AIMS: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia. New treatments are needed to cardiovert recent-onset paroxysmal AF quickly and safely. RESTORE-1 was a multicentre, randomized, double-blind, placebo-controlled trial of a 120 mg orally inhaled solution of flecainide acetate (FlecIH-103) for cardioversion of symptomatic, recent-onset (≤48 h) paroxysmal AF. The study aim was to evaluate the efficacy and safety of FlecIH-103 administered via oral inhalation. METHODS AND RESULTS: Patients experiencing a recent-onset paroxysmal AF episode were randomized to receive a single dose of FlecIH-103 or placebo delivered over two 3.5 min inhalation periods, while patients were monitored using 12-lead electrocardiograms and Holter. The trial was stopped prematurely after treating 55 patients, due to lower-than-expected conversion rates and plasma levels. Mean age was 59.6 years, 31.5% of patients were female, and 59.2% were having their first AF episode. Conversion rate was 30.8% (95% confidence interval: 14.7-43.8) for the active group (n = 39) and 0.0% for the placebo group (n = 12) (P = 0.04). Median time to conversion was 12.8 min (IQR: 17.2). In the active group, the mean flecainide plasma level was 198 ng/mL (SD: 156), which is ∼50% lower than in the previous studies. The most common adverse events (AEs) were dysgeusia, dyspnoea, and cough. All AEs were short-lasting and of mild or moderate intensity. CONCLUSION: Despite early termination of the trial, FlecIH-103 was significantly more effective than placebo in cardioverting AF. Safety data did not show any serious AEs. Further studies of FlecIH-103 are needed to optimize the combination of drug formulation and inhalation delivery platform. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov, unique identifier: NCT05039359.

• Klíčová slova
• Atrial fibrillation, Cardioversion, Flecainide, Oral inhalation,
• MeSH
• antiarytmika * aplikace a dávkování   škodlivé účinky   MeSH
• aplikace inhalační MeSH
• časové faktory MeSH
• dvojitá slepá metoda MeSH
• elektrokardiografie ambulantní MeSH
• fibrilace síní * farmakoterapie   diagnóza   patofyziologie   MeSH
• flekainid * aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• předčasné ukončení klinických zkoušek MeSH
• senioři MeSH
• srdeční frekvence * účinky léků   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antiarytmika * MeSH
• flekainid * MeSH