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

AbbVie32 sites in 9 countries323 target enrollmentMarch 1, 2019

ConditionsPost-Operative Atrial Fibrillation

InterventionsAGN-151607 Placebo

DrugsAGN-151607 Placebo

Overview

Phase: Phase 2
Intervention: AGN-151607
Conditions: Post-Operative Atrial Fibrillation
Sponsor: AbbVie
Enrollment: 323
Locations: 32
Primary Endpoint: Percentage of Participants With at Least 1 Continuous AF (Atrial Fibrillation or Atrial Flutter) Episode ≥ 30 Seconds During the First 30 Days Post-surgery
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

March 1, 2019

End Date

March 6, 2023

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

AbbVie

Responsible Party

Sponsor

Eligibility Criteria

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
•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

Arms & Interventions

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.

Intervention: AGN-151607

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.

Intervention: AGN-151607

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: Placebo

Outcomes

Primary Outcomes

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

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.)
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 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.)
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.)
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 ≥ 6 Hours 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 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.)
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 ≥ 30 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 ≥ 4 Hours 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 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.)
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.)
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.)
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.)
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.)
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.)