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 April 2015 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: April 6, 2015
Last verified: April 2015
  Purpose

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 Intervention Phase
Current or Recent History of Atrial Fibrillation
Drug: bucindolol hydrochloride
Drug: metoprolol succinate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by ARCA Biopharma, Inc.:

Primary Outcome Measures:
  • 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 [ Time Frame: end of treatment week 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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/AFL on ECG at the end of study who demonstrate ventricular response rate (VRR) control [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • 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 [ 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, quantitative ECG parameters [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  • Proportion of patients attaining target study drug dose during the Drug Titration Period [ Time Frame: end of treatment week 8 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 200
Study Start Date: April 2014
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 to maintain blinded dosing.

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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Must weigh ≥ 40 kg
  • Possess the β1389 Arg/Arg genotype
  • Left Ventricular Ejection Fraction (LVEF) < 0.50 assessed ≤ 12 months prior to Screening
  • At least one episode of symptomatic paroxysmal or persistent AF within ≤ 120 days of Screening
  • Clinically appropriate for electrical cardioversion (ECV) if AF/AFL is present 3 weeks after study drug initiation
  • Clinical euvolemia at the time of Randomization
  • Receiving appropriate anticoagulation therapy prior to Randomization

Key Exclusion Criteria:

  • NYHA Class IV symptoms at the time of Randomization
  • Permanent AF at Screening
  • More than two previous ECV ≤ 12 months of Screening or if the most recent ECV failed to produce SR
  • History of a successful atrioventricular (AV) node ablation
  • History of an AF 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01970501

Contacts
Contact: Jennifer Meriwether 720-940-2132 jennifer.meriwether@arcabiopharma.com

  Show 39 Study Locations
Sponsors and Collaborators
ARCA Biopharma, Inc.
Medtronic
Investigators
Principal Investigator: Jonathan Piccini, MD Duke University
Study Director: Chris Dufton, PhD ARCA Biopharma, Inc.
  More Information

Publications:

Responsible Party: ARCA Biopharma, Inc.
ClinicalTrials.gov Identifier: NCT01970501     History of Changes
Other Study ID Numbers: BUC-CLIN-303
Study First Received: October 23, 2013
Last Updated: April 6, 2015
Health Authority: United States: Food and Drug Administration

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:
Atrial Fibrillation
Heart Failure
Arrhythmias, Cardiac
Cardiovascular Diseases
Heart Diseases
Pathologic Processes
Bucindolol
Metoprolol
Metoprolol succinate
Adrenergic Agents
Adrenergic Antagonists
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Anti-Arrhythmia Agents
Antihypertensive Agents
Autonomic Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sympatholytics
Sympathomimetics
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on April 30, 2015