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

This study is ongoing, but not recruiting participants.

Sponsor:

ClinicalTrials.gov Identifier:

NCT01970501

First Posted: October 28, 2013

Last Update Posted: September 6, 2017

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

Collaborator:

Medtronic

Information provided by (Responsible Party):

ARCA Biopharma, Inc.

Tracking Information

First Submitted Date ^ICMJE

October 23, 2013

First Posted Date ^ICMJE

October 28, 2013

Last Update Posted Date

September 6, 2017

Start Date ^ICMJE

April 2014

Estimated Primary Completion Date

December 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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 ]

Original Primary Outcome Measures ^ICMJE

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 ]

Change History

Complete list of historical versions of study NCT01970501 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

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 ]
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 ]
Total number of hospitalization days per patient (all-cause) during the Total Study Period [ Time Frame: 4 years ]
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 ]
Proportion of patients with adequate ventricular rate control in the setting of AF/AFL [ Time Frame: 4 years ]

Original Secondary Outcome Measures ^ICMJE

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 ]
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 ]
Total number of hospitalization (all-cause) days per patient during the Total Study Period [ Time Frame: 4 years ]
Time to first event of ACM or HF hospitalization (as assessed by the Investigator) during the Total Study Period [ Time Frame: 4 years ]
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 ]

Current Other Outcome Measures ^ICMJE

Incidence of ACM during the Total Study Period [ Time Frame: 4 years ]
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 ]
Incidence of heart block during the Total Study Period [ Time Frame: 4 years ]
Incidence and severity of treatment-emergent Adverse Events/Serious Adverse Events over time during the Total Study Period [ Time Frame: 4 years ]
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 ]
Proportion of patients attaining target study drug dose during the Drug Titration Period [ Time Frame: end of treatment week 8 ]

Original Other Outcome Measures ^ICMJE

Incidence of ACM during the Total Study Period [ Time Frame: 4 years ]
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 ]
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 ]
Incidence and severity of treatment-emergent AEs/SAEs over time [ Time Frame: 4 years ]
Incidence of neoplasm-related AEs/SAEs [ Time Frame: 4 years ]
Change from baseline (randomization) over time on clinical laboratory tests, vital signs and weight [ Time Frame: 4 years ]
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 ]

Descriptive Information

Brief Title ^ICMJE

Genetically Targeted Therapy for the Prevention of Symptomatic Atrial Fibrillation in Patients With Heart Failure

Official Title ^ICMJE

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

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.

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 Type ^ICMJE

Interventional

Study Phase

Phase 2

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Condition ^ICMJE

Current or Recent History of Atrial Fibrillation

Intervention ^ICMJE

Drug: bucindolol hydrochloride
Other Name: bucindolol
Drug: metoprolol succinate
Other Names:
- Toprol-XL
- metoprolol

Study Arms

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

Publications *

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Active, not recruiting

Estimated Enrollment ^ICMJE

250

Estimated Completion Date

December 2017

Estimated Primary Completion Date

December 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Sex/Gender

Sexes Eligible for Study:

All

Ages

18 Years to 85 Years (Adult, Senior)

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

Canada, Hungary, Netherlands, Poland, Serbia, United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT01970501

Other Study ID Numbers ^ICMJE

BUC-CLIN-303

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Not Provided

IPD Sharing Statement

Plan to Share IPD:

Responsible Party

ARCA Biopharma, Inc.

Study Sponsor ^ICMJE

ARCA Biopharma, Inc.

Collaborators ^ICMJE

Medtronic

Investigators ^ICMJE

Principal Investigator:	Jonathan Piccini, MD	Duke University
Study Director:	Chris Dufton, PhD	ARCA Biopharma, Inc.

PRS Account

ARCA Biopharma, Inc.

Verification Date

September 2017

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

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