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    The EU Clinical Trials Register currently displays   43857   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2018-002541-11
    Sponsor's Protocol Code Number:P170912J
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2019-02-05
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedFrance - ANSM
    A.2EudraCT number2018-002541-11
    A.3Full title of the trial
    Prevention of post-operative Atrial Fibrillation by BOTulinum toxin injections into epicardial fat pads around pulmonary veins in patients undergoing cardiac surgery
    Prévention de la Fibrillation Atriale postopératoire par l’injection de Toxine BOtulique autour des veines pulmonaires chez les patients ayant une chirurgie cardiaque
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Prevention of post-operative Atrial Fibrillation by BOTulinum toxin injections into epicardial fat pads around pulmonary veins in patients undergoing cardiac surgery
    Prévention de la Fibrillation Atriale postopératoire par l’injection de Toxine BOtulique autour des veines pulmonaires chez les patients ayant une chirurgie cardiaque
    A.3.2Name or abbreviated title of the trial where available
    BOTAF
    BOTAF
    A.4.1Sponsor's protocol code numberP170912J
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
    B.1.3.4CountryFrance
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportMinistry of Health
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
    B.5.2Functional name of contact pointDRCI Hôpital St Louis
    B.5.3 Address:
    B.5.3.1Street Address1 av. Claude Vellefaux
    B.5.3.2Town/ cityPARIS
    B.5.3.3Post code75010
    B.5.3.4CountryFrance
    B.5.4Telephone number3301 44 84 17 38
    B.5.5Fax number3301 44 84 17 01
    B.5.6E-mailjosephine.braun@aphp.fr
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Xeomin® 200 U
    D.2.1.1.2Name of the Marketing Authorisation holderMerz Pharmaceuticals GmbH
    D.2.1.2Country which granted the Marketing AuthorisationFrance
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameXEOMIN
    D.3.4Pharmaceutical form Powder for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPInfiltration
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product Yes
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboPowder for solution for injection
    D.8.4Route of administration of the placeboInfiltration
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Adult patients with indication for conventional cardiac surgery (CABG, aortic replacement, or ascending aorta surgery) will be eligible
    Seront éligibles : les patients adultes (>/= 18 ans) avec indication à une chirurgie cardiaque selon les recommandations de la Société Européenne de Cardiologie (ESC) : pontages coronaires, remplacements valvulaires aortiques, remplacements de l’aorte ascendante
    E.1.1.1Medical condition in easily understood language
    Adult patients with indication for conventional cardiac surgery
    Patients adultes avec indication à une chirurgie cardiaque selon les recommandations de la Société Européenne de Cardiologie
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10067824
    E.1.2Term Prophylaxis against atrial fibrillation
    E.1.2System Organ Class 100000004865
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The main objective of this trial is 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 months following cardiac surgery.
    L’objectif principal de cette étude est de montrer l’efficacité de la Toxine Botulique, injectée dans la graisse épicardique des veines pulmonaires en per-opératoire, dans la prévention de la FA post-opératoire dans les 3 mois, chez des patients bénéficiant d’une chirurgie cardiaque
    E.2.2Secondary objectives of the trial
    Secondary objectives are to evaluate feasibility and tolerance, i.e. to assess the prevention of atrial tachyarrhythmia (not only AF but also atrial flutter, atrial tachycardia), safety of the surgical procedure, and to assess the total cost and incremental cost effectiveness.
    Les objectifs secondaires sont d’évaluer :
    - la tolérance de la procédure
    - l’efficacité dans la prévention de toutes arythmies atriales confondues : FA, flutter auriculaire, tachycardie atriale focale
    - les coûts globaux à 1 an et le rapport coût/efficacité
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Indication for cardiac surgery (CABG, aortic valve repair or replacement surgery, ascending aorta surgery), according to the European Heart Association guidelines.
    - Patients in hemodynamically stable condition.
    - Sinus rhythm at moment of randomisation.
    - Age: ≥18 to ≤80 years old.
    - Negative serum or urinary β-hCG for premenopausal women.
    - Patients able to attend several consultations at the centre.
    - Informed consent signed.
    - Affiliation to French social security regime.
    - Indication à une chirurgie cardiaque (pontages coronaires, remplacement valvulaire aortique ou réparation valvulaire, chirurgie de l’aorte ascendante), selon les recommandations de l’ESC
    - Patient stable sur le plan hémodynamique
    - Rythme sinusal au moment de la randomisation
    - Patient âgé de 18 à 80 ans inclus
    - Dosage β-hCH (urine ou sérum) négatif pour les femmes pré-ménopausées
    - Patients pouvant se rendre aux consultations du centre recruteur
    - Consentement éclairé signé
    - Affiliation au régime de sécurité sociale
    E.4Principal exclusion criteria
    - Previous cardiac surgery.
    - Preoperative history of 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.
    - Protected populations e.g. breastfeeding women, patients under legal tutorship or curatorship.
    - Participation in another interventional trial.
    - Unwillingness to participate.
    - Contraindications to botulinum toxin under investigation or to the excipients: known hypersensitivity.
    - Antecedent de chirurgie cardiaque
    - Fibrillation atriale ou arythmie atriale persistante en pré-opératoire
    - Antécédent ou indication à une procédure d’isolation des veines pulmonaires
    - Patient sous anti-arythmique de classe I ou III non arrêté depuis 5 demies vies (1 an pour l’Amiodarone).
    - Chirurgie mitrale ou tricuspide
    - Cardiopathie congénitale complexe
    - Maladie neuro-musculaire
    - femme allaitante, patient sous tutelle ou curatelle.
    - Participation à une autre étude interventionnelle
    - Refus de participation
    - Hypersensibilité connue à la toxine botulique
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is the incidence of new onset of postoperative AF in patients undergoing cardiac surgery at 3 months defined as atrial arrhythmia during at least 30 seconds continuously.
    Two blinded cardiologists will independently adjudicate the primary end point.
    Le critère principal est l’incidence de la survenue d’une fibrillation atriale, définie par une arythmie atriale de plus de 30 secondes consécutives, durant les 3 premiers mois après une chirurgie cardiaque.

    2 cardiologues indépendants adjudiqueront les évènements survenus.
    E.5.1.1Timepoint(s) of evaluation of this end point
    at 3 months
    à 3 mois
    E.5.2Secondary end point(s)
    - Death rate at 12 months.
    - Rate of major adverse cardiovascular events at 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.
    - Adverse events (AE) and serious adverse events (SAE) by treatment group.
    - Incidence of atrial tachyarrhythmia including atrial fibrillation, but also atrial flutter and atrial tachycardia at 3 months, and each arrhythmia individually.
    - Incidence of new onset of postoperative AF depending on the following subgroups: age, gender, heart failure (defined by left ventricular ejection fraction < 35%), left atrial enlargement (LA volume index > 52 mL/m2) or LA diameter index > 48 mm/m2, EuroSCORE 2, eGFR < 60 mL/min / 1.73m2.
    - Intervals from end of surgery to extubation and discharge from intensive care unit.
    - Duration of the hospital stay from randomisation to the time of eligibility for discharge (postoperative length of stay).
    - Unplanned readmission rate at 3 months and 12 months for cardiovascular cause or haemorrhage.
    - Number of antiarrhythmic drugs and curative anticoagulation treatments within 3 months following cardiac surgery.
    - Total hospital cost: initial admission and readmissions for cardiovascular cause.
    - Incremental cost effectiveness ratio (additional cost per additional survival, additional QALY or per adverse event recognised).
    - Mortalité à 1 an
    - Taux d’événements indésirables majeurs à 3 mois par groupe de traitement : troubles de la conduction de haut degré (comme bloc atrio-ventriculaire) ou nécessité de mise en place d’un pace maker transitoire ou définitif, insuffisance cardiaque congestive, saignement majeur, accident vasculaire cérébral ou accident embolique systémique
    - Evénements indésirables graves et non graves par groupe de traitement
    - Incidence de toute arythmie atriale confondue (FA, flutter auriculaire, tachycardie atriale focale) à 3 mois et par type d’arythmie.
    - Incidence de la FA par sous-groupes : âge, sexe, FEVG < ou > à 35%, taille de l’oreillette gauche (diamètre indexé > 48 mm/m2 _ volume indexé > 52 mL/m2), EuroSCORE 2, eGFR<60 mL/min/1.73m2.
    - Durée d’intubation et du séjour en réanimation.
    - Durée d’hospitalisation (entre la randomisation et la sortie)
    - Taux de réhospitalisations non programmées dans les 3 premiers mois pour cause cardio-vasculaire ou saignement.
    - Recours aux anti-arythmiques ou à une anticoagulation curative dans les 3 mois post-opératoires.
    - Coût global : hospitalisation initiale et réhospitalisations pour causes cardio-vasculaires ou saignements.
    - Rapport coût efficacité
    E.5.2.1Timepoint(s) of evaluation of this end point
    at 3 months and 12 months
    à 3 mois et 12 mois
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis Yes
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned6
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    Dernière Visite Dernier Patient
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months48
    E.8.9.1In the Member State concerned days
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) No
    F.1.2.1Number of subjects for this age range: 40
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 60
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state220
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2019-04-05
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-06-06
    P. End of Trial
    P.End of Trial StatusOngoing
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