학술논문
Oral Fluvoxamine With Inhaled Budesonide for Treatment of Early-Onset COVID-19 : A Randomized Platform Trial.
Document Type
Academic Journal
Author
Reis G; ViRx@Stanford, Stanford Biosecurity and Pandemic Preparedness Initiative, Stanford, California; Research Division, Cardresearch - Cardiologia Assistencial e de Pesquisa, Belo Horizonte, Brazil; Department of Medicine, Pontifícia Universidade Católica de Minas Gerais, Minas Gerais, Brazil; and Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada (G.R.).; Dos Santos Moreira Silva EA; Research Division, Cardresearch - Cardiologia Assistencial e de Pesquisa, Belo Horizonte, Brazil, and Department of Medicine, Pontifícia Universidade Católica de Minas Gerais, Minas Gerais, Brazil (E.A.d.S.M.S., D.C.M.S., V.H.d.S.C., C.V.Q.d.S.).; Medeiros Silva DC; Research Division, Cardresearch - Cardiologia Assistencial e de Pesquisa, Belo Horizonte, Brazil, and Department of Medicine, Pontifícia Universidade Católica de Minas Gerais, Minas Gerais, Brazil (E.A.d.S.M.S., D.C.M.S., V.H.d.S.C., C.V.Q.d.S.).; Thabane L; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada (L.T., S.S., P.M., G.H.G.).; de Souza Campos VH; Research Division, Cardresearch - Cardiologia Assistencial e de Pesquisa, Belo Horizonte, Brazil, and Department of Medicine, Pontifícia Universidade Católica de Minas Gerais, Minas Gerais, Brazil (E.A.d.S.M.S., D.C.M.S., V.H.d.S.C., C.V.Q.d.S.).; Ferreira TS; Research Division, Cardresearch - Cardiologia Assistencial e de Pesquisa, Belo Horizonte, Brazil (T.S.F., M.I.C.S., L.B.R., R.O.).; Quirino Dos Santos CV; Research Division, Cardresearch - Cardiologia Assistencial e de Pesquisa, Belo Horizonte, Brazil, and Department of Medicine, Pontifícia Universidade Católica de Minas Gerais, Minas Gerais, Brazil (E.A.d.S.M.S., D.C.M.S., V.H.d.S.C., C.V.Q.d.S.).; Ribeiro Nogueira AM; Public Health Care Division, City of Ibirité, Brazil (A.M.R.N.).; Figueiredo Guimaraes Almeida AP; Department of Public Health at UNIFIPMoc and Family Medicine Fellowship Program, City of Montes Claros, Brazil (A.P.F.G.A.).; Cançado Monteiro Savassi L; Public Health, Mental and Family Medicine Department, Ouro Preto Federal University, Minas Gerais, Brazil (L.C.M.S.).; de Figueiredo Neto AD; Public Health Fellowship Program, Governador Valadares Public Health Authority, Minas Gerais, Brazil (A.D.d.F.N.).; Bitarães C; Public Health, Mental and Family Medicine Department, Ouro Preto Federal University, Minas Gerais, Brazil, and Public Health Care Division, City of Ibirité, Brazil (C.B., A.C.M.).; Cruz Milagres A; Public Health, Mental and Family Medicine Department, Ouro Preto Federal University, Minas Gerais, Brazil, and Public Health Care Division, City of Ibirité, Brazil (C.B., A.C.M.).; Diniz Callegari E; Department of Public Health at UNIFIPMoc and Family Medicine Fellowship Program, City of Montes Claros, Brazil, and Public Health Care Division, City of Brumadinho, Brazil (E.D.C.).; Campos Simplicio MI; Research Division, Cardresearch - Cardiologia Assistencial e de Pesquisa, Belo Horizonte, Brazil (T.S.F., M.I.C.S., L.B.R., R.O.).; Barra Ribeiro L; Research Division, Cardresearch - Cardiologia Assistencial e de Pesquisa, Belo Horizonte, Brazil (T.S.F., M.I.C.S., L.B.R., R.O.).; Oliveira R; Research Division, Cardresearch - Cardiologia Assistencial e de Pesquisa, Belo Horizonte, Brazil (T.S.F., M.I.C.S., L.B.R., R.O.).; Harari O; Cytel, Vancouver, British Columbia, Canada (O.H., H.R.).; Wilson LA; Platform Life Sciences, Vancouver, British Columbia, Canada (L.A.W., J.I.F., C.M.G., J.R.S.).; Forrest JI; Platform Life Sciences, Vancouver, British Columbia, Canada (L.A.W., J.I.F., C.M.G., J.R.S.).; Ruton H; Cytel, Vancouver, British Columbia, Canada (O.H., H.R.).; Sprague S; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada (L.T., S.S., P.M., G.H.G.).; McKay P; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada (L.T., S.S., P.M., G.H.G.).; Guo CM; Platform Life Sciences, Vancouver, British Columbia, Canada (L.A.W., J.I.F., C.M.G., J.R.S.).; Guyatt GH; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada (L.T., S.S., P.M., G.H.G.).; Rayner CR; Certara, Princeton, New Jersey, and Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Victoria, Australia (C.R.R.).; Boulware DR; Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota (D.R.B.).; Ezer N; Department of Medicine, Division of Respiratory Medicine, McGill University Health Centre, Montréal, Québec, Canada (N.E.).; Lee TC; Division of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montréal, Québec, Canada (T.C.L.).; McDonald EG; Division of General Internal Medicine, Department of Medicine, McGill University Health Centre, Montréal, Québec, Canada (E.G.M.).; Bafadhel M; School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom (M.B.).; Butler C; Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom (C.B.).; Rodrigues Silva J; Platform Life Sciences, Vancouver, British Columbia, Canada (L.A.W., J.I.F., C.M.G., J.R.S.).; Dybul M; Global Health Institute, Georgetown University, Washington, DC (M.D.).; Mills EJ; ViRx@Stanford, Stanford Biosecurity and Pandemic Preparedness Initiative, Stanford, California; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada; Cytel, Vancouver, British Columbia, Canada; and Platform Life Sciences, Vancouver, British Columbia, Canada (E.J.M.).
Source
Publisher: American College of Physicians--American Society of Internal Medicine Country of Publication: United States NLM ID: 0372351 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1539-3704 (Electronic) Linking ISSN: 00034819 NLM ISO Abbreviation: Ann Intern Med Subsets: MEDLINE
Subject
Language
English
Abstract
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.
Primary Funding Source: Latona Foundation, FastGrants, and Rainwater Charitable Foundation.
Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M22-3305.
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.
Primary Funding Source: Latona Foundation, FastGrants, and Rainwater Charitable Foundation.
Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M22-3305.