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

This study is currently recruiting participants.
Verified April 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: April 1, 2014
Last verified: April 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 during the 24-week Follow-up Period with ventricular tachycardia (VT), ventricular fibrillation (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 heart failure (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 ]

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 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 Adverse Events/Serious Adverse Events over time [ 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 ]

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
  • New York Heart Association (NYHA) Class I-III
  • Recent onset of symptomatic persistent AF, 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.
  • Left ventricular internal diameter in diastole (LVIDD) ≥ 2.7 cm/m2 assessed ≤ 12 months prior to Visit 1
  • Clinical euvolemia at the time of randomization
  • Receiving appropriate anticoagulation therapy prior to randomization
  • Must either have a Medtronic implanted device that can measure atrial fibrillation burden (AFB), or agree to have one inserted as clinically indicated

Key Exclusion Criteria:

  • Use of any of the following ≤ 7 days of Visit 2: Amiodarone, disopyramide, dofetilide, dronedarone, encainide, flecainide, propafenone, sotalol, calcium channel blockers, theophylline, daily NSAIDS (e.g. ibuprofen, celecoxib), thiazolidinediones, or frequent use of nitroglycerin (i.e., > 6 sublingual tablets/week)
  • Chronic use (> 2 days/week) of an inhaled β2-selective adrenergic agonist ≤ 7 days of Visit 2
  • More than two previous ECV ≤ 12 months of Visit 1 or if the most recent ECV failed to produce SR
  • Evidence of paroxysmal AF during the Screening Period
  • 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 1 or at any time during the Screening Period
  • Evidence of an appropriate firing of an implanted cardioverter-defibrillator (ICD) device for ventricular tachycardia (VT) or ventricular fibrillation (VF) ≤ 90 days of Visit 2
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01970501

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

Locations
United States, Michigan
Sparrow Clinical Research Institute Recruiting
Lansing, Michigan, United States, 48912
Contact: Sandra Mitchell    517-364-5737    sandra.mitchell@sparrow.org   
Principal Investigator: John Ip, MD         
United States, Nebraska
Bryan Heart Recruiting
Lincoln, Nebraska, United States, 68506
Contact: Teresa Lassen    402-783-3275    teresa.lassen@bryanheart.com   
Principal Investigator: Steven Krueger, MD         
United States, Ohio
The Ohio State University Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Michelle Bright    614-292-3496    michelle.bright@osumc.edu   
Principal Investigator: Sitaramesh Emani, MD         
United States, Pennsylvania
Berks Cardiologists, Ltd. Recruiting
Wyomissing, Pennsylvania, United States, 19610
Contact: Sharon Leuchak    610-685-8500 ext 225    sleuchak@berkscardiologists.com   
Principal Investigator: Louis Borgatta, MD         
United States, Tennessee
The Jackson Clinic, PA Recruiting
Jackson, Tennessee, United States, 38305
Contact: Suzan Lasley    731-422-0307    slasley@jacksonclinic.com   
Principal Investigator: Joseph Okolo, MD         
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 1, 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
Atrial Flutter
Heart Failure
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 April 17, 2014