Antiviral efficacy of fluoxetine in early symptomatic COVID-19: an open-label, randomised, controlled, adaptive platform trial (PLATCOV) DOI Creative Commons
Podjanee Jittamala, Simon Boyd, William HK Schilling

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 18, 2024

Abstract Background The selective serotonin reuptake inhibitors (SSRIs) fluoxetine and fluvoxamine were repurposed for the treatment of early COVID-19 based on their antiviral activity in vitro , observational clinical trial evidence suggesting they prevented progression to severe disease. However, these SSRIs have not been recommended guidelines vivo has characterised. Methods PLATCOV is an open-label, multicentre, phase 2, randomised, controlled, adaptive pharmacometric platform running Thailand, Brazil, Pakistan, Laos. We recruited low-risk adult outpatients aged 18-50 with symptomatic (symptoms <4 days). Patients assigned using block randomisation one eleven arms including oral (40mg/day 7 days), or no study drug. Uniform ratios applied across active groups while drug group comprised ≥20% patients at all times. primary endpoint was rate oropharyngeal viral clearance assessed a modified intention-to-treat population (>2 days follow-up). estimated under Bayesian hierarchical linear model fitted log10 densities standardised duplicate swab eluates taken daily over week (18 measurements per patient). This ongoing registered ClinicalTrials.gov ( NCT05041907 ). Findings Between 5 April 2022 8 May 2023 271 concurrently randomised either (n=120) (n=151). Fluoxetine well tolerated accelerated relative arm by 15% (95% credible interval (CrI): 2% 34%). In pooled meta-analysis unblinded substantially less than ritonavir-boosted nirmatrelvir-85% increase CrI: 61 112%); remdesivir 35% (14 59%), molnupiravir 37% 60%), casirivimab/imdevimab 29% (10 48%). Interpretation against SARS-CoV-2. Although level efficacy other currently available drugs, might still be useful prophylaxis where effect required. Funding Wellcome Trust Grant ref: 223195/Z/21/Z through Therapeutics Accelerator. Evidence before this proposed as therapeutics initially observational, evidence. reports suggested that taking had reduced probability developing dying. searched PubMed EMBASE studies English up until 30 th November search terms “fluoxetine”, “fluvoxamine” “COVID-19” restricted controlled trials (RCTs). Eight outpatient RCTs identified. There outpatients. A compatible moderate reduction hospitalisation death risk ratio 0.80 CI: 0.62,1.01). Added value showed illness SSRI weak . antivirals such nirmatrelvir molnupiravir. approach described here provides quantitative measure effects tractable sample sizes. Implications COVID-19. insufficient but, required prevent infection, could beneficial prophylaxis.

Language: Английский

Antiviral efficacy of fluoxetine in early symptomatic COVID-19: an open-label, randomised, controlled, adaptive platform trial (PLATCOV) DOI Creative Commons
Podjanee Jittamala, Simon Boyd, William HK Schilling

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 18, 2024

Abstract Background The selective serotonin reuptake inhibitors (SSRIs) fluoxetine and fluvoxamine were repurposed for the treatment of early COVID-19 based on their antiviral activity in vitro , observational clinical trial evidence suggesting they prevented progression to severe disease. However, these SSRIs have not been recommended guidelines vivo has characterised. Methods PLATCOV is an open-label, multicentre, phase 2, randomised, controlled, adaptive pharmacometric platform running Thailand, Brazil, Pakistan, Laos. We recruited low-risk adult outpatients aged 18-50 with symptomatic (symptoms <4 days). Patients assigned using block randomisation one eleven arms including oral (40mg/day 7 days), or no study drug. Uniform ratios applied across active groups while drug group comprised ≥20% patients at all times. primary endpoint was rate oropharyngeal viral clearance assessed a modified intention-to-treat population (>2 days follow-up). estimated under Bayesian hierarchical linear model fitted log10 densities standardised duplicate swab eluates taken daily over week (18 measurements per patient). This ongoing registered ClinicalTrials.gov ( NCT05041907 ). Findings Between 5 April 2022 8 May 2023 271 concurrently randomised either (n=120) (n=151). Fluoxetine well tolerated accelerated relative arm by 15% (95% credible interval (CrI): 2% 34%). In pooled meta-analysis unblinded substantially less than ritonavir-boosted nirmatrelvir-85% increase CrI: 61 112%); remdesivir 35% (14 59%), molnupiravir 37% 60%), casirivimab/imdevimab 29% (10 48%). Interpretation against SARS-CoV-2. Although level efficacy other currently available drugs, might still be useful prophylaxis where effect required. Funding Wellcome Trust Grant ref: 223195/Z/21/Z through Therapeutics Accelerator. Evidence before this proposed as therapeutics initially observational, evidence. reports suggested that taking had reduced probability developing dying. searched PubMed EMBASE studies English up until 30 th November search terms “fluoxetine”, “fluvoxamine” “COVID-19” restricted controlled trials (RCTs). Eight outpatient RCTs identified. There outpatients. A compatible moderate reduction hospitalisation death risk ratio 0.80 CI: 0.62,1.01). Added value showed illness SSRI weak . antivirals such nirmatrelvir molnupiravir. approach described here provides quantitative measure effects tractable sample sizes. Implications COVID-19. insufficient but, required prevent infection, could beneficial prophylaxis.

Language: Английский

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