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Prevention Atrial Fibrillation by BOTulinum Toxin Injections (BOTAF)

Prevention Atrial Fibrillation by BOTulinum Toxin Injections (BOTAF)

Recruiting
18-80 years
All
Phase 3

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Overview

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.

Description

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.

Eligibility

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)

Study details
    Cardiac Surgery

NCT04075981

Assistance Publique - Hôpitaux de Paris

15 October 2025

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