BOTAF - Prevention of post-operative Atrial Fibrillation by BOTulinum toxin injections into epicardial fat pads around pulmonary veins in patients undergoing cardiac surgery

2024-513645-37-00 Protocol P170912J Therapeutic confirmatory (Phase III) Ongoing, recruitment ended

Start 5 Sep 2024 · Status Ongoing, recruitment ended · 1 EU/EEA countries · 7 sites · Protocol P170912J

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ongoing, recruitment ended
Participants planned 220
Countries 1
Sites 7

Adult patients with indication for conventional cardiac surgery (CABG, aortic replacement, or ascending aorta surgery)

To determine the efficacy of Botulinum toxin injection into epicardial fat pads for the prevention of postoperative AF in patients undergoing cardiac surgery within three weeks following cardiac surgery

Key facts

Sponsor
Assistance Publique Hopitaux De Paris
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Cardiovascular Diseases [C14]
Trial duration
5 Sep 2024 → ongoing
Decision date (initial)
2024-09-05
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
French Ministry of Health and Merz Pharma

External identifiers

EU CT number
2024-513645-37-00
EudraCT number
2018-002541-11
ClinicalTrials.gov
NCT04075981

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Prophylaxis

To determine the efficacy of Botulinum toxin injection into epicardial fat pads for the prevention of postoperative AF in patients undergoing cardiac surgery within three weeks following cardiac surgery

Conditions and MedDRA coding

Adult patients with indication for conventional cardiac surgery (CABG, aortic replacement, or ascending aorta surgery)

VersionLevelCodeTermSystem organ class
21.1 LLT 10067824 Prophylaxis against atrial fibrillation 10042613

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

  1. - 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 1

  1. - 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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. The incidence of rhythm disorders of postoperative AF in patients undergoing cardiac surgery at 3 weeks defined as atrial arrhythmia during at least 30 seconds continuously within 21 days after cardiac surgery. It 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. Two blinded cardiologists will independently adjudicate the primary end point.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

XEOMIN 200 unités, poudre pour solution injectable

PRD4411682 · Product

Active substance
Clostridium Botulinum Neurotoxin Type a (150KD), Free of Complexing Proteins
Substance synonyms
IncobotulinumtoxinA, NT 201, Botulinum toxin type A (150 kD), free from complexing proteins
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INFILTRATION
Max daily dose
200 U unit(s)
Max total dose
200 U unit(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
M03AX01 — BOTULINUM TOXIN
Marketing authorisation
34009 550 221 5 2
MA holder
MERZ PHARMACEUTICALS GMBH
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Placebo 1

Placebo of Xeomin 200 U

N/A · Product

Other product name
N/A
Pharmaceutical form
N/A
ATC code
N/A — N/A
Marketing authorisation
N/A
MA holder
N/A
MA country
Iceland
Paediatric formulation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation
Assistance Publique Hopitaux De Paris
Address
Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux
City
Paris Cedex 10
Postcode
75475
Country
France

Scientific contact point

Organisation
Assistance Publique Hopitaux De Paris
Contact name
Dr Emmanuelle FLORENS

Public contact point

Organisation
Assistance Publique Hopitaux De Paris
Contact name
Dr Emmanuelle FLORENS

Locations

1 EU/EEA country · 7 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Ongoing, recruitment ended 220 7
Rest of world 0

Investigational sites

France

7 sites · Ongoing, recruitment ended
Assistance Publique Hopitaux De Paris
Service de chirurgie cardiovasculaire, 20 Rue Leblanc, 75908, Paris Cedex 15
GIE Groupe hospitalier Paris Saint-Joseph/Vinci
Chirurgie Cardiaque Adulte, 133 Avenue De La Resistance, 92350, Le Plessis-Robinson
Centre Hospitalier Et Universitaire De Limoges
Chirurgie thoracique, 2 Avenue Martin Luther King, 87000, Limoges
Assistance Publique Hopitaux De Paris
Réadaptation Cardiaque, 4 Parvis Corentin Celton, 92130, Issy-Les-Moulineaux
Hopital Saint Joseph
Chirurgie cardiaque, 26 Boulevard De Louvain, 13008, Marseille
Institut Mutualiste Montsouris
Chirurgie cardiaque, 42 Boulevard Jourdan, 75014, Paris
Centre Medico Chirurgical Ambroise Pare Hartmann
Chirurgie cardiaque et interventionnelle, 25 Boulevard Victor Hugo, 92200, Neuilly-Sur-Seine

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
France 2024-09-05 2024-09-30 2025-09-23

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol 2024-513645-37-00 7-0
Recruitment arrangements (for publication) K1_Recruitment arrangements 1-0
Subject information and informed consent form (for publication) L1_SIS-ICF adulte 3
Subject information and informed consent form (for publication) L1_SIS-ICF adulte addendum 1
Summary of Product Characteristics (SmPC) (for publication) E2_ SmPC Xeomin 200 U 1
Synopsis of the protocol (for publication) D1_Protocol synopsis_FR 2024-513645-37-00 7-0

Application history

2 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-08-09 France Acceptable
2024-08-26
2024-09-05
2 SUBSTANTIAL MODIFICATION SM-1 2024-10-04 France Acceptable
2024-10-28
2024-11-19