control group will receive placebo. Before the main stage of the surgery, during extra corporal circulation and before aortic cross clamping, the placebo will be injected into the entire visible area of the 4 major epicardial fat pads as follows (1 mL at each fat pad).

Primary outcomes

  1. Number of participants presenting at least one episode of atrial fibrillation (more than 30 seconds), during the first 3 weeks after cardiac surgery

    Time frame: 3 weeks

    An episode of AF will be considered part of the primary outcome analyses if it last at least 30 seconds continuously within 21 days after cardiac surgery and is documented by any form of monitoring, regardless of symptoms. The definition of atrial fibrillation (at least 30 seconds continuously) results from recent publications and AF definition in the cardiovascular field64.

    This endpoint will be measured through both holter ECG Spiderflash-t recorder during the first 21 days post-op and ECG daily monitoring during the first 7 days after surgery.

Secondary outcomes

  1. Death rate

    Time frame: 12 months

    Death rate at 12 months

  2. Number of participants presenting at least one episode of atrial fibrillation (more than 30 seconds), during the first 3 monthes after cardiac surgery

    Time frame: 3 months

    Incidence of rhythm disorders of postoperative AF in patients undergoing cardiac surgery at 3 months defined as atrial arrhythmia during at least 30 seconds continuously.

  3. Number of patients presenting a cardiovascular event as conduction troubles, congestive heart failure, major bleeding, stroke, and arterial thromboembolic events

    Time frame: 3 months

    conduction troubles such as atrioventricular block or the need for transient or permanent placement of a pacemaker, congestive heart failure, major bleeding, stroke, and arterial thromboembolic events.cardiac surgery at 3 months defined as atrial arrhythmia during at least 30 seconds continuously.

  4. Incidence of atrial tachyarrhythmia / Flutter

    Time frame: 3 months

    Incidence of all atrial tachyarrhythmia including atrial fibrillation, but also atrial flutter and atrial tachycardia 3 months, and each arrhythmia taken individually between the two parallel groups.cardiac surgery at 3 months defined as atrial arrhythmia during at least 30 seconds continuously.

  5. New onset of postoperative AF

    Time frame: 3 months

    Incidence of new onset of postoperative AF depending on the following subgroups: age, gender, heart failure, left atrial enlargement, Euro SCORE 2, renal function, type of surgery

  6. End of surgery until discharge (intervals from end of surgery to extubation, in hours)

    Time frame: 10 days

    Mechanical ventilation duration and postoperative length of stay in intensive care unit and in hospital

  7. Readmission rate

    Time frame: 3 and 12 months

    Unplanned readmission rate at 3 months and 12 months for cardiovascular cause or haemorrhage.

  8. Antiarrhythmic drugs

    Time frame: 3 months

    Number of antiarrhythmic drugs and curative anticoagulation within 3 months following cardiac surgery.

  9. total hospital cost

    Time frame: twelve months

    Initial admission and readmissions for cardiovascular cause, and Incremental cost effectiveness ratio (additional cost per additional survival, additional QALY or per additional adverse event recognised).

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Collaborators

  • Merz Pharmaceuticals
  • Ministry of Health, France

Registry information

Official study title

Prevention of Post-operative Atrial Fibrillation by BOTulinum Toxin Injections Into Epicardial Fat Pads Around Pulmonary Veins in Patients Undergoing Cardiac Surgery"

Acronym: BOTAF

Important dates

Study start
2019
Primary completion
2025
Study completion
2026
First posted
Sep 3, 2019
Registry last updated
Jul 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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