Botulinum Toxin Type A (AGN-151607) for the Prevention of Post-operative Atrial Fibrillation in Adult Participants Undergoing Open-chest Cardiac Surgery (NOVA)
- Conditions
- Post-Operative Atrial Fibrillation
- Interventions
- Drug: AGN-151607Drug: Placebo
- Registration Number
- NCT03779841
- Lead Sponsor
- AbbVie
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 323
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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AGN-151607 (250 U) AGN-151607 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. AGN-151607 (125 U) AGN-151607 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. Placebo 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants With at Least 1 Continuous AF (Atrial Fibrillation or Atrial Flutter) Episode ≥ 30 Seconds During the First 30 Days Post-surgery First 30 days following the initial intensive care unit (ICU) admission date after open-chest cardiac 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.
- Secondary Outcome Measures
Name Time Method 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. At least 1 event of symptomatic AF (atrial fibrillation or atrial flutter) (symptoms occurring within 2 hours of an AF episode). For symptomatic AF, symptoms that occur in the interval that starts two hours prior to the onset of the AF episode and ends two hours after the conclusion of the AF episode will meet the definition of "within 2 hours of an AF episode".
AF episode ≥ 30 seconds.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. The proportion of time an individual is in AF (atrial fibrillation or atrial flutter) during a monitoring period (expressed as a percentage) calculated as (the total time spent in AF during the first 30 days post-surgery divided by the total time of analyzable data obtained from the ECG patch during the first 30 days post-surgery) multiplied by 100. The calculation excludes continuous AF episodes \< 30 seconds in duration.
Percentage of Participants With at Least 1 Continuous AF (Atrial Fibrillation or Atrial Flutter) Episode ≥ 12 Hours During the First 30 Days Post-surgery First 30 days following the initial ICU admission date after open-chest cardiac surgery. At least one episode of continuous AF (atrial fibrillation or atrial flutter) sustained ≥ 12 hours documented by monitoring ECG measurements using ECG patches (ePatch) placed on the participant's chest.
Percentage of Participants With at Least 1 Continuous AF (Atrial Fibrillation or Atrial Flutter) Episode ≥ 24 Hours During the First 30 Days Post-surgery First 30 days following the initial ICU admission date after open-chest cardiac surgery. At least one episode of continuous AF (atrial fibrillation or atrial flutter) sustained ≥ 24 hours documented by monitoring ECG measurements using ECG patches (ePatch) placed on the participant's chest.
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. At least one episode of continuous AF (atrial fibrillation or atrial flutter) sustained ≥ 2 minutes documented by monitoring ECG measurements using ECG patches (ePatch) placed on the participant's chest.
Percentage of Participants With at Least 1 Continuous AF (Atrial Fibrillation or Atrial Flutter) Episode ≥ 6 Hours During the First 30 Days Post-surgery First 30 days following the initial ICU admission date after open-chest cardiac surgery. At least one episode of continuous AF (atrial fibrillation or atrial flutter) sustained ≥ 6 hours documented by monitoring ECG measurements using ECG patches (ePatch) placed on the participant's chest.
Percentage of Participants With at Least 1 Continuous Atrial Fibrillation (Excluding Atrial Flutter) Episode ≥ 30 Seconds During the First 30 Days Post-surgery First 30 days following the initial ICU admission date after open-chest cardiac surgery. At least one episode of continuous atrial fibrillation (excluding atrial flutter) sustained ≥ 30 seconds documented by monitoring ECG measurements using ECG patches (ePatch) placed on the participant's chest.
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. Amount of time (days) to first AF (atrial fibrillation or atrial flutter) occurrence defined by first episode of AF lasting for ≥ 30 seconds.
Percentage of Participants With at Least 1 Continuous AF (Atrial Fibrillation or Atrial Flutter) Episode ≥ 30 Minutes During the First 30 Days Post-surgery First 30 days following the initial ICU admission date after open-chest cardiac surgery. At least one episode of continuous AF (atrial fibrillation or atrial flutter) sustained ≥ 30 minutes documented by monitoring ECG measurements using ECG patches (ePatch) placed on the participant's chest.
Percentage of Participants With at Least 1 Continuous AF (Atrial Fibrillation or Atrial Flutter) Episode ≥ 4 Hours During the First 30 Days Post-surgery First 30 days following the initial ICU admission date after open-chest cardiac surgery. At least one episode of continuous AF (atrial fibrillation or atrial flutter) sustained ≥ 4 hours documented by monitoring ECG measurements using ECG patches (ePatch) placed on the participant's chest.
Percentage of Participants With at Least 1 Continuous Atrial Flutter Episode ≥ 30 Seconds During the First 30 Days Post-surgery First 30 days following the initial ICU admission date after open-chest cardiac surgery. At least one episode of continuous atrial flutter sustained ≥ 30 seconds documented by monitoring ECG measurements using ECG patches (ePatch) placed on the participant's chest.
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. At least one episode of continuous AF (atrial fibrillation or atrial flutter) sustained ≥ 5 minutes documented by monitoring ECG measurements using ECG patches (ePatch) placed on the participant's chest.
Percentage of Participants With at Least 1 Continuous AF (Atrial Fibrillation or Atrial Flutter) Episode ≥ 6 Minutes During the First 30 Days Post-surgery First 30 days following the initial ICU admission date after open-chest cardiac surgery. At least one episode of continuous AF (atrial fibrillation or atrial flutter) sustained ≥ 6 minutes documented by monitoring ECG measurements using ECG patches (ePatch) placed on the participant's chest.
Percentage of Participants With at Least 1 Continuous AF (Atrial Fibrillation or Atrial Flutter) Episode ≥ 1 Hour During the First 30 Days Post-surgery First 30 days following the initial ICU admission date after open-chest cardiac surgery. At least one episode of continuous AF (atrial fibrillation or atrial flutter) sustained ≥ 1 hour documented by monitoring ECG measurements using ECG patches (ePatch) placed on the participant's chest.
Percentage of Participants With at Least 1 Continuous Episode of Either Atrial Fibrillation or Atrial Flutter or Atrial Tachycardia ≥ 30 Seconds During the First 30 Days Post-surgery First 30 days following the initial ICU admission date after open-chest cardiac surgery. At least one episode of continuous atrial fibrillation or atrial flutter or atrial tachycardia sustained ≥ 30 seconds documented by monitoring ECG measurements using ECG patches (ePatch) placed on the participant's chest.
Percentage of Participants With at Least 1 Continuous Atrial Tachycardia Episode (Defined as the Duration of the Longest Supraventricular Tachycardia [SVT] Run) ≥ 30 Seconds During the First 30 Days Post-surgery First 30 days following the initial ICU admission date after open-chest cardiac surgery. At least one episode of continuous atrial tachycardia sustained ≥ 30 seconds documented by monitoring ECG measurements using ECG patches (ePatch) placed on the participant's chest.
Trial Locations
- Locations (32)
University of Maryland Medical Center /ID# 234352
🇺🇸Baltimore, Maryland, United States
Medizinische Universitaet Wien /ID# 238259
🇦🇹Vienna, Wien, Austria
Stanford University School of Med /ID# 236922
🇺🇸Stanford, California, United States
Lutheran Medical Group /ID# 237990
🇺🇸Fort Wayne, Indiana, United States
Icahn School of Medicine at Mount Sinai - The Mount Sinai Medical Center /ID# 234449
🇺🇸New York, New York, United States
Washington University-School of Medicine /ID# 238121
🇺🇸Saint Louis, Missouri, United States
East Carolina University /ID# 237820
🇺🇸Greenville, North Carolina, United States
Mission Hospital /ID# 237231
🇺🇸Asheville, North Carolina, United States
Toronto General Hospital /ID# 237680
🇨🇦Toronto, Ontario, Canada
Montreal Heart Insitute /ID# 234859
🇨🇦Montreal, Quebec, Canada
University of Virginia /ID# 237611
🇺🇸Charlottesville, Virginia, United States
University of Ottawa Heart Institute /ID# 236012
🇨🇦Ottawa, Ontario, Canada
ASST degli Spedali Civili di Brescia /ID# 234861
🇮🇹Brescia, Italy
Academisch Medisch Centrum /ID# 237113
🇳🇱Amsterdam, Netherlands
University Hospital Plymouth NHS Trust /ID# 234423
🇬🇧Plymouth, United Kingdom
Medstar Washington Hospital Center /ID# 234322
🇺🇸Washington, District of Columbia, United States
Dartmouth-Hitchcock Medical Center /ID# 237530
🇺🇸Lebanon, New Hampshire, United States
Ohio State University Medical Center /ID# 234408
🇺🇸Columbus, Ohio, United States
CIUSSS du Nord-de-l'ile-de-Montréal_Hopital du Sacré-Coeur de Montréal /ID# 234316
🇨🇦Montreal, Quebec, Canada
CHUM - Centre hospitalier de l'Universite de Montréal /ID# 238163
🇨🇦Montreal, Quebec, Canada
Asklepios Klinik Harburg-Hamburg /ID# 234855
🇩🇪Hamburg, Germany
Orebro University Hospital Sweden /ID# 236047
🇸🇪Orebro, Orebro Lan, Sweden
Hospital Clínic. University of Barcelona /ID# 234853
🇪🇸Barcelona, Spain
Institut universitaire de cardiologie et de pneumologie de Québec - Université L /ID# 237166
🇨🇦Québec, Quebec, Canada
Emory Saint Joseph's Hospital /ID# 234334
🇺🇸Atlanta, Georgia, United States
Baylor Scott & White Research Institute /ID# 235937
🇺🇸Plano, Texas, United States
Ochsner Medical Center /ID# 238004
🇺🇸New Orleans, Louisiana, United States
Yale New Haven Hospital - Yale School of Medicine /ID# 238221
🇺🇸New Haven, Connecticut, United States
University of Michigan /ID# 236228
🇺🇸Ann Arbor, Michigan, United States
Duke University Medical Center /ID# 234314
🇺🇸Durham, North Carolina, United States
Medical University of South Carolina /ID# 236476
🇺🇸Charleston, South Carolina, United States
University of Utah /ID# 237601
🇺🇸Salt Lake City, Utah, United States