Fluvoxamine Treatment of Patients with Symptomatic COVID-19 in a Community Treatment Center: A Preliminary Result of Randomized Controlled Trial

Abstract

Background This study aimed to evaluate whether fluvoxamine reduces clinical deterioration in adult patients with mild to moderate coronavirus disease 2019 (COVID-19), and to identify risk factors for clinical deterioration in patients admitted to a community treatment center (CTC). Materials and Methods A randomized, placebo-controlled trial was conducted in a CTC, in Seoul, Korea from January 15, 2021, to February 19, 2021. Symptomatic adult patients with positive results of severe acute respiratory syndrome coronavirus 2 real time-polymerase chain reaction within 3 days of randomization were assigned at random to receive 100 mg of fluvoxamine or placebo twice daily for 10 days. The primary outcome was clinical deterioration defined by any of the following criteria: oxygen requirement to keep oxygen saturation over 94.0%, aggravation of pneumonia with dyspnea, or World Health Organization clinical progression scale 4 or greater. Results Of 52 randomized participants [median (interquartile range) age, 53.5 (43.3 - 60.0) years; 31 (60.0%) men], 44 (85.0%) completed the trial. Clinical deterioration occurred in 2 of 26 patients in each group ( P >0.99). There were no serious adverse events in either group. Clinical deterioration occurred in 15 (6.0%) of 271 patients admitted to the CTC, and all of them were transferred to a hospital. In multivariate analysis, age between 55 and 64, fever and pneumonia at admission were independent risk factors for clinical deterioration. Conclusion In this study of adult patients with symptomatic COVID-19 who were admitted to the CTC, there was no significant differences in clinical deterioration between patients treated with fluvoxamine and placebo (ClinicalTrials.gov Identifier: NCT04711863 ).

Fluvoxamine for COVID‐19 outpatients: For the time being, we might prefer to curb our optimism

“… 8 It was stopped early for operational reasons, 8 and the primary outcome (defined as in the Stop COVID trials) was observed in 2/26 treated and 2/26 placebo patients. 8 Figure 1 depicts meta‐analysis of study‐defined primary outcomes and of hospitalizations that uses the same frequentist and Bayesian methodology as used by Lee et al . 3 except that it includes the Korean data 8 and employs Hartung–Knapp–Sidik–Jonkman correction shown to improve confidence interval coverage with small number of trials differing in size 9 : (i) for both outcomes, frequentist point‐estimates are closely similar to those published, 3 , 4 but indicators of uncertainty are more obvious—CIs are wider (and embrace unity; imprecision), and prediction intervals are wide (heterogeneity; Figure 1 ); (ii) Bayes point‐estimate for hospitalizations (Figure 1B ) indicates somewhat less risk reduction (RR = 0.819) than published 3 (RR = 0.78) and CIs and (wide) prediction intervals are shifted to the right (imprecision, heterogeneity).…”

“…Two further points additionally illustrate current uncertainty about the effect of fluvoxamine. First, the proportions reported in the 2 smaller trials (Stop COVID 1, 5 signalling a potentially large benefit and the Korean trial 8 signalling no potential benefit) are fragile (numerically unstable): it can be shown that even under the assumption of a marked fluvoxamine effect 1 or 2 events more in the fluvoxamine arms and 1 or 2 fewer in the placebo arms would be equally as probable as the observed numbers of events. Next, estimates of heterogeneity across trials that substantially differ in size are problematic.…”

“…the published meta‐analyses 3 , 4 are in that: (i) it includes data from the Korean trial (Seo et al . 8 ) and (ii) uses Hartung–Knapp–Sidik–Jonkman correction to calculate frequentist confidence intervals, as recommended. 9 (A) Meta‐analysis of study‐defined primary outcomes (explained in the text).…”

Correspondence on Fluvoxamine Treatment of Patients with Symptomatic COVID-19

“…We would like to correspond and share ideas on the publication “Fluvoxamine treatment of patients with symptomatic COVID-19 in a community treatment center: a preliminary result of randomized controlled trial” [ 1 ]. According to Seo et al, there were no significant differences in clinical worsening between patients treated with fluvoxamine and those treated with a placebo in this research of adult patients with symptomatic coronavirus disease 2019 (COVID-19) who were admitted to the community treatment center [ 1 ]. There are several new proposed alternative treatments against COVID-19, including fluvoxamine.…”

Reply: Correspondence on Fluvoxamine Treatment of Patients with Symptomatic COVID-19

“…In the TOGETHER trial, enrolled patients had at least one criterion for high risk; diabetes, systemic arterial hypertension requiring at least one medication, known cardiovascular diseases, symptomatic lung diseases, smoking, obesity, having had a transplant, chronic kidney disease, immunosuppressive therapy, history of cancer or aged 50 years or older. However, we enrolled adult patients admitted to a community treatment center, who usually had no or minimum comorbidities [ 5 ]. We excluded patients with severe underlying lung diseases, chronic liver diseases, congestive heart failure, chronic kidney disease, or those who were immunocompromised.…”