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Completed

NCT Number: NCT01970501

Genetically Targeted Therapy for the Prevention of Symptomatic Atrial Fibrillation in Patients With Heart Failure

This study is being done to compare the effects of bucindolol hydrochloride (bucindolol) to metoprolol succinate (Toprol-XL) on the recurrence of symptomatic atrial fibrillation/atrial flutter in patients with heart failure who have a specific genotype for the beta-1 adrenergic receptor.

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Key information

Conditions

Current or Recent History of Atrial Fibrillation Arrhythmias, Cardiac Atrial Fibrillation Atrial Flutter Cardiovascular Diseases Heart Diseases Heart Failure Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

ARCA Clinical Research Site #612, Calgary, Alberta, Canada

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About this study

The goal of the GENETIC-AF trial is to demonstrate the superiority of pharmacogenetically targeted bucindolol compared to metoprolol for the prevention of symptomatic atrial fibrillation or atrial flutter in a genotype-defined population with heart failure and/or reduced left ventricular ejection fraction at high risk of atrial fibrillation/atrial flutter recurrence.

Who can participate

Healthy volunteers accepted: No

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

Key Inclusion Criteria:

  • Must weigh at least 40 kg
  • Possess the β1389 Arg/Arg genotype
  • Left Ventricular Ejection Fraction (LVEF) < 0.50 assessed within 12 months prior to Screening
  • At least one episode of symptomatic paroxysmal or persistent AF within 180 days of Screening
  • Clinically appropriate for electrical cardioversion (ECV) if AF/AFL is present after study drug initiation
  • Receiving appropriate anticoagulation therapy prior to Randomization

Key Exclusion Criteria:

  • NYHA Class IV symptoms at the time of Randomization
  • Significant fluid overload at Randomization
  • Permanent AF at Screening
  • More than two previous ECV within 6 months of Randomization or if the most recent ECV failed to produce SR
  • Presence of an LVAD, or likely to requirement LVAD placement within 6 months of Randomization
  • History of a successful atrioventricular (AV) node ablation
  • History of an AF/AFL ablation within 30 days of Randomization
  • Evidence of an appropriate firing of an implanted cardioverter-defibrillator (ICD) device for ventricular tachycardia (VT) or ventricular fibrillation (VF) within 90 days of Randomization

Treatment and study plan

bucindolol hydrochloride

Drug

Other names: bucindolol

Metoprolol succinate

Drug

Other names: Toprol-XL, metoprolol

Placebo oral capsule

Other

Other names: placebo

Primary outcomes

  1. Time to First Event of Symptomatic Atrial Fibrillation/Atrial Flutter (AF/AFL) or All Cause Mortality (ACM) During the 24-week Follow-up Period After Establishment of Stable Sinus Rhythm (SR) on Study Drug [End of Treatment Week 24].

    Time frame: end of treatment week 24

    Time-to-event is calculated as the date of the event minus the date of initiation of efficacy follow-up, with 1 added in order to include both the start date and end date of the interval. Cox's proportional hazards model will be used to calculate estimated hazard ratios and 95% confidence intervals. The calculations will be performed with the SAS PHREG procedure, with the stratification variables specified in the STRATA statement and the treatment group comparator and any covariates being examined specified in the MODEL statement. For the primary endpoint, the appropriateness of assuming proportional hazards will be explored by the graphing of log (-log(survival function)) over follow-up for each treatment group.

Secondary outcomes

  1. Time to First Event of Symptomatic or Asymptomatic AF/AFL or ACM During the 24-week Follow-up Period After Establishment of Stable SR on Study Drug [End of Treatment Week 24]

    Time frame: end of treatment week 24

    Number of days on study medication before participant experienced symptomatic or asymptomatic atrial fibrillation, atrial flutter, or all-cause mortality during the 24 week follow up period.

  2. Number of Patients With Adequate Ventricular Rate Control During the 24-week Follow-up Period

    Time frame: end of treatment week 24

    Number of patients with adequate ventricular rate control following the start of medication during the 24-week Follow-up Period

  3. Total Number of Hospitalization Days Per Patient (All-cause) During the Total Study Period (24 Weeks)

    Time frame: 24 weeks

    Total number of hospitalization days per patient (all-cause) following the start of study medication during the Total Study Period (24 weeks). Hospitalization was defined by a hospital admission (note that same day admit and discharge equates to 0 days duration), ER visits were not counted as events.

Sponsors and collaborators

Lead sponsor

ARCA Biopharma, Inc.

Industry

Collaborators

  • Medtronic

Registry information

Official study title

GENETIC-AF - A Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Toprol-XL for Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients With Heart Failure

Acronym: GENETIC-AF

Important dates

Study start
2014
Primary completion
2017
Study completion
2017
First posted
Oct 28, 2013
Registry last updated
Sep 26, 2022

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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