1 november 2021: Bron Nature

Fluvoxamine, een goedkoop, algemeen verkrijgbaar medicijn (anti-depressiva), vermindert zowel het risico op overlijden (90 procent) door COVID-19 als de noodzaak voor mensen met de ziekte om intensieve medische zorg te krijgen (65 procent). Dat blijkt uit een gerandomiseerde placebo gecontroleerde Braziliaanse studie bij totaal 1.497 mensen die COVID-19 hadden en een hoog risico liepen op een ernstige ziekte. Ongeveer de helft kreeg fluvoxamine (N = 741) en de rest kreeg een placebo (N = 756).

Het medicijn, Fluvoxamine, wordt gebruikt voor aandoeningen zoals depressie en obsessief-compulsieve stoornis. Maar het is ook bekend dat het immuunreacties dempt en weefselbeschadiging tempert. Onder de deelnemers aan de studie die het medicijn namen zoals voorgeschreven en dat deden in de vroege stadia van de ziekte, daalde het aantal COVID-19-gerelateerde sterfgevallen met ongeveer 90% en de behoefte aan intensieve COVID-19-gerelateerde medische zorg daalde met ongeveer 65%.

Het volledige studieverslag is gepubliceerd in The Lancet. Klik op de titel van het abstract:

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

Open AccessPublished:October 27, 2021DOI:https://doi.org/10.1016/S2214-109X(21)00448-4


Summary

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 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 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.

Funding

FastGrants and The Rainwater Charitable Foundation.

Translation

For the Portuguese translation of the abstract see Supplementary Materials section.




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Figures

  • Figure thumbnail gr1
    Figure 1Trial profile
  • Figure thumbnail gr2
    Figure 2Probability of efficacy and Bayesian relative risk of hospitalisation defined as either retention in a COVID-19 emergency setting or transfer to tertiary hospital due to COVID-19 for fluvoxamine versus placebo
  • Figure thumbnail gr3
    Figure 3Subgroup analyses of fluvoxamine versus placebo in the TOGETHER Trial

Tables

Linked Articles


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