TY - JOUR
T1 - Oral Fluvoxamine With Inhaled Budesonide for Treatment of Early-Onset COVID-19 A Randomized Platform Trial
AU - the TOGETHER Investigators
AU - Reis, Gilmar
AU - Augusto dos Santos Moreira Silva, Eduardo
AU - Silva, Daniela Carla Medeiros
AU - Thabane, Lehana
AU - Helena de Souza Campos, Vitoria
AU - Ferreira, Thiago Santiago
AU - Quirino dos Santos, Castilho Vitor
AU - Nogueira, Ana Maria Ribeiro
AU - Guimaraes Almeida, Ana Paula Figueiredo
AU - Savassi, Leonardo Cançado Monteiro
AU - Dias de Figueiredo Neto, Adhemar
AU - Bitarães, Carina
AU - Milagres, Aline Cruz
AU - Callegari, Eduardo Diniz
AU - Simplicio, Maria Izabel Campos
AU - Ribeiro, Luciene Barra
AU - Oliveira, Rosemary
AU - Harari, Ofir
AU - Wilson, Lindsay A.
AU - Forrest, Jamie I.
AU - Ruton, Hinda
AU - Sprague, Sheila
AU - McKay, Paula
AU - Guo, Christina M.
AU - Guyatt, Gordon H.
AU - Rayner, Craig R.
AU - Boulware, David R.
AU - Ezer, Nicole
AU - Lee, Todd C.
AU - McDonald, Emily Gibson
AU - Bafadhel, Mona
AU - Butler, Christopher
AU - Silva, Josue Rodrigues
AU - Dybul, Mark
AU - Mills, Edward J.
N1 - Publisher Copyright:
© 2023 American College of Physicians.
PY - 2023/5/1
Y1 - 2023/5/1
N2 - Background: Previous trials have demonstrated the effects of fluvoxamine alone and inhaled budesonide alone for prevention of disease progression among outpatients with COVID-19. Objective: To determine whether the combination of fluvoxamine and inhaled budesonide would increase treatment effects in a highly vaccinated population. Design: Randomized, placebo-controlled, adaptive platform trial. (ClinicalTrials.gov: NCT04727424) Setting: 12 clinical sites in Brazil. Participants: Symptomatic adults with confirmed SARS-CoV-2 infection and a known risk factor for progression to severe disease. Intervention: Patients were randomly assigned to either fluvoxamine (100 mg twice daily for 10 days) plus inhaled budesonide (800 mcg twice daily for 10 days) or matching placebos. Measurements: The primary outcome was a composite of emergency setting retention for COVID-19 for more than 6 hours, hospitalization, and/or suspected complications due to clinical progression of COVID-19 within 28 days of randomization. Secondary outcomes included health care attendance (defined as hospitalization for any cause or emergency department visit lasting >6 hours), time to hospitalization, mortality, patient-reported outcomes, and adverse drug reactions. Results: Randomization occurred from 15 January to 6 July 2022. A total of 738 participants were allocated to oral fluvoxamine plus inhaled budesonide, and 738 received placebo. The proportion of patients observed in an emergency setting for COVID-19 for more than 6 hours or hospitalized due to COVID-19 was lower in the treatment group than the placebo group (1.8% [95% credible interval {CrI}, 1.1% to 3.0%] vs. 3.7% [95% CrI, 2.5% to 5.3%]; relative risk, 0.50 [95% CrI, 0.25 to 0.92]), with a probability of superiority of 98.7%. No relative effects were found between groups for any of the secondary outcomes. More adverse events occurred in the intervention group than the placebo group, but no important differences between the groups were detected. Limitation: Low event rate overall, consistent with contemporary trials in vaccinated populations. Conclusion: Treatment with oral fluvoxamine plus inhaled budesonide among high-risk outpatients with early COVID-19 reduced the incidence of severe disease requiring advanced care.
AB - Background: Previous trials have demonstrated the effects of fluvoxamine alone and inhaled budesonide alone for prevention of disease progression among outpatients with COVID-19. Objective: To determine whether the combination of fluvoxamine and inhaled budesonide would increase treatment effects in a highly vaccinated population. Design: Randomized, placebo-controlled, adaptive platform trial. (ClinicalTrials.gov: NCT04727424) Setting: 12 clinical sites in Brazil. Participants: Symptomatic adults with confirmed SARS-CoV-2 infection and a known risk factor for progression to severe disease. Intervention: Patients were randomly assigned to either fluvoxamine (100 mg twice daily for 10 days) plus inhaled budesonide (800 mcg twice daily for 10 days) or matching placebos. Measurements: The primary outcome was a composite of emergency setting retention for COVID-19 for more than 6 hours, hospitalization, and/or suspected complications due to clinical progression of COVID-19 within 28 days of randomization. Secondary outcomes included health care attendance (defined as hospitalization for any cause or emergency department visit lasting >6 hours), time to hospitalization, mortality, patient-reported outcomes, and adverse drug reactions. Results: Randomization occurred from 15 January to 6 July 2022. A total of 738 participants were allocated to oral fluvoxamine plus inhaled budesonide, and 738 received placebo. The proportion of patients observed in an emergency setting for COVID-19 for more than 6 hours or hospitalized due to COVID-19 was lower in the treatment group than the placebo group (1.8% [95% credible interval {CrI}, 1.1% to 3.0%] vs. 3.7% [95% CrI, 2.5% to 5.3%]; relative risk, 0.50 [95% CrI, 0.25 to 0.92]), with a probability of superiority of 98.7%. No relative effects were found between groups for any of the secondary outcomes. More adverse events occurred in the intervention group than the placebo group, but no important differences between the groups were detected. Limitation: Low event rate overall, consistent with contemporary trials in vaccinated populations. Conclusion: Treatment with oral fluvoxamine plus inhaled budesonide among high-risk outpatients with early COVID-19 reduced the incidence of severe disease requiring advanced care.
UR - http://www.scopus.com/inward/record.url?scp=85159734722&partnerID=8YFLogxK
U2 - 10.7326/M22-3305
DO - 10.7326/M22-3305
M3 - Article
C2 - 37068273
AN - SCOPUS:85159734722
SN - 0003-4819
VL - 176
SP - 667
EP - 675
JO - Annals of internal medicine
JF - Annals of internal medicine
IS - 5
ER -
