מחקר קליני בחן את יכולתה של פלובוקסאמין להפחית את מספר הביקורים בחדר מיון ואשפוזים בחולי קורונה בסיכון גבוה.

ממצאים עיקריים

מחקר ברזילאי בחן מבוגרים לא מחוסנים שהציגו תסמיני קורונה והיו בסיכון גבוה להתפתחות המחלה.

המחקר תוכנן כדי לקבוע את יכולתה של פלובוקסאמין בהפחתת מספר הביקורים בחדר המיון ומשכם, וכן צורך באשפוז.

741 חולים הוקצו לטיפול בפלובוקסאמין, ו-756 לנטילת פלצבו.

המטופלים טופלו בביתם, וקיבלו או פלובוקסאמין (100 מ"ג, פעמיים ביום למשך 10 ימים), או פלצבו, או טיפולים אחרים.

חולי קורונה מוקדמת בסיכון גבוה שנטלו פלובוקסאמין (100 מ"ג, פעמיים ביום למשך 10 ימים), הציגו צורך מופחת בביקורים בחדר המיון, בהשגחות ארוכות או באשפוז.

The Lancet Global Health

Publication Date: אוקטובר 27, 2021
Peer Reviewed: Yes
Publication Type: Original | Clinical Prospective
DOI: https://www.doi.org/10.1016/S2214-109X(21)00448-4

Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial

Gilmar Reis, Eduardo Augusto dos Santos Moreira-Silva, Daniela Carla Medeiros Silva, Lehana Thabane, Aline Cruz Milagres, Thiago Santiago Ferreira, Castilho Vitor Quirino dos Santos, Vitoria Helena de Souza Campos, Ana Maria Ribeiro Nogueira, Ana Paula Figueiredo Guimaraes de Almeida, Eduardo Diniz Callegari, Adhemar Dias de Figueiredo Neto, Leonardo Cançado Monteiro Savassi, Maria Izabel Campos Simplicio, Luciene Barra Ribeiro, Rosemary Oliveira, Ofir Harari, Jamie I Forrest, Hinda Ruton, Sheila Sprague, Paula McKay, Alla V Glushchenko, Craig R Rayner, Eric J Lenze, Angela M Reiersen, Gordon H Guyatt, Edward J Mills

Abstract

Background
Recent evidence indicates a potential therapeutic role of fluvoxamine for COVID-19. In the TOGETHER trial for acutely symptomatic patients with COVID-19, we aimed to assess the efficacy of fluvoxamine versus placebo in preventing hospitalisation defined as either retention in a COVID-19 emergency setting or transfer to a tertiary hospital due to COVID-19.

Methods
This placebo-controlled, randomised, adaptive platform trial done among high-risk symptomatic Brazilian adults confirmed positive for SARS-CoV-2 included eligible patients from 11 clinical sites in Brazil with a known risk factor for progression to severe disease. Patients were randomly assigned (1:1) to either fluvoxamine (100 mg twice daily for 10 days) or placebo (or other treatment groups not reported here). The trial team, site staff, and patients were masked to treatment allocation. Our primary outcome was a composite endpoint of hospitalisation defined as either retention in a COVID-19 emergency setting or transfer to tertiary hospital due to COVID-19 up to 28 days post-random assignment on the basis of intention to treat. Modified intention to treat explored patients receiving at least 24 h of treatment before a primary outcome event and per-protocol analysis explored patients with a high level adherence (>80%). We used a Bayesian analytic framework to establish the effects along with probability of success of intervention compared with placebo. The trial is registered at ClinicalTrials.gov (NCT04727424) and is ongoing.

Findings
The study team screened 9803 potential participants for this trial. The trial was initiated on June 2, 2020, with the current protocol reporting randomisation to fluvoxamine from Jan 20 to Aug 5, 2021, when the trial arms were stopped for superiority. 741 patients were allocated to fluvoxamine and 756 to placebo. The average age of participants was 50 years (range 18–102 years); 58% were female. The proportion of patients observed in a COVID-19 emergency setting for more than 6 h or transferred to a teritary hospital due to COVID-19 was lower for the fluvoxamine group compared with placebo (79 [11%] of 741 vs 119 [16%] of 756); relative risk [RR] 0·68; 95% Bayesian credible interval [95% BCI]: 0·52–0·88), with a probability of superiority of 99·8% surpassing the prespecified superiority threshold of 97·6% (risk difference 5·0%). Of the composite primary outcome events, 87% were hospitalisations. Findings for the primary outcome were similar for the modified intention-to-treat analysis (RR 0·69, 95% BCI 0·53–0·90) and larger in the per-protocol analysis (RR 0·34, 95% BCI, 0·21–0·54). There were 17 deaths in the fluvoxamine group and 25 deaths in the placebo group in the primary intention-to-treat analysis (odds ratio [OR] 0·68, 95% CI: 0·36–1·27). There was one death in the fluvoxamine group and 12 in the placebo group for the per-protocol population (OR 0·09; 95% CI 0·01–0·47). We found no significant differences in number of treatment emergent adverse events among patients in the fluvoxamine and placebo groups.

Interpretation
Treatment with fluvoxamine (100 mg twice daily for 10 days) among high-risk outpatients with early diagnosed COVID-19 reduced the need for hospitalisation defined as retention in a COVID-19 emergency setting or transfer to a tertiary hospital.