Hospitalization Risk in High-Risk Patients With COVID-19 Treated With Fluvoxamine

Among patients with SARS-CoV-2 infection at increased risk for severe disease, treatment with fluvoxamine was found to decrease the risk for hospitalization, according to results of a study published in The Lancet Global Health.

As part of the ongoing TOGETHER trial, a placebo-controlled, randomized, adaptive platform trial was conducted in Brazil among high-risk symptomatic adults with a confirmed diagnosis of SARS-CoV-2 infection (ClinicalTrials.gov, NCT04727424). Eligible patients were recruited from 11 clinical sites and had a known risk factor for progression to severe disease. Patients were randomly assigned in a 1:1 fashion to receive either fluvoxamine 100 mg or placebo twice daily; all researchers and study patients were blinded to the treatment allocation. The primary outcome was hospitalization, defined as either retention in a COVID-19 emergency setting or transfer to a tertiary hospital due to COVID-19 up to day 28 following randomization.

Among patients included in the final analysis, 741 received fluvoxamine and 756 received placebo. Hospitalization or transfer to a tertiary hospital occurred among 79 (11%) patients in the fluvoxamine group compared with 119 (16%) in the placebo group, the majority of which were hospitalizations (87%). Fluvoxamine treatment was found to decrease the risk for hospitalization (relative risk [RR], 0.68; 95% Bayesian credible interval [BCI], 0.52-0.88) with a probability of superiority of 99.8%, which surpassed the prespecified superiority threshold of 97.6% (risk difference, 5.0%). Of note, the risk for hospitalization following fluvoxamine treatment was similar in a modified intention-to-treat analysis (RR, 0.69; 95% BCI, 0.53-0.90) and increased  in the per-protocol analysis (RR, 0.34; 95% BCI, 0.21-0.54).

In the primary intention-to-treat analysis, there were 17 and 25 deaths among patients in the fluvoxamine and placebo groups, respectively (odds ratio [OR], 0.68; 95% CI, 0.36-1.27). In the per-protocol population, there were 1 and 12 deaths among patients in the fluvoxamine and placebo groups, respectively (OR, 0.09; 95% CI, 0.01-0.47). Of note, there were no significant differences in the number of treatment emergent adverse events that occurred between the groups.

Limitations of this study were largely related to challenges of conducting a study on a disease that is not well characterized. In addition, as the study progressed, COVID-19 vaccines became widely available in Brazil and the study’s inclusion criteria were modified to permit vaccinated patients.

According to the researchers, “Use of interventions, including fluvoxamine, to prevent progression of illness and hospitalization is critically dependent on identifying [patients at increased risk for severe disease].” In addition, “these considerations raise the importance of the development of a validated prediction rule for deterioration in patients in the early stages of COVID-19 infection,” the researchers concluded.

Disclosure: Some author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Reis G, Dos Santos Moreira-Silva EA, Medeiros Silva DC, et al. Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial. Lancet Glob Health. Published online October 27, 2021. doi: 10.1016/S2214-109X(21)00448-4