Cardiac SurgeryPhase 3BOTAFNCT04075981
Prevention Atrial Fibrillation by BOTulinum Toxin Injections (BOTAF)
A Phase 3 study testing Botulinum Toxin Type A Injection [Xeomin] in people with Cardiac Surgery, run by Assistance Publique - Hôpitaux de Paris at 7 sites in France.
Trial summary
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%. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Cardiac Surgery
- What is being tested?
- Botulinum Toxin Type A Injection [Xeomin]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 220 participants
- Where
- 7 sitesFrance
- Study dates
- 30 Sep 2019to 22 Sep 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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)
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
France7 sites
Corentin Celton
Issy-les-Moulineaux, France
Hôpital Marie Lannelongue
Le Plessis-Robinson, France
CHU Limoges
Limoges, France
Hôpital Saint-Joseph
Marseille, Provence-Alpes-Côte d'Azur Region, 13008
Clinique Ambroise Paré
Neuilly-sur-Seine, Île-de-France Region, 92200
Institut Mutualiste Montsouris
Paris, Île-de-France Region, 75014
Hôpital Européen Georges Pompidou
Paris, Île-de-France Region, 75015
About this study
Official title: Prevention of Post-operative Atrial Fibrillation by BOTulinum Toxin Injections Into Epicardial Fat Pads Around Pulmonary Veins in Patients Undergoing Cardiac Surgery"
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.
Read the detailed 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.
- Conditions
- Cardiac Surgery
- Being tested
- Botulinum Toxin Type A Injection [Xeomin], Drug placebo
- Keywords
- Xeomin®, Botox, Botulinum, Atrial Fibrillation, Cardiac surgery
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Botulinum Toxin Type A Injection [Xeomin]Drug
Also called 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.
Drug placeboOther
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).
| Study group | Role | What they receive |
|---|---|---|
| Botulinum toxin | Experimental | 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, Receives: Drug: Botulinum Toxin Type A Injection [Xeomin] |
| Placebo | Placebo comparator | 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). Receives: Other: Drug placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants presenting at least one episode of atrial fibrillation (more than 30 seconds), during the first 3 weeks after cardiac surgery
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.
Measured: 3 weeks
Secondary outcomes (9)
Death rate
Death rate at 12 months
Measured: 12 months
Number of participants presenting at least one episode of atrial fibrillation (more than 30 seconds), during the first 3 monthes after cardiac surgery
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.
Measured: 3 months
Number of patients presenting a cardiovascular event as conduction troubles, congestive heart failure, major bleeding, stroke, and arterial thromboembolic events
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.
Measured: 3 months
Incidence of atrial tachyarrhythmia / Flutter
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.
Measured: 3 months
New onset of postoperative AF
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
Measured: 3 months
End of surgery until discharge (intervals from end of surgery to extubation, in hours)
Mechanical ventilation duration and postoperative length of stay in intensive care unit and in hospital
Measured: 10 days
Readmission rate
Unplanned readmission rate at 3 months and 12 months for cardiovascular cause or haemorrhage.
Measured: 3 and 12 months
Antiarrhythmic drugs
Number of antiarrhythmic drugs and curative anticoagulation within 3 months following cardiac surgery.
Measured: 3 months
total hospital cost
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).
Measured: twelve months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2019
- Study start30 Sep 2019
- Primary completion13 Oct 2025
- Study completion22 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiac SurgeryStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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).
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 220 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Merz Pharmaceuticals, Ministry of Health, France
- Responsible party
- Sponsor
- Investigators
- FLORENS Emmanuelle, MD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04075981
- Sponsor's protocol ID
- P170912J
- Other IDs
- PHRCN-17-0371
- Acronym
- BOTAF
- Status last verified
- Jun 2026
- First submitted
- 19 Aug 2019
- Last updated
- 1 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individuel participant data that underlie results in publication could be shared Individuel participant data detailed in meta analysis protocol could be shared
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Post-operative Atrial Fibrillation by BOTulinum Toxin Injections Into Epicardial Fat Pads Around Pulmonary Veins in Patients Undergoing Cardiac Surgery"
- ClinicalTrials.gov ID
- NCT04075981
- Acronym / sponsor ID
- BOTAF / P170912J
- Conditions
- Cardiac Surgery
- Keywords
- Xeomin®, Botox, Botulinum, Atrial Fibrillation, Cardiac surgery
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 220 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Merz Pharmaceuticals, Ministry of Health, France
- Study start
- 30 Sep 2019 (actual)
- Primary completion
- 13 Oct 2025 (actual)
- Study completion
- 22 Sep 2026 (estimated)
- First posted
- 3 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- 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).
| Arm | Type | Receives |
|---|---|---|
| Botulinum toxin | Experimental | Drug: Botulinum Toxin Type A Injection [Xeomin]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, |
| Placebo | Placebo comparator | Other: Drug placeboAll 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). |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Botulinum Toxin Type A Injection [Xeomin]Also: XeominBefore 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. | Drug | Botulinum toxin |
| Drug placeboAll 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). | Other | Placebo |
Primary outcome
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.
9 secondary outcomes
Death rate
Time frame: 12 months
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
Number of patients presenting a cardiovascular event as conduction troubles, congestive heart failure, major bleeding, stroke, and arterial thromboembolic events
Time frame: 3 months
Incidence of atrial tachyarrhythmia / Flutter
Time frame: 3 months
New onset of postoperative AF
Time frame: 3 months
End of surgery until discharge (intervals from end of surgery to extubation, in hours)
Time frame: 10 days
Readmission rate
Time frame: 3 and 12 months
Antiarrhythmic drugs
Time frame: 3 months
total hospital cost
Time frame: twelve months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2026.
- Individual participant dataSharing planned: Yes. Individuel participant data that underlie results in publication could be shared Individuel participant data detailed in meta analysis protocol could be shared
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
FLORENS Emmanuelle, MD principal investigator
Assistance Publique - Hôpitaux de Paris
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Botulinum Toxin Type A Injection [Xeomin] in people with Cardiac Surgery, run by Assistance Publique - Hôpitaux de Paris at 7 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 1 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2026.