Prevention Atrial Fibrillation by BOTulinum Toxin Injections (BOTAF)

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

220 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-09-30

Study Completion Date

2026-09-30

Brief Summary

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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.

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Detailed Description

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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.

Conditions

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Cardiac Surgery

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

The study is a double-blind multicenter randomized trial comparing treatment with botulinum toxin to normal saline (placebo) on top of usual treatment to prevent atrial fibrillation in patients undergoing cardiac surgery (coronary artery bypass graft surgery (CABG), aortic valve surgery, or ascending aorta surgery).

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Botulinum toxin

All patients from the experimental group will receive botulinum toxin (Xeomin®, incobotulinumtoxin A, Merz Pharma GmbH \& Co KGaA, Germany; 200 U dissolved in 4 mL of 0.9% normal saline and 50 U/1 mL will be injected at each fat pad).

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.

The whole estimated dosage would be therefore 200 units of incobotulinumtoxin A,

Group Type EXPERIMENTAL

Botulinum Toxin Type A Injection [Xeomin]

Intervention Type 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.

Placebo

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 dissolved in 4 mL of 0.9% normal saline will be injected into the entire visible area of the 4 major epicardial fat pads as follows (1 mL at each fat pad).

Group Type PLACEBO_COMPARATOR

Drug placebo

Intervention Type 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).

Interventions

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Botulinum Toxin Type A Injection [Xeomin]

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.

Intervention Type DRUG

Drug placebo

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).

Intervention Type OTHER

Other Intervention Names

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Xeomin

Eligibility Criteria

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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)

Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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FLORENS Emmanuelle, MD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique Hopitaux de Paris (APHP)

Locations

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