Botulinum Toxin Type A (AGN-151607) for the Prevention of Post-operative Atrial Fibrillation in Adult Participants Undergoing Open-chest Cardiac Surgery (NOVA)

Post-Operative Atrial Fibrillation Clinical Trial

Official title:

A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Efficacy and Safety of Botulinum Toxin Type A (AGN-151607) Injections Into the Epicardial Fat Pads to Prevent Post-Operative Atrial Fibrillation in Patients Undergoing Open-Chest Cardiac Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03779841
• Other study ID #: 1925-201-008
• Secondary ID: 2017-004399-68
• Status: Completed
• Phase: Phase 2
• Start date: March 1, 2019
• Est. completion date: March 2, 2023

Study information

• Verified date: May 2023
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multi-center, randomized, double-blind, placebo-controlled, parallel group, dose-ranging study to evaluate the efficacy and safety of botulinum toxin type A (AGN-151607) injections into the epicardial fat pads, foci of ganglionic plexi, to prevent Post-Operative Atrial Fibrillation (POAF) in patients undergoing open-chest cardiac surgery.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 330
• Est. completion date: March 2, 2023
• Est. primary completion date: March 24, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 90 Years

Eligibility

Inclusion Criteria:

Inclusion Criteria:

• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form.
• Written informed consent from the participant has been obtained prior to any study-related procedures
• Written documentation has been obtained in accordance with the relevant country and local privacy requirements, where applicable (eg. Written Authorization for Use and Release of Health and Research Study Information [US sites] and written Data Protection consent (European Union sites).
• Participants who are 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 valve repair/replacement, 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 or replacement is the qualifying surgical procedure, but is not a qualifying surgical procedure on its own.

• A male participant must agree to use contraception until Day 60 and refrain from donating sperm during this period.
• A female participant is eligible to participate if she is not pregnant (has a negative urine pregnancy result prior to randomization) not breastfeeding, and at least 1 of the following conditions applies: Not a woman of childbearing potential (WOCBP). A WOCBP who agrees to follow the contraceptive guidance until after Day 60.
• 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
• Able, as assessed by the investigator, and willing to follow study instructions and likely to complete required study visit.

Exclusion Criteria:

• Any uncontrolled clinically significant medical condition other than the one under study that, in the investigator's opinion, would put the participant at an unacceptable risk with exposure to botulinum toxin type A.
• Exclusionary valve repair/replacement procedures include: Combination of aortic and mitral valve repair/replacement, Isolated tricuspid valve repair/replacement.
• 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 atrial fibrillation (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 (> 55 mm 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) - 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
• Current enrollment in an investigational drug or device study or participation in such a study within 30 days of entry into this study
• Participants have diagnostic assessments which in the opinion of the investigator prevent participation in the study
• Impaired prognosis defined as EuroSCORE II > 7% perioperative mortality at screening is exclusionary.
• Females who are pregnant, nursing, or planning a pregnancy during the study
• The participant has a condition or is in a situation which, in the investigator's opinion, may put the participant at significant risk, may confound the study results, or may interfere significantly with the participant's participation in the study.

Related Conditions & MeSH terms

• Atrial Fibrillation
• Post-Operative Atrial Fibrillation

Intervention

Drug:
• AGN-151607
Injections will be made into each 1 of 5 fat pads. The total injection volume into each fat pad will be 1 mL. One-time treatment.
• Placebo
Injections of placebo will be made into each 1 of 5 fat pads. The total injection volume into each fat pad will be 1 mL. One-time treatment.

Locations

Country	Name	City	State
Austria	Medizinische Universitaet Wien /ID# 238259	Vienna	Wien
Canada	CHUM - Centre hospitalier de l'Universite de Montréal /ID# 238163	Montreal	Quebec
Canada	CIUSSS du Nord-de-l'ile-de-Montréal_Hopital du Sacré-Coeur de Montréal /ID# 234316	Montreal	Quebec
Canada	Montreal Heart Insitute /ID# 234859	Montreal	Quebec
Canada	University of Ottawa Heart Institute /ID# 236012	Ottawa	Ontario
Canada	Institut universitaire de cardiologie et de pneumologie de Québec - Université L /ID# 237166	Québec	Quebec
Canada	Toronto General Hospital /ID# 237680	Toronto	Ontario
Germany	Asklepios Klinik Harburg-Hamburg /ID# 234855	Hamburg
Italy	ASST degli Spedali Civili di Brescia /ID# 234861	Brescia
Netherlands	Academisch Medisch Centrum /ID# 237113	Amsterdam
Spain	Hospital Clínic. University of Barcelona /ID# 234853	Barcelona
Sweden	Orebro University Hospital Sweden /ID# 236047	Orebro	Orebro Lan
United Kingdom	University Hospital Plymouth NHS Trust /ID# 234423	Plymouth
United States	University of Michigan /ID# 236228	Ann Arbor	Michigan
United States	Mission Hospital /ID# 237231	Asheville	North Carolina
United States	Emory Saint Joseph's Hospital /ID# 234334	Atlanta	Georgia
United States	University of Maryland Medical Center /ID# 234352	Baltimore	Maryland
United States	Medical University of South Carolina /ID# 236476	Charleston	South Carolina
United States	University of Virginia /ID# 237611	Charlottesville	Virginia
United States	Ohio State University Medical Center /ID# 234408	Columbus	Ohio
United States	Duke University Medical Center /ID# 234314	Durham	North Carolina
United States	Lutheran Medical Group /ID# 237990	Fort Wayne	Indiana
United States	East Carolina University /ID# 237820	Greenville	North Carolina
United States	Dartmouth-Hitchcock Medical Center /ID# 237530	Lebanon	New Hampshire
United States	Yale New Haven Hospital - Yale School of Medicine /ID# 238221	New Haven	Connecticut
United States	Ochsner Medical Center /ID# 238004	New Orleans	Louisiana
United States	Icahn School of Medicine at Mount Sinai - The Mount Sinai Medical Center /ID# 234449	New York	New York
United States	Baylor Scott & White Research Institute /ID# 235937	Plano	Texas
United States	Washington University-School of Medicine /ID# 238121	Saint Louis	Missouri
United States	University of Utah /ID# 237601	Salt Lake City	Utah
United States	Stanford University School of Med /ID# 236922	Stanford	California
United States	Medstar Washington Hospital Center /ID# 234322	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Austria,  Canada,  Germany,  Italy,  Netherlands,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants with at least 1 continuous atrial fibrillation (AF) episode = 30 seconds during the first 30 days post-surgery.		30 days
Secondary	Percentage of time spent in AF (AF burden) during the first 30 days post-surgery		30 days
Secondary	Percentage of participants with at least 1 event of symptomatic AF during the first 30 days post-surgery		30 days
Secondary	Time to first occurrence of AF during the first 30 days post-surgery		30 days
Secondary	Percentage of participants with at least 1 continuous AF episode = 2 minutes during the first 30 days post-surgery		30 days
Secondary	Percentage of participants with at least 1 continuous AF episode = 5 minutes during the first 30 days post-surgery		30 days
Secondary	Percentage of participants with at least 1 continuous AF episode = 30 minutes during the first 30 days post-surgery		30 days
Secondary	Percentage of participants with at least 1 continuous AF episode = 1 hour during the first 30 days post-surgery		30 days
Secondary	Percentage of participants with at least 1 continuous AF episode = 4 hours during the first 30 days post-surgery		30 days
Secondary	Percentage of participants with at least 1 continuous AF episode = 24 hours during the first 30 days post-surgery		30 days
Secondary	Percentage of participants with at least 1 continuous AF episode = 6 hours during the first 30 days post-surgery		30 days
Secondary	Percentage of participants with at least 1 continuous AF episode = 12 hours during the first 30 days post-surgery		30 days