Oral Fluvoxamine With Inhaled Budesonide for Treatment of Early-Onset COVID-19

Reis et al., Annals of Internal Medicine, doi:10.7326/M22-3305, TOGETHER, NCT04727424 (history)

Reis et al., Oral Fluvoxamine With Inhaled Budesonide for Treatment of Early-Onset COVID-19, Annals of Internal Medicine, doi:10.7326/M22-3305, TOGETHER, NCT04727424

Apr 2023 Source PDF

Twitter
Facebook

All Studies Meta

Low-risk (1% hospitalization) outpatient RCT with 738 fluvoxamine + budesonide patients and 738 placebo patients, showing significantly lower hospitalization/ER visits with treatment.

Other arms of this trial show many critical issues [Reis], many of which may also apply to this arm.

1. Reis et al., New England Journal of Medicine, doi:10.1056/NEJMoa2115869 (results released 8/6/2021), Effect of Early Treatment with Ivermectin among Patients with Covid-19, https://www.nejm.org/doi/full/10.1056/NEJMoa2115869.

Important missing comments or errors? Let us know.

This study includes budesonide and fluvoxamine.

risk of death, 200.0% higher, RR 3.00, p = 1.00, treatment 1 of 738 (0.1%), control 0 of 738 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm).

risk of hospitalization, 12.5% lower, RR 0.88, p = 1.00, treatment 7 of 738 (0.9%), control 8 of 738 (1.1%), NNT 738.

hospitalization or ER >6hrs, 50.0% lower, RR 0.50, p = 0.04, treatment 13 of 738 (1.8%), control 27 of 738 (3.7%), NNT 53, adjusted per study, day 28, primary outcome.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Reis et al., 17 Apr 2023, Double Blind Randomized Controlled Trial, placebo-controlled, Brazil, peer-reviewed, 35 authors, study period 15 January, 2022 - 6 July, 2022, average treatment delay 3.0 days, this trial uses multiple treatments in the treatment arm (combined with budesonide) - results of individual treatments may vary, trial NCT04727424 (history) (TOGETHER).

All Studies Meta Analysis Submit Updates or Corrections

This Paper Fluvoxamine All

AI generated summary. Current AI models can provide useful summaries for non-experts, but may be inaccurate and have limited ability to analyze larger context such as the entire evidence base for fluvoxamine.

Oral Fluvoxamine With Inhaled Budesonide for Treatment of Early-Onset COVID-19 A Randomized Platform Trial

MD, PhD; Gilmar Reis, Eduardo Augusto, Moreira Santos, MD, PhD; Daniela Silva, Medeiros Carla, MD Silva, PhD Lehana Thabane, PhD Vitoria Helena, Souza Campos, ; Thiago, MD Santiago Ferreira, Castilho Vitor Quirino, Ana Santos, Ribeiro Maria, MD Ana Paula Nogueira, Guimaraes Figueiredo, MD Leonardo Almeida, Monteiro Cançado, MD Savassi, PhD Adhemar Dias, MD, PhD Figueiredo Neto, RN Carina Bitarães, RN Aline Cruz Milagres, MD ; Eduardo Diniz Callegari, Maria Izabel Campos Simplicio, Bscpharm ; Luciene, RN, MPH Barra Ribeiro, Rosemary Oliveira, PhD Ofir Harari, MSc Lindsay A Wilson, PhD, MPH Jamie I Forrest, MSc Hinda Ruton, PhD Sheila Sprague, MSc Paula Mckay, Christina M Guo, MD Gordon H Guyatt, PharmD Craig R Rayner, MD, MPH David R Boulware, MDCM, MPH Nicole Ezer, MD, MPH Todd C Lee, MD, MSc Emily Gibson Mcdonald, MBChB Mona Bafadhel, PhD Christopher Butler, MD Josue Rodrigues Silva, MD, MSc Mark Dybul, MD Edward J Mills

doi:10.7326/M22-3305

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.

Author contributions are available at Annals.org.

References

Bramante, Huling, Tignanelli, Randomized trial of metformin, ivermectin, and fluvoxamine for covid-19, N Engl J Med, doi:10.1056/NEJMoa2201662

Grambsch, Therneau, Proportional hazards tests and diagnostics based on weighted residuals, Biometrika, doi:10.1093/biomet/81.3.515

Guo, Harari, Chernecki, Fluvoxamine for the early treatment of COVID-19: A meta-analysis of randomized clinical trials, Am J Trop Med Hyg, doi:10.4269/ajtmh.21-1310

Lee, Vigod, Bortolussi-Courval, Fluvoxamine for outpatient management of COVID-19 to prevent hospitalization: A systematic review and meta-analysis, JAMA Netw Open, doi:10.1001/jamanetworkopen.2022.6269

Lenze, Mattar, Zorumski, Fluvoxamine vs placebo and clinical deterioration in outpatients with symptomatic COVID-19: A randomized clinical trial, JAMA, doi:10.1001/jama.2020.22760

Mills, Thorlund, Ioannidis, Calculating additive treatment effects from multiple randomized trials provides useful estimates of combination therapies, J Clin Epidemiol, doi:10.1016/j.jclinepi.2012.07.012

Omi, Tanimukai, Kanayama, Fluvoxamine alleviates ER stress via induction of Sigma-1 receptor, Cell Death Dis, doi:10.1038/cddis.2014.301

Park, Siden, Zoratti, Systematic review of basket trials, umbrella trials, and platform trials: a landscape analysis of ORIGINAL RESEARCH Oral Fluvoxamine With Inhaled Budesonide for Early-Onset COVID-19 master protocols, Trials, doi:10.1186/s13063-019-3664-1

Reis, Santos Moreira, Silva, Medeiros Silva, Thabane et al., Oral Fluvoxamine With Inhaled Budesonide for Early-Onset COVID-19 ORIGINAL RESEARCH Annals.org Author Contributions: Conception and design

Reis, Santos Moreira-Silva, Silva, 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, doi:10.1016/S2214-109X(21)00448-4

Reis, Santos, Silva, Silva, Effect of early treatment with metformin on risk of emergency care and hospitalization among patients with COVID-19: The TOGETHER randomized platform clinical trial, Lancet Reg Health Am, doi:10.1016/j.lana.2021.100142

Reis, Silva, Silva, A multi-center, adaptive, randomized, platform trial to evaluate the effect of repurposed medicines in outpatients with early coronavirus disease 2019 (COVID-19) and high-risk for complications: the TOGETHER master trial protocol, Gates Open Research

Reis, Silva, Silva, Early treatment with pegylated interferon lambda for covid-19, N Engl J Med, doi:10.1056/NEJMoa2209760

Reis, Silva, Silva, Effect of early treatment with hydroxychloroquine or lopinavir and ritonavir on risk of hospitalization among patients with COVID-19: the TOGETHER randomized clinical trial, JAMA Netw Open, doi:10.1001/jamanetworkopen.2021.6468

Reis, Silva, Silva, Effect of early treatment with ivermectin among patients with covid-19

Schandelmaier, Briel, Varadhan, Development of the Instrument to assess the Credibility of Effect Modification Analyses (ICEMAN) in randomized controlled trials and metaanalyses, CMAJ, doi:10.1503/cmaj.200077

Stanaland, Once-daily budesonide aqueous nasal spray for allergic rhinitis: a review, Clin Ther, doi:10.1016/s0149-2918(04)90050-1

Sukhatme, Reiersen, Vayttaden, Fluvoxamine: A review of its mechanism of action and its role in COVID-19, Front Pharmacol, doi:10.3389/fphar.2021.652688

Woodcock, Lavange, Master protocols to study multiple therapies, multiple diseases, or both, N Engl J Med, doi:10.1056/NEJMra1510062

Yu, Bafadhel, Dorward, Inhaled budesonide for COVID-19 in people at high risk of complications in the community in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial, Lancet, doi:10.1016/S0140-6736(21)01744-X

Download Image

Please send us corrections, updates, or comments. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.

Submit