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Genetically Targeted Therapy for the Prevention of Symptomatic Atrial Fibrillation in Patients With Heart Failure (GENETIC-AF)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by ARCA Biopharma, Inc.
Sponsor:
Collaborator:
Medtronic
Information provided by (Responsible Party):
ARCA Biopharma, Inc.
ClinicalTrials.gov Identifier:
NCT01970501
First received: October 23, 2013
Last updated: November 3, 2014
Last verified: November 2014

October 23, 2013
November 3, 2014
April 2014
December 2017   (final data collection date for primary outcome measure)
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 conversion to stable sinus rhythm (SR) [ Time Frame: end of treatment week 24 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01970501 on ClinicalTrials.gov Archive Site
  • Time to first event of AF/AFL (i.e., symptomatic or asymptomatic) or ACM during the 24-week Follow-up Period [ Time Frame: end of treatment week 24 ] [ Designated as safety issue: No ]
  • Proportion of patients with ventricular tachycardia (VT), ventricular fibrillation (VF), or symptomatic supraventricular tachycardia (SVT) during the 24-week Follow-up Period [ Time Frame: end of treatment week 24 ] [ Designated as safety issue: No ]
  • Total number of hospitalization days per patient (all-cause) during the Total Study Period [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Time to first event of AF/AFL (i.e., symptomatic or asymptomatic), heart failure (HF) hospitalization (as assessed by the Investigator), or ACM during the Total Study Period [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Proportion of patients who have AF on ECG at the end of study who demonstrate ventricular response rate (VRR) control [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Time to first event of AF/AFL (i.e., symptomatic or asymptomatic) or ACM during the 24-week Follow-up Period [ Time Frame: end of treatment week 24 ] [ Designated as safety issue: No ]
  • Proportion of patients during the 24-week Follow-up Period with VT, VF, or symptomatic supraventricular tachycardia (SVT) [ Time Frame: end of treatment week 24 ] [ Designated as safety issue: No ]
  • Total number of hospitalization (all-cause) days per patient during the Total Study Period [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Time to first event of ACM or HF hospitalization (as assessed by the Investigator) during the Total Study Period [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Proportion of patients who have AF on ECG at the end of the study who demonstrate ventricular response rate (VRR) control [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • Incidence of ACM during the Total Study Period [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  • Incidence of ACM, cardiovascular-related hospitalization (as assessed by the Investigator), or withdrawal of study drug due to an adverse event (AE) during the Drug Titration Period [ Time Frame: end of treatment week 8 ] [ Designated as safety issue: Yes ]
  • Incidence of heart block during the Total Study Period. Defined as third degree heart block, second degree heart block requiring pacemaker implantation, or symptomatic second degree heart block as determined by the Clinical Events Committee. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  • Incidence and severity of treatment-emergent Adverse Events/Serious Adverse Events over time during the Total Study Period [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  • Change from baseline (Visit 2) over time during the Total Study Period on: clinical laboratory tests, vital signs and weight [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  • Proportion of patients attaining target study drug dose during the Drug Titration Period. Supportive analyses will also be performed for the subpopulations receiving and not receiving previous beta blocker therapy at randomization. [ Time Frame: end of treatment week 8 ] [ Designated as safety issue: Yes ]
  • Incidence of ACM during the Total Study Period [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  • Incidence of ACM, cardiovascular-related hospitalization (as assessed by the Investigator), or withdrawal of study drug due to an adverse event (AE) during the Drug Titration Period [ Time Frame: end of treatment week 8 ] [ Designated as safety issue: Yes ]
  • Incidence during the Total Study Period of third degree heart block, second degree heart block requiring pacemaker implantation, or symptomatic second degree heart block as determined by the Clinical Events Committee [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  • Incidence and severity of treatment-emergent AEs/SAEs over time [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  • Incidence of neoplasm-related AEs/SAEs [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  • Change from baseline (randomization) over time on clinical laboratory tests, vital signs and weight [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  • Proportion of patients attaining target study drug dose for the subpopulations receiving and not receiving previous beta blocker therapy at randomization [ Time Frame: end of treatment week 8 ] [ Designated as safety issue: Yes ]
 
Genetically Targeted Therapy for the Prevention of Symptomatic Atrial Fibrillation in Patients With Heart Failure
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

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.

The goal of the GENETIC-AF trial is to demonstrate the superiority of pharmacogenetically targeted bucindolol compared to Toprol-XL 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 that has persistent symptomatic AF requiring electrical conversion to sinus rhythm.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Atrial Fibrillation
  • Atrial Flutter
  • Drug: bucindolol hydrochloride
    Other Name: bucindolol
  • Drug: metoprolol succinate
    Other Names:
    • Toprol-XL
    • metoprolol
  • Experimental: bucindolol hydrochloride

    bucindolol hydrochloride (bucindolol)

    Capsules are available in the following dosage strengths to be taken twice daily (with or without food): 6.25mg, 12.5mg, 25mg, 50mg, and 100mg.

    Intervention: Drug: bucindolol hydrochloride
  • Active Comparator: metoprolol succinate

    metoprolol succinate (Toprol-XL)

    Capsules are available in the following dosage strengths to be taken twice daily (with or without food): 25mg, 50mg, 100mg, 200mg and/or matching placebo to maintain blinded dosing.

    Intervention: Drug: metoprolol succinate

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
620
December 2017
December 2017   (final data collection date for primary outcome measure)

Key Inclusion Criteria:

  • Must weigh ≥ 40 kg
  • Symptomatic heart failure within 90 days of Visit 1
  • Symptomatic AF at Visit 1 and Visit 2, determined by the Investigator to require electrical cardioversion (ECV)
  • Possess the β1389Arg/Arg genotype
  • Left Ventricular Ejection Fraction (LVEF) < 0.50 assessed ≤ 12 months prior to Visit 1
  • Clinical euvolemia at the time of randomization
  • Receiving appropriate anticoagulation therapy prior to randomization

Key Exclusion Criteria:

  • Use of any of the following ≤ 7 days of Visit 2: amiodarone, disopyramide, dofetilide, dronedarone, flecainide, propafenone, sotalol, non-dihydropyridine calcium channel blockers, daily NSAIDS (e.g. ibuprofen, celecoxib), thiazolidinediones, or frequent use of nitroglycerin (i.e., > 6 sublingual tablets/week)
  • More than two previous ECV ≤ 12 months of Visit 1 or if the most recent ECV failed to produce SR
  • NYHA Class IV symptoms at Visit 1
  • Permanent AF at Visit 1
  • History of a successful atrioventricular (AV) node ablation
  • History of an AF ablation within 3 months of Visit 1
  • Myocardial infarction, unstable angina, acute coronary syndrome, cardiac surgery (including percutaneous transluminal coronary angioplasty or stent placement), or evidence of new ischemic changes as assessed by ECG within 90 days of Visit 2
  • Evidence of an appropriate firing of an implanted cardioverter-defibrillator (ICD) device for ventricular tachycardia (VT) or ventricular fibrillation (VF) within 90 days of Visit 2
Both
18 Years and older
No
Contact: Jennifer Meriwether 720-940-2132 jennifer.meriwether@arcabiopharma.com
United States
 
NCT01970501
BUC-CLIN-303
Yes
ARCA Biopharma, Inc.
ARCA Biopharma, Inc.
Medtronic
Principal Investigator: Jonathan Piccini, MD Duke University
Study Director: Chris Dufton, PhD ARCA Biopharma, Inc.
ARCA Biopharma, Inc.
November 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP