Effect of Early Treatment with Fluvoxamine on Risk of Emergency Care and Hospitalization Among Patients with COVID-19: The TOGETHER Randomized Platform Clinical Trial
Notice bibliographique
Résumé
ABSTRACT Background Recent evidence indicates a potential therapeutic role of fluvoxamine for COVID-19. In the TOGETHER randomized platform clinical trial for acutely symptomatic patients with COVID-19, we assessed the efficacy of fluvoxamine vs. placebo in preventing either extended emergency room observation or hospitalization due to COVID-19. Herein, we report the preliminary findings. Methods This placebo-controlled, randomized, adaptive, platform trial conducted among symptomatic Brazilian adults confirmed positive for SARS-CoV-2 included eligible patients with a known risk factor for progression to severe disease. Patients were randomly assigned to either fluvoxamine (100 mg twice daily for 10 days) or placebo. The primary endpoint was a composite outcome of emergency room observation for >6 hours or hospitalization from COVID-19 up to 28 days post randomization using intention to treat. Modified intention to treat (mITT) explored patients receiving at least 24 hours of treatment before a primary outcome event. Secondary outcomes included viral clearance at day 7, time to hospitalization, mortality, and adverse drug reactions. We used a Bayesian analytic framework to determine effects along with probability of success of intervention compared to placebo. The trial is registered at clinicaltrials.gov ( NCT04727424 ) and is ongoing. Findings The study team screened 9020 potential participants for this trial. The trial was initiated on June 2, 2020, with the current protocol reporting randomization from January 15, 2021 to August 6 th 2021, when the trial arms were stopped for superiority. A total of 3238 patients were allocated to fluvoxamine (n=739), placebo (n=733) and other treatments (n=1766). Herein, we report the effectiveness of fluvoxamine vs. a concurrent placebo control. The average age of participants was 50 years (range 18-102 years); 57% were female. The proportion of patients observed in an emergency room for >6 hours or admitted to hospital due to COVID-19 was lower for the fluvoxamine group compared to placebo (77/739 vs 108/733; Relative Risk [RR]: 0.71; 95% Bayesian Credible Interval [95% BCI]: 0.54 - 0.93), with a probability of superiority of 99.4% surpassing the prespecified superiority threshold of 97.6% (risk difference 4.3%). Of the composite primary outcome events, 88% were hospitalizations. Findings were similar for the mITT analysis (RR0.68, 95% BCI : 0.50- 0.91). We found no significant relative effects between the fluvoxamine and placebo groups on viral clearance at day 7 (Odds ratio [OR]: 0.75; 95% Confidence Intervals [95% CI]: 0.53 - 1.07), mortality (OR: 0.70; 95% CI: 0.36 - 1.30), time to death (Hazard ratio [HR]: 0.79; 95% CI: 0.58 - 1.08), days hospitalized (Mean Difference (MD) 1.22 days; 95% CI: 0.98 - 1.53), number of days ventilated (MD 1.10; 95% CI: 0.70 - 1.73) or other secondary outcomes. Data capturing all 28 days of follow-up will be reported after August 26 th , 2021. Interpretation Treatment with fluvoxamine (100 mg twice daily for 10 days) among high-risk outpatients with early diagnosed COVID-19, reduced the need for extended emergency room observation or hospitalization. Funding The trial was supported by FastGrants and The Rainwater Foundation.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».