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 September 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: September 2, 2014
Last verified: September 2014
  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
Atrial Fibrillation
Atrial Flutter
Drug: bucindolol hydrochloride
Drug: metoprolol succinate
Phase 2
Phase 3

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 conversion to stable sinus rhythm (SR) [ 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 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. 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 ]

Estimated Enrollment: 620
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 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.

  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
  • 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
  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 23 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: September 2, 2014
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
Atrial Flutter
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Metoprolol
Metoprolol succinate
Bucindolol
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
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

ClinicalTrials.gov processed this record on September 16, 2014