Botulinum toxin type A (AGN-151607) for the prevention of post operative atrial fibrillation in patients undergoing open-chest cardiac surgery

Phase 1

• Conditions: Post-operative atrial fibrillation (POAF); MedDRA version: 20.0Level: PTClassification code 10003658Term: Atrial fibrillationSystem Organ Class: 10007541 - Cardiac disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2017-004399-68-GB
• Lead Sponsor: Allergan Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-09-20
• Last Update Posted: 3 November 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 330

Inclusion Criteria

55 to 90 years of age, inclusive, at the time of signing the informed consent

Scheduled to undergo open-chest cardiac surgery. Includes: coronary artery bypass graft (CABG) and/or valve repair/replacement (inclusionary valve repair/replacement procedures for the primary reason for surgery include: aortic or mitral valve repair/replacement; combination of aortic and tricuspid valve repair/replacement;
combination of mitral and tricuspid valve repair/replacement;
CABG/valve combination procedures [when valvular procedure is one of the 4 sub-bulleted procedures immediately above];
left atrial appendage [LAA] procedures are allowed if CABG and/or valve repair/replacement is the qualifying surgical procedure, but is not a qualifying surgical procedure on its own).

In sinus rhythm for the last 48 hours prior to randomization based on standard-of-care assessments and study ECGs (note: continuous ECG monitoring for 48 hours is not required; prior history of paroxysmal AF is acceptable)

Willing to wear an electrocardiogram (ECG) patch for a full 30 days post-surgery and for 7 days after each study visit
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 65
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion Criteria

• Any medical condition that may put the participant at increased risk with exposure to botulinum toxin type A, including diagnosed muscular dystrophy (eg, Duchenne's muscular dystrophy), myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, mitochondrial disease, or any other significant disease which might interfere with neuromuscular function
• Participants with presence or history of any of the following within 3 months prior to the Day 1 visit that may indicate a vulnerable respiratory state per the investigator's clinical judgment: aspiration pneumonia, lower respiratory tract infections, uncontrolled asthma, severe chronic obstructive pulmonary disease or otherwise compromised respiratory
Function
• Permanent/persistent AF
• Has a known allergy or sensitivity to any botulinum toxin type A preparation; has a known allergy or sensitivity to medical adhesive (eg, ECG patch adhesive; hydrogel based adhesive)
• Severe (> 55mm left atrial diameter) left atrial enlargement
• Left ventricular ejection fraction (LVEF) < 25%; presence or history of symptomatic atrioventricular block > 1st degree within the last 30 days (note: presence of a pacemaker is not exclusionary per se)
• Exclusionary valve repair/replacement procedures include combination of aortic and mitral valve repair/replacement; isolated tricuspid valve repair/replacement.
• Prior or concomitant therapy with Class I or III antiarrhythmic drugs unless proper washout was documented
• Botulinum toxin type A (of any serotype) use within 6 months of randomization
• Has been immunized for any botulinum toxin type A serotype as determined by participant medical history
• Preoperative need for inotropes/vasopressors or intra-aortic balloon pump
• Prior open-chest, sternotomy cardiac surgery
• History of ablation for AF
• Planned ablation procedure for AF at the time of surgery
• Emergency surgery
• Impaired prognosis defined as EuroSCORE II > 7% perioperative mortality at screening is exclusionary

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified