Genetically Targeted Therapy for the Prevention of Symptomatic Atrial Fibrillation in Patients With Heart Failure (GENETIC-AF)
Current or Recent History of Atrial Fibrillation
About this trial
This is an interventional treatment trial for Current or Recent History of Atrial Fibrillation focused on measuring 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
Eligibility Criteria
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
Sites / Locations
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Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
bucindolol hydrochloride
metoprolol succinate
bucindolol hydrochloride (bucindolol) Participants were randomized (1:1) to blinded treatment with bucindolol or metoprolol and titrated weekly to target doses of 50 mg twice daily (BID; < 75 kg) or 100 mg BID (≥ 75 kg) for bucindolol or 200 mg once daily (QD) for metoprolol. 84% of bucindolol participants attained target dose and 72% of metoprolol participants attained target dose. The lowest starting dose of bucindolol was 6.25 mg BID with weekly dose titrations to the weight-based target dose or to the maximum tolerated dose. The starting dose assigned was based on the patient's beta-blocker treatment prior to randomization. Capsules for titration were available in the following dosage strengths to be taken twice daily (with or without food): 6.25mg, 12.5mg, 25mg, 50mg, and 100mg.
metoprolol succinate (Toprol-XL) Participants were randomized (1:1) to blinded treatment with bucindolol or metoprolol and titrated weekly to target doses of 50 mg twice daily (BID; < 75 kg) or 100 mg BID (≥ 75 kg) for bucindolol or 200 mg once daily (QD) for metoprolol. 84% of bucindolol participants attained target dose and 72% of metoprolol participants attained target dose. The lowest starting dose of metoprolol was 25 mg QD with weekly dose titrations to the target dose or to the maximum tolerated dose. The starting dose assigned was based upon the patient's beta-blocker treatment prior to randomization. Capsules for titration were 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.