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

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ClinicalTrials.gov Identifier: NCT01970501
Recruitment Status : Completed
First Posted : October 28, 2013
Last Update Posted : December 3, 2018
Sponsor:
Collaborator:
Medtronic
Information provided by (Responsible Party):
ARCA Biopharma, Inc.

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Current or Recent History of Atrial Fibrillation Drug: bucindolol hydrochloride Drug: metoprolol succinate Other: Placebo oral capsule Phase 2

Detailed Description:
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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 267 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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
Study Start Date : April 2014
Actual Primary Completion Date : December 28, 2017
Actual Study Completion Date : December 28, 2017

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Arms and Interventions
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Arm Intervention/treatment
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.

 Drug: bucindolol hydrochloride
Other Name: bucindolol
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 oral capsule to maintain blinded dosing.

 Drug: metoprolol succinate
Other Names:
  • Toprol-XL
  • metoprolol

Other: Placebo oral capsule
Other Name: placebo


Outcome Measures
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Primary Outcome Measures :
  1. Time to first event of symptomatic or asymptomatic 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 ]

Secondary Outcome Measures :
  1. Time to first event of symptomatic 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 ]
  2. 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 ]
  3. Total number of hospitalization days per patient (all-cause) during the Total Study Period [ Time Frame: 4 years ]
  4. 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 ]
  5. Proportion of patients with adequate ventricular rate control in the setting of AF/AFL [ Time Frame: 4 years ]

Other Outcome Measures:
  1. Incidence of ACM during the Total Study Period [ Time Frame: 4 years ]
  2. 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 ]
  3. Incidence of heart block during the Total Study Period [ Time Frame: 4 years ]
  4. Incidence and severity of treatment-emergent Adverse Events/Serious Adverse Events over time during the Total Study Period [ Time Frame: 4 years ]
  5. Change from baseline (Visit 2) over time during the Total Study Period on: clinical laboratory tests, vital signs and weight, quantitative ECG parameters [ Time Frame: 4 years ]
  6. Proportion of patients attaining target study drug dose during the Drug Titration Period [ Time Frame: end of treatment week 8 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01970501


Locations
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Sponsors and Collaborators
ARCA Biopharma, Inc.
Medtronic
Investigators
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Principal Investigator: Jonathan Piccini, MD Duke University
Study Director: Chris Dufton, PhD ARCA Biopharma, Inc.
More Information
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Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: ARCA Biopharma, Inc.
ClinicalTrials.gov Identifier: NCT01970501    
Other Study ID Numbers: BUC-CLIN-303
First Posted: October 28, 2013    Key Record Dates
Last Update Posted: December 3, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by ARCA Biopharma, Inc.:
atrial fibrillation
atrial flutter
heart failure
reduced left ventricle ejection fraction
electrical cardioversion
GENETIC-AF
Medtronic
 bucindolol
pharmacogenetic
ARCA
Toprol
Toprol-XL
Metoprolol
Metoprolol succinate
Additional relevant MeSH terms:
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Heart Failure
Atrial Fibrillation
Atrial Flutter
Heart Diseases
Cardiovascular Diseases
Arrhythmias, Cardiac
Pathologic Processes
Metoprolol
Bucindolol
Anti-Arrhythmia Agents
Antihypertensive Agents
Sympatholytics
Autonomic Agents
 Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Sympathomimetics
Vasodilator Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists