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

NCT ID: NCT03779841

Last Updated: 2024-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 323 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-01
• Study Completion Date: 2023-03-06

Brief Summary

This was 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.

Conditions

Post-Operative Atrial Fibrillation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

AGN-151607 (250 U)

Injections of 50 U were made into each 1 of 5 fat pads. The total injection volume into each fat pad was 1 mL. One-time treatment.

Group Type: EXPERIMENTAL

AGN-151607

Intervention Type: DRUG

Injections were made into each 1 of 5 fat pads. The total injection volume into each fat pad was 1 mL. One-time treatment.

AGN-151607 (125 U)

Injections of 25 U were made into each 1 of 5 fat pads. The total injection volume into each fat pad was 1 mL. One-time treatment.

Group Type: EXPERIMENTAL

AGN-151607

Intervention Type: DRUG

Injections were made into each 1 of 5 fat pads. The total injection volume into each fat pad was 1 mL. One-time treatment.

Placebo

Injections of placebo were made into each 1 of 5 fat pads. The total injection volume into each fat pad was 1 mL. One-time treatment.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Injections of placebo were made into each 1 of 5 fat pads. The total injection volume into each fat pad was 1 mL. One-time treatment.

Interventions

AGN-151607

Injections were made into each 1 of 5 fat pads. The total injection volume into each fat pad was 1 mL. One-time treatment.

Intervention Type: DRUG

Placebo

Injections of placebo were made into each 1 of 5 fat pads. The total injection volume into each fat pad was 1 mL. One-time treatment.

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

ABBVIE INC.

Role: STUDY_DIRECTOR

AbbVie

Locations

Stanford University School of Med /ID# 236922

Stanford, California, United States

Yale New Haven Hospital - Yale School of Medicine /ID# 238221

New Haven, Connecticut, United States

Medstar Washington Hospital Center /ID# 234322

Washington D.C., District of Columbia, United States

Emory Saint Joseph's Hospital /ID# 234334

Atlanta, Georgia, United States

Lutheran Medical Group /ID# 237990

Fort Wayne, Indiana, United States

Ochsner Medical Center /ID# 238004

New Orleans, Louisiana, United States

University of Maryland Medical Center /ID# 234352

Baltimore, Maryland, United States

University of Michigan /ID# 236228

Ann Arbor, Michigan, United States

Washington University-School of Medicine /ID# 238121

St Louis, Missouri, United States

Dartmouth-Hitchcock Medical Center /ID# 237530

Lebanon, New Hampshire, United States

Icahn School of Medicine at Mount Sinai - The Mount Sinai Medical Center /ID# 234449

New York, New York, United States

Mission Hospital /ID# 237231

Asheville, North Carolina, United States

Duke University Medical Center /ID# 234314

Durham, North Carolina, United States

East Carolina University /ID# 237820

Greenville, North Carolina, United States

Ohio State University Medical Center /ID# 234408

Columbus, Ohio, United States

Medical University of South Carolina /ID# 236476

Charleston, South Carolina, United States

Baylor Scott & White Research Institute /ID# 235937

Plano, Texas, United States

University of Utah /ID# 237601

Salt Lake City, Utah, United States

University of Virginia /ID# 237611

Charlottesville, Virginia, United States

Medizinische Universitaet Wien /ID# 238259

Vienna, Vienna, Austria

University of Ottawa Heart Institute /ID# 236012

Ottawa, Ontario, Canada

Toronto General Hospital /ID# 237680

Toronto, Ontario, Canada

Montreal Heart Insitute /ID# 234859

Montreal, Quebec, 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

Institut universitaire de cardiologie et de pneumologie de Québec - Université L /ID# 237166

Québec, Quebec, Canada

Asklepios Klinik Harburg-Hamburg /ID# 234855

Hamburg, , Germany

ASST degli Spedali Civili di Brescia /ID# 234861

Brescia, , Italy

Academisch Medisch Centrum /ID# 237113

Amsterdam, , Netherlands

Hospital Clínic. University of Barcelona /ID# 234853

Barcelona, , Spain

Orebro University Hospital Sweden /ID# 236047

Örebro, Örebro County, Sweden

University Hospital Plymouth NHS Trust /ID# 234423

Plymouth, , United Kingdom

Countries

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

References

Piccini JP, Ahlsson A, Dorian P, Gillinov MA, Kowey PR, Mack MJ, Milano CA, Perrault LP, Steinberg JS, Waldron NH, Adams LM, Bharucha DB, Brin MF, Ferguson WG, Benussi S. Design and Rationale of a Phase 2 Study of NeurOtoxin (Botulinum Toxin Type A) for the PreVention of Post-Operative Atrial Fibrillation - The NOVA Study. Am Heart J. 2022 Mar;245:51-59. doi: 10.1016/j.ahj.2021.10.114. Epub 2021 Oct 20.

Reference Type: DERIVED

PMID: 34687654 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-004399-68

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1925-201-008

Identifier Type: -

Identifier Source: org_study_id