Abstract 12420: Orally Inhaled Flecainide for the Conversion of Recent-Onset, Symptomatic Atrial Fibrillation to Sinus Rhythm: Final Results From the Phase 2 Instant Trial

Abstract

Introduction: The INSTANT trial was a multicenter, open-label, single-arm study of flecainide acetate oral inhalation solution (FlecIH) for acute conversion of recent-onset, symptomatic atrial fibrillation (AF) to sinus rhythm (SR). The initial dose-ranging stage of the trial established safety and feasibility, while showing a dose- and concentration-dependent increase in efficacy (dose range: 30-120 mg); the highest dose was selected for this evaluation. Methods: Patients with symptomatic paroxysmal AF (≤ 48 hours) self-administered 120 mg FlecIH over 8 minutes in a monitored setting using a breath-actuated nebulizer and were continuously monitored for 90 minutes using a 12-lead Holter. Symptoms, vital signs and adverse events were recorded. Safety analyses included all patients who received 120 mg FlecIH (N=98). Efficacy analyses were performed on a modified intention to treat population (N=81) that excluded patients with systemic flecainide present prior to dosing with study drug. Results: The population had a mean age of 60.5 years, a mean BMI of 27.0 kg/m2 and 34.7% were female. All patients reported ≥1 AF-related symptoms at baseline and 87.8% presented with AF symptoms ≤ 24 hours in duration. The conversion rate was 46.9% (95% CI: 36.4%, 57.7%), with a median time of 13.7 minutes from the start of the inhalation. A greater proportion of patients were asymptomatic or had improved symptoms following conversion of AF to SR with inhaled flecainide compared to patients whose AF did not convert (92.1% and 45.4%, respectively, p < 0.001). Two patients had CV events that were considered serious (bradycardia and atrial flutter with 1:1 AV conduction). Both CV events were transient (12 and 6 minutes, respectively), required no treatment and resolved without sequelae. Median time to discharge was 2.5 hours for patients whose AF converted to SR with inhaled flecainide and by Day 5 none had experienced AF recurrence. In contrast, 35 (81.4%) patients in the no conversion group had undergone ECV by Day 5. Conclusions: The risk-benefit of orally inhaled flecainide acetate inhalation solution for acute cardioversion of recent onset AF appears favorable and may provide a safe, effective, and convenient first-line therapeutic option for AF conversion.