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

BACKGROUND: The optimal treatment for fetal supraventricular tachycardia (SVT) with 1:1 atrioventricular relationship is unclear. OBJECTIVE: We compared the effectiveness of transplacental treatment protocols used in 2 centers. METHODS: Pharmacologic treatment was used in 84 fetuses. Maternal oral flecainide was the primary therapy in center 1 (n = 34) and intravenous maternal digoxin in center 2 (n = 50). SVT mechanism was classified by mechanical ventriculoatrial (VA) time intervals as short VA or long VA. Treatment success was defined as conversion to sinus rhythm (SR), or rate control, defined as >15% rate reduction. RESULTS: Short VA interval occurred in 67 fetuses (80%) and long VA in 17 (20%). Hydrops was present 28 of 84 (33%). For short VA SVT, conversion to SR was 29 of 42 (69%) for digoxin and 24 of 25 (96%) for flecainide (P = .01). For long VA SVT, conversion to SR and rate control was 4 of 8 (50%) and 0 of 8, respectively, for digoxin, and 6 of 9 (67%) and 2 of 9 (cumulative 89%) for flecainide (P = .13). In nonhydropic fetuses, digoxin was successful in 23 of 29 (79%) and flecainide in 26 of 27 (96%) (P = .10). In hydrops, digoxin was successful in 8 of 21 (38%), flecainide alone in 6 of 7 (86%, P = .07 vs digoxin), and flecainide ± amiodarone in 7 of 7 (100%) (P = .01). Intrauterine or neonatal death occurred in 9 of 21 hydropic fetuses treated with digoxin (43%), compared to 0 of 7 (P = .06) treated with flecainide. CONCLUSIONS: Flecainide was more effective than digoxin, especially when hydrops was present. No adverse fetal outcomes were attributed to flecainide.

• Klíčová slova
• Fetal supraventricular tachycardia, Fetal ultrasound, Prenatal treatment,
• MeSH
• antiarytmika aplikace a dávkování   krev   MeSH
• aplikace orální MeSH
• digoxin aplikace a dávkování   krev   MeSH
• dospělí MeSH
• echokardiografie MeSH
• edém komplikace   MeSH
• flekainid aplikace a dávkování   krev   MeSH
• intravenózní podání MeSH
• klinické protokoly MeSH
• lidé MeSH
• mladý dospělý MeSH
• nemoci plodu diagnostické zobrazování   farmakoterapie   MeSH
• retrospektivní studie MeSH
• supraventrikulární tachykardie klasifikace   komplikace   diagnostické zobrazování   farmakoterapie   MeSH
• těhotenství MeSH
• terapie plodu metody   MeSH
• ultrasonografie prenatální MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• antiarytmika MeSH
• digoxin MeSH
• flekainid MeSH