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

NCT03779841 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 1925-201-0082017-004399-68
• Study Type: interventional
• Target: 323
• Locations: 9 countries
• Sites: 32

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With at Least 1 Continuous AF (Atrial Fibrillation or Atrial Flutter) Episode ≥ 30 Seconds During the First 30 Days Post-surgery

  At least one episode of continuous AF (atrial fibrillation or atrial flutter) sustained ≥ 30 seconds documented by monitoring ECG measurements using ECG patches (ePatch) placed on the participant's chest.

  First 30 days following the initial intensive care unit (ICU) admission date after open-chest cardiac surgery.

Secondary Outcomes (16)

• Percentage of Time Spent in Atrial Fibrillation or Atrial Flutter (AF Burden) During the First 30 Days Post-surgery

  First 30 days following the initial ICU admission date after open-chest cardiac surgery.

• Percentage of Participants With at Least 1 Event of Symptomatic AF (Atrial Fibrillation or Atrial Flutter) During the First 30 Days Post-surgery

  First 30 days following the initial ICU admission date after open-chest cardiac surgery.

• Time to First Occurrence of AF (Atrial Fibrillation or Atrial Flutter) During the First 30 Days Post-surgery

  First 30 days following the initial ICU admission date after open-chest cardiac surgery.

• Percentage of Participants With at Least 1 Continuous AF (Atrial Fibrillation or Atrial Flutter) Episode ≥ 2 Minutes During the First 30 Days Post-surgery

  First 30 days following the initial ICU admission date after open-chest cardiac surgery.

• Percentage of Participants With at Least 1 Continuous AF (Atrial Fibrillation or Atrial Flutter) Episode ≥ 5 Minutes During the First 30 Days Post-surgery

  First 30 days following the initial ICU admission date after open-chest cardiac surgery.

Study Arms (3)

AGN-151607 (250 U)

EXPERIMENTAL

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.

Drug: AGN-151607

AGN-151607 (125 U)

EXPERIMENTAL

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.

Drug: AGN-151607

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

AGN-151607 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); AGN-151607 (250 U)

Placebo 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.

Placebo

Eligibility Criteria

• Age: 55 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.
• 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%
• 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

Sponsors & Collaborators

• AbbVie: lead

Study Sites (32)

Stanford University School of Med /ID# 236922

Stanford, California, 94305-2200, United States

Location

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

New Haven, Connecticut, 06510-3206, United States

Location

Medstar Washington Hospital Center /ID# 234322

Washington D.C., District of Columbia, 20010-3017, United States

Location

Emory Saint Joseph's Hospital /ID# 234334

Atlanta, Georgia, 30342-1731, United States

Location

Lutheran Medical Group /ID# 237990

Fort Wayne, Indiana, 46804, United States

Location

Ochsner Medical Center /ID# 238004

New Orleans, Louisiana, 70121-2429, United States

Location

University of Maryland Medical Center /ID# 234352

Baltimore, Maryland, 21201-1544, United States

Location

University of Michigan /ID# 236228

Ann Arbor, Michigan, 48109-5000, United States

Location

Washington University-School of Medicine /ID# 238121

St Louis, Missouri, 63110, United States

Location

Dartmouth-Hitchcock Medical Center /ID# 237530

Lebanon, New Hampshire, 03756, United States

Location

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

New York, New York, 10029, United States

Location

Mission Hospital /ID# 237231

Asheville, North Carolina, 28801, United States

Location

Duke University Medical Center /ID# 234314

Durham, North Carolina, 27705-4410, United States

Location

East Carolina University /ID# 237820

Greenville, North Carolina, 27858, United States

Location

Ohio State University Medical Center /ID# 234408

Columbus, Ohio, 43210, United States

Location

Medical University of South Carolina /ID# 236476

Charleston, South Carolina, 29425, United States

Location

Baylor Scott & White Research Institute /ID# 235937

Plano, Texas, 75093, United States

Location

University of Utah /ID# 237601

Salt Lake City, Utah, 84112-5500, United States

Location

University of Virginia /ID# 237611

Charlottesville, Virginia, 22908, United States

Location

Medizinische Universitaet Wien /ID# 238259

Vienna, Vienna, 1090, Austria

Location

University of Ottawa Heart Institute /ID# 236012

Ottawa, Ontario, K1Y 4W7, Canada

Location

Toronto General Hospital /ID# 237680

Toronto, Ontario, M5G 2C4, Canada

Location

Montreal Heart Insitute /ID# 234859

Montreal, Quebec, H1T 1C8, Canada

Location

CHUM - Centre hospitalier de l'Universite de Montréal /ID# 238163

Montreal, Quebec, H2X 3E4, Canada

Location

CIUSSS du Nord-de-l'ile-de-Montréal_Hopital du Sacré-Coeur de Montréal /ID# 234316

Montreal, Quebec, H4J 1C5, Canada

Location

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

Québec, Quebec, G1V 4G5, Canada

Location

Asklepios Klinik Harburg-Hamburg /ID# 234855

Hamburg, 21075, Germany

Location

ASST degli Spedali Civili di Brescia /ID# 234861

Brescia, 25123, Italy

Location

Academisch Medisch Centrum /ID# 237113

Amsterdam, 1105 AZ, Netherlands

Location

Hospital Clínic. University of Barcelona /ID# 234853

Barcelona, 08039, Spain

Location

Orebro University Hospital Sweden /ID# 236047

Örebro, Örebro County, 702 12, Sweden

Location

University Hospital Plymouth NHS Trust /ID# 234423

Plymouth, PL6 5FP, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 34687654 DERIVED

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

abbvieclinicaltrials@abbvie.com

800-633-9110

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2018
• First Posted: December 19, 2018
• Study Start: March 1, 2019
• Primary Completion: March 24, 2022
• Study Completion: March 6, 2023
• Last Updated: May 14, 2024
• Results First Posted: May 14, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/

Locations

CA (6); GB (1); IT (1); US (19); SE (1); ES (1); AU (1); DE (1); NL (1)