{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:40:38Z","timestamp":1779928838889,"version":"3.53.1"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T00:00:00Z","timestamp":1742860800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"InCarda Therapeutics Inc"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>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\u2005mg orally inhaled solution of flecainide acetate (FlecIH-103) for cardioversion of symptomatic, recent-onset (\u226448\u2005h) paroxysmal AF. The study aim was to evaluate the efficacy and safety of FlecIH-103 administered via oral inhalation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>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\u2005min 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\u201343.8) 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\u2005min (IQR: 17.2). In the active group, the mean flecainide plasma level was 198\u2005ng\/mL (SD: 156), which is \u223c50% 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical trial registration<\/jats:title>\n                  <jats:p>URL: https:\/\/clinicaltrials.gov, unique identifier: NCT05039359<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/europace\/euaf064","type":"journal-article","created":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T10:03:06Z","timestamp":1744452186000},"source":"Crossref","is-referenced-by-count":5,"title":["Flecainide acetate inhalation solution for cardioversion of recent-onset, symptomatic atrial fibrillation: results of the phase 3 RESTORE-1 trial"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2581-070X","authenticated-orcid":false,"given":"Michiel","family":"Rienstra","sequence":"first","affiliation":[{"name":"Department of Cardiology, University 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