October 27, 2021

expert reaction to study looking at fluvoxamine as a COVID-19 treatment in high-risk outpatients with early-diagnosed COVID-19

A study from the TOGETHER trial published in the Lancet Global Health looks at the effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19.

Prof Penny Ward, Independent Pharmaceutical Physician, Visiting Professor in Pharmaceutical Medicine at King’s College London, said:

“This paper documents the outcomes from an ongoing adaptive ‘platform’ trial investigating the impact of treatments given early post symptom onset to COVID patients within the community.

“The trial is large and managed by a consortium of investigators in Brazil, Canada and the USA.  Limitations of the study design include non inclusion of cases of breakthrough disease post vaccination and the use of a ‘surrogate’ outcome (need for medical observation for COVID symptoms exceeding 6 hours) as the part of the composite primary outcome (either need for medical observation for COVID symptoms exceeding 6 hours or hospitalisation) rather than by combining major outcomes – hospitalisation, ICU admission or death – for the analysis.

“Fluvoxamine was identified as a possible treatment for covid based on its effects on endoreticular trafficking of viruses (i.e. potential antiviral) and impact on platelet function (reducing potential for inflammation and the severe coagulopathy noted in severe cases).  The population recruited were required to have at least one factor for more severe disease and to start treatment (fluvoxamine 100mg twice daily, or matching placebo)within 7 days of symptom onset.  The proportion of patients meeting the composite endpoint was significantly lower among the fluvoxamine recipients than in the placebo group (~10% vs ~15%) but this was mainly driven by the number of patients needing 6 hours of medical observation rather than those needing to be admitted for hospital treatment.

“Accordingly, while promising, particularly as this product is inexpensive and could be made widely available, the impact on more severe outcomes remains uncertain.  In addition, given the level of protection against severe disease offered by vaccination, the potential additional benefit of this agent in alleviating breakthrough infection and illness is uncertain as vaccinated patients were excluded from the trial.  In addition, although the study was intended to include high risk patients, the study demographics demonstrating an excess of females and patients aged <50 years of age, suggests that the population does not necessarily reflect a population at very high risk of hospitalisation/death from COVID for whom community intervention is most likely to be beneficial.

“Going forward, the inclusion of patients with vaccine breakthrough infection in trials of community based interventions will be important, and trial protocols should be amended to enable inclusion of this important subgroup with appropriate pre-treatment stratification and sample size adjustment to enable meaningful conclusions to be reached.”

‘Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial’ by Gilmar Reis et al. was published in The Lancet Global Health at 23:30 UK time on Wednesday 27 October 2021.

DOI: 10.1016/S2214-109X(21)00448-4

Declared interests

Prof Penny Ward: “I am semi-retired, but I am owner/Director of PWG Consulting (Biopharma) Ltd a consulting firm advising companies on drug and device development. Between December 2016 and July 2019 I served as Chief Medical Officer of Virion Biotherapeutics Ltd, a company developing antiviral treatments for respiratory viral diseases. Previous employee of Roche, makers of tocilizumab (anti IL6 antibody) and CMO of Novimmune, makers of empalumab (anti IFN gamma antibody).”