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Completed

NCT Number: NCT03779841

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

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.

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Key information

Conditions

Post-operative Atrial Fibrillation

Age range

55 year–90 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Medizinische Universitaet Wien /ID# 238259, Vienna, State of Vienna, Austria

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

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.

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

    Time frame: 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 outcomes

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

  6. Percentage of Participants With at Least 1 Continuous AF (Atrial Fibrillation or Atrial Flutter) Episode ≥ 6 Minutes During the First 30 Days Post-surgery

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

  9. Percentage of Participants With at Least 1 Continuous AF (Atrial Fibrillation or Atrial Flutter) Episode ≥ 4 Hours During the First 30 Days Post-surgery

    Time frame: 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.

  10. Percentage of Participants With at Least 1 Continuous AF (Atrial Fibrillation or Atrial Flutter) Episode ≥ 6 Hours During the First 30 Days Post-surgery

    Time frame: 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.

  11. Percentage of Participants With at Least 1 Continuous AF (Atrial Fibrillation or Atrial Flutter) Episode ≥ 12 Hours During the First 30 Days Post-surgery

    Time frame: 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.

  12. Percentage of Participants With at Least 1 Continuous AF (Atrial Fibrillation or Atrial Flutter) Episode ≥ 24 Hours During the First 30 Days Post-surgery

    Time frame: 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.

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

    Time frame: 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.

  14. Percentage of Participants With at Least 1 Continuous Atrial Flutter Episode ≥ 30 Seconds During the First 30 Days Post-surgery

    Time frame: 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.

  15. 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

    Time frame: 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.

  16. 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

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

AbbVie

Industry

Registry information

Official study 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

Important dates

Study start
2019
Primary completion
2022
Study completion
2023
First posted
Dec 19, 2018
Registry last updated
May 14, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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