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
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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 |
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 |

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:
Other: Placebo oral capsule Other Name: placebo |
- 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 ]
- 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 ]
- 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 ]
- 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 ]

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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 |
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

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

Principal Investigator: | Jonathan Piccini, MD | Duke University | |
Study Director: | Chris Dufton, PhD | ARCA Biopharma, Inc. |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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 |
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 |
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 |