Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19
MD Eric J Lenze, MD Caline Mattar, MD Charles F Zorumski, BA Angela Stevens, Julie Schweiger, MD Ginger E Nicol, J Philip Miller, MPH Lei Yang, MSIS Michael Yingling, MS Michael S Avidan, MBBCh Angela M Reiersen
IMPORTANCE Coronavirus disease 2019 (COVID-19) may lead to serious illness as a result of an excessive immune response. Fluvoxamine may prevent clinical deterioration by stimulating the σ-1 receptor, which regulates cytokine production. OBJECTIVE To determine whether fluvoxamine, given during mild COVID-19 illness, prevents clinical deterioration and decreases the severity of disease. DESIGN, SETTING, AND PARTICIPANTS Double-blind, randomized, fully remote (contactless) clinical trial of fluvoxamine vs placebo. Participants were community-living, nonhospitalized adults with confirmed severe acute respiratory syndrome coronavirus 2 infection, with COVID-19 symptom onset within 7 days and oxygen saturation of 92% or greater. One hundred fifty-two participants were enrolled from the St Louis metropolitan area (Missouri and Illinois) from April 10, 2020, to August 5, 2020. The final date of follow-up was September 19, 2020. INTERVENTIONS Participants were randomly assigned to receive 100 mg of fluvoxamine (n = 80) or placebo (n = 72) 3 times daily for 15 days.
MAIN OUTCOMES AND MEASURES The primary outcome was clinical deterioration within 15 days of randomization defined by meeting both criteria of (1) shortness of breath or hospitalization for shortness of breath or pneumonia and (2) oxygen saturation less than 92% on room air or need for supplemental oxygen to achieve oxygen saturation of 92% or greater.
RESULTS Of 152 patients who were randomized (mean [SD] age, 46  years; 109 [72%] women), 115 (76%) completed the trial. Clinical deterioration occurred in 0 of 80 patients in the fluvoxamine group and in 6 of 72 patients in the placebo group (absolute difference, 8.7% [95% CI, 1.8%-16.4%] from survival analysis; log-rank P = .009). The fluvoxamine group had 1 serious adverse event and 11 other adverse events, whereas the placebo group had 6 serious adverse events and 12 other adverse events.
CONCLUSIONS AND RELEVANCE In this preliminary study of adult outpatients with symptomatic COVID-19, patients treated with fluvoxamine, compared with placebo, had a lower likelihood of clinical deterioration over 15 days. However, the study is limited by a small sample size and short follow-up duration, and determination of clinical efficacy would require larger randomized trials with more definitive outcome measures.
Adverse Events The fluvoxamine group had 1 serious adverse event and 11 other adverse events, whereas the placebo group had 6 serious adverse events and 12 other adverse events (Table 3 and eResults 1 in Supplement 2). Pneumonia and gastrointestinal symptoms (such as nausea and vomiting) occurred more often in the placebo group compared with those who received fluvoxamine.
Missing Data In terms of missing data, 517 of 3943 follow-up surveys (13%) were not filled out by participants. The mean score for those Body mass index category, No. (%) c Underweight (<18.5) 1 Normal (18.5-24.9) 14 (18) 7 (10) Overweight (25-29. ). For primary prevention, traditional public health approaches include wearing masks, physical distancing, contact tracing, and quarantine. These steps are the current standard of care as the world awaits the results of randomized trials of vaccines and monoclonal antibodies. For the treatment of patients with serious illness in the hospital, corticosteroids have emerged as the standard of care. 1, 2 But what about treatments for patients with COVID-19 who are neither hospitalized nor severely ill? The pilot study by Lenze and colleagues 3 addresses a critically important question during the pandemic of how to prevent individuals who acquire COVID-19 from deteriorating to serious illness. 4 If an effective treatment is found for this key gap in treatment, it will affect the health of millions of people worldwide. This study has important..
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