The STOP COVID 2 study: Fluvoxamine vs placebo for outpatients with symptomatic COVID-19, a fully-remote randomized controlled trial
MD, MPE Angela M Reiersen, MD Caline Mattar, Rachel A Bender Ignacio, MD, MPH David R Boulware, MD, MPH Todd C Lee, MD Rachel Hess, Alexander J Lankowski, MDCM, MSc, FRCPC Emily G Mcdonald, J Philip Miller, MD William G Powderly, MD Matthew F Pullen, MD, MPH Jeffrey T Rado, MD Michael W Rich, MD, MSc Joshua T Schiffer, Julie Schweiger, MD Adam M Spivak, BS Angela Stevens, MD, MSc, FRCPC Simone N Vigod, MD Payal Agarwal, MPH, MSIS Lei Yang, MS Michael Yingling, PhD Torie R Gettinger, MD Charles F Zorumski, MD Eric J Lenze
Open Forum Infectious Diseases, doi:10.1093/ofid/ofad419
Background: Prior randomized clinical trials have reported benefit of fluvoxamine >200mg/day vs placebo for patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Methods: This randomized, double-blind, placebo-controlled, fully-remote multi-site clinical trial evaluated whether fluvoxamine prevents clinical deterioration in higher-risk outpatients with acute COVID-19. Between December 2020 and May 2021, non-hospitalized US and Canadian participants with confirmed symptomatic infection received fluvoxamine (50mg on Day 1, 100mg twice daily thereafter) or placebo for 15 days. The primary modified intent -to-treat (mITT) population included participants who started the intervention within 7 days of symptom onset with a baseline oxygen saturation ≥ 92%. The primary outcome was clinical deterioration within 15 days of randomization defined as having both (1) shortness of breath (severity ≥ 4 on 0-10 scale or requiring hospitalization), and (2) oxygen saturation <92% on room air or need for supplemental oxygen. Results: A total of 547 participants were randomized and met mITT criteria (n=272 fluvoxamine, n=275 placebo). The Data Safety Monitoring Board recommended stopping early for futility related to lower than predicted event rate and declining accrual concurrent with vaccine availability in the U.S. and Canada. Clinical deterioration occurred in 13 (4.8%) participants in the fluvoxamine group and 15 (5.5%) participants in the placebo group (absolute difference at day 15, 0.68% [95% CI, -3.0 % to 4.4 %]; log rank P=0.91). Conclusions: This trial did not find fluvoxamine efficacious in preventing clinical deterioration in unvaccinated outpatients with symptomatic COVID-19. It was stopped early and underpowered due to low primary outcome rates.
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'reference-count': 14,
'publisher': 'Oxford University Press (OUP)',
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'timestamp': 1691366400000},
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'abstract': '<jats:title>Abstract</jats:title>\n'
' <jats:sec>\n'
' <jats:title>Background</jats:title>\n'
' <jats:p>Prior randomized clinical trials have reported benefit of '
'fluvoxamine ≥200\u2005mg/d vs placebo for patients infected with severe acute respiratory '
'syndrome coronavirus 2 (SARS-CoV-2).</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Methods</jats:title>\n'
' <jats:p>This randomized, double-blind, placebo-controlled, fully remote '
'multisite clinical trial evaluated whether fluvoxamine prevents clinical deterioration in '
'higher-risk outpatients with acute coronavirus disease 2019 (COVID-19). Between December 2020 '
'and May 2021, nonhospitalized US and Canadian participants with confirmed symptomatic '
'infection received fluvoxamine (50\u2005mg on day 1, 100\u2005mg twice daily thereafter) or '
'placebo for 15 days. The primary modified intent-to-treat (mITT) population included '
'participants who started the intervention within 7 days of symptom onset with a baseline '
'oxygen saturation ≥92%. The primary outcome was clinical deterioration within 15 days of '
'randomization, defined as having both (1) shortness of breath (severity ≥4 on a 0–10 scale or '
'requiring hospitalization) and (2) oxygen saturation &lt;92% on room air or need for '
'supplemental oxygen.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Results</jats:title>\n'
' <jats:p>A total of 547 participants were randomized and met mITT criteria '
'(n = 272 fluvoxamine, n = 275 placebo). The Data Safety Monitoring Board recommended stopping '
'early for futility related to lower-than-predicted event rates and declining accrual '
'concurrent with vaccine availability in the United States and Canada. Clinical deterioration '
'occurred in 13 (4.8%) participants in the fluvoxamine group and 15 (5.5%) participants in the '
'placebo group (absolute difference at day 15, 0.68%; 95% CI, −3.0% to 4.4%; log-rank P = '
'.91).</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Conclusions</jats:title>\n'
' <jats:p>This trial did not find fluvoxamine efficacious in preventing '
'clinical deterioration in unvaccinated outpatients with symptomatic COVID-19. It was stopped '
'early and underpowered due to low primary outcome rates.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Clinical Trials Registration</jats:title>\n'
' <jats:p>ClinicalTrials.gov Identifier: NCT04668950.</jats:p>\n'
' </jats:sec>',
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