Fluvoxamine for symptomatic outpatients with COVID-19.
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ABSTRACT:
SUBMITTER: Wu PE
PROVIDER: S-EPMC8863199 | biostudies-literature | 2022 Feb
REPOSITORIES: biostudies-literature
Publications
Fluvoxamine for symptomatic outpatients with COVID-19.
Wu Peter E PE Austin Emily E Leong Derek D
CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 20220119 7
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Project description:ImportanceCoronavirus disease 2019 (COVID-19) may lead to serious illness as a result of an excessive immune response. Fluvoxamine may prevent clinical deterioration by stimulating the σ-1 receptor, which regulates cytokine production.ObjectiveTo determine whether fluvoxamine, given during mild COVID-19 illness, prevents clinical deterioration and decreases the severity of disease.Design, setting, and participantsDouble-blind, randomized, fully remote (contactless) clinical trial of fluvoxamine vs placebo. Participants were community-living, nonhospitalized adults with confirmed severe acute respiratory syndrome coronavirus 2 infection, with COVID-19 symptom onset within 7 days and oxygen saturation of 92% or greater. One hundred fifty-two participants were enrolled from the St Louis metropolitan area (Missouri and Illinois) from April 10, 2020, to August 5, 2020. The final date of follow-up was September 19, 2020.InterventionsParticipants were randomly assigned to receive 100 mg of fluvoxamine (n = 80) or placebo (n = 72) 3 times daily for 15 days.Main outcomes and measuresThe primary outcome was clinical deterioration within 15 days of randomization defined by meeting both criteria of (1) shortness of breath or hospitalization for shortness of breath or pneumonia and (2) oxygen saturation less than 92% on room air or need for supplemental oxygen to achieve oxygen saturation of 92% or greater.ResultsOf 152 patients who were randomized (mean [SD] age, 46 [13] years; 109 [72%] women), 115 (76%) completed the trial. Clinical deterioration occurred in 0 of 80 patients in the fluvoxamine group and in 6 of 72 patients in the placebo group (absolute difference, 8.7% [95% CI, 1.8%-16.4%] from survival analysis; log-rank P = .009). The fluvoxamine group had 1 serious adverse event and 11 other adverse events, whereas the placebo group had 6 serious adverse events and 12 other adverse events.Conclusions and relevanceIn this preliminary study of adult outpatients with symptomatic COVID-19, patients treated with fluvoxamine, compared with placebo, had a lower likelihood of clinical deterioration over 15 days. However, the study is limited by a small sample size and short follow-up duration, and determination of clinical efficacy would require larger randomized trials with more definitive outcome measures.Trial registrationClinicalTrials.gov Identifier: NCT04342663.
| S-EPMC7662481 | biostudies-literature
Project description:BackgroundPrior randomized clinical trials have reported benefit of fluvoxamine ≥200 mg/d vs placebo for patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).MethodsThis 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 mg on day 1, 100 mg 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 <92% on room air or need for supplemental oxygen.ResultsA 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).ConclusionsThis 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.Clinical trials registrationClinicalTrials.gov Identifier: NCT04668950.
| S-EPMC10445518 | biostudies-literature
Project description: Not available
| S-EPMC9473347 | biostudies-literature
Project description: Not available
| S-EPMC8846600 | biostudies-literature
Project description: Not available
| S-EPMC8846616 | biostudies-literature
Project description: Not available
| S-EPMC8846601 | biostudies-literature
Project description: Not available
| S-EPMC8926898 | biostudies-literature
Project description:ObjectivesThere is little in-depth qualitative evidence of how symptoms manifest themselves in outpatients with COVID-19 and how these in turn impact outpatients' daily lives. The objective of the study was therefore to explore the experience of outpatients with COVID-19 qualitatively, concerning the symptomatic experience and its subsequent impact on daily life.SettingQualitative research study comprising virtual in-depth, open-ended interviews with outpatients and clinicians.ParticipantsThirty US adult patients with COVID-19 were interviewed within 21 days of diagnosis. Patients were 60% female and 87% white, who had to self-report one of the following: fever, cough, shortness of breath/difficulty breathing, change/loss of taste/smell, vomiting/diarrhoea or body/muscle aches. Five independent clinicians were also interviewed about their experience treating outpatients.Primary and secondary outcome measuresTranscripts were analysed thematically to organise symptoms and impacts of daily life into higher-order overarching categories, and subsequently propose a conceptual model. The adequacy of the sample size was assessed by conceptual saturation analysis.ResultsPatient-reported concepts were organised into six symptom themes (upper respiratory, lower respiratory, systemic, gastrointestinal, smell and taste, and other) and seven impact themes (activities of daily living, broad daily activities, leisure/social activities, and physical, emotional, professional and quarantine-specific impacts). Symptom type, severity, duration and time of onset varied by patient. Clinicians endorsed all patient-reported symptoms.ConclusionsThe manifestation of symptoms in outpatients is heterogeneous and affects all aspects of daily life. Outpatients offered new detailed insights into their symptomatic experiences, including heterogeneous experiences of smell and taste, and the impacts that symptoms had on their daily lives. Findings of this research may be used to supplement existing knowledge of the outpatient experience of mild-to-moderate COVID-19, to further inform treatment guidelines and to provide an evidence base for evaluating potential treatment benefits.
| S-EPMC9062460 | biostudies-literature
Project description:Objective This double-blind RCT investigated raising serum 25-hydroxyvitamin D (25D) with extended-release calcifediol (ERC) on time to symptom resolution in mild to moderate COVID-19. Research Methods & Procedures COVID-19 outpatients received oral ERC (300 mcg on Days 1-3 and 60 mcg on Days 4-27) or placebo (NCT04551911). Symptoms were self-reported daily. Primary endpoints were raising 25D to ≥50 ng/mL and decreasing resolution time for five aggregated symptoms (three respiratory). Results 171 subjects were randomized, 160 treated and 134 (65 ERC, 69 placebo) retained. Average age was 43 (range: 18-71), 59% female, mean baseline 25D was 37±1 (SE) ng/mL. In the full analysis set (FAS), 81% of ERC subjects achieved 25D levels of ≥50 ng/mL versus 15% with placebo (p<0.0001). In the per-protocol (PP) population, mean 25D increased with ERC to 82±4 (SE) ng/mL (p<0.0001) by Day 7; placebo trended lower. Symptom resolution time was unchanged in the FAS by ERC (hazard ratio of 0.983; 95% CI 0.695, 1.390; p=0.922). In the PP population, respiratory symptoms resolved 4.0 days faster when 25D was elevated above baseline level at both Days 7 and 14 (median of 6.5 versus 10.5 days; hazard ratio 1.372; 95% CI 0.945, 1.991; p=0.0962; Wilcoxon p=0.0386). Symptoms resolved in both treatment groups to a similar extent by study end. Safety concerns including hypercalcemia were absent with ERC treatment. Conclusion ERC safely raised serum 25D to at least 50 ng/mL in COVID-19 outpatients, possibly accelerating resolution of respiratory symptoms and mitigating pneumonia risk. These findings warrant further study.
| S-EPMC9639413 | biostudies-literature
Project description:BackgroundWhile SARS-CoV-2 infectious virus isolation in outpatients with COVID-19 has been associated with viral RNA levels and symptom duration, little is known about the host, disease and viral determinants of infectious virus detection.MethodsCOVID-19 adult outpatients were enrolled within 7 days of symptom onset. Clinical symptoms were recorded via patient diary. Nasopharyngeal swabs were collected to quantitate SARS-CoV-2 RNA by reverse transcriptase polymerase chain reaction and for infectious virus isolation in Vero E6-cells. SARS-CoV-2 antibodies were measured in serum using a validated ELISA assay.ResultsAmong 204 participants with mild-to-moderate symptomatic COVID19, the median nasopharyngeal viral RNA was 6.5 (IQR 4.7-7.6 log10 copies/mL), and 26% had detectable SARS-CoV-2 antibodies (IgA, IgM, IgG, and/or total Ig) at baseline. Infectious virus was recovered in 7% of participants with SARS-CoV-2 antibodies compared to 58% of participants without antibodies (probability ratio (PR)=0.12, 95% CI: 0.04, 0.36; p=0.00016). Infectious virus isolation was also associated with higher levels of viral RNA (mean RNA difference +2.6 log10, 95% CI: 2.2, 3.0; p<0.0001) and fewer days since symptom onset (PR=0.79, 95% CI: 0.71, 0.88 per day; p<0.0001).ConclusionsThe presence of SARS-CoV-2 antibodies is strongly associated with clearance of infectious virus isolation. Seropositivity and viral RNA levels are likely more reliable markers of infectious virus clearance than subjective measure of COVID-19 symptom duration. Virus-targeted treatment and prevention strategies should be administered as early as possible and ideally before seroconversion.Clinicaltrialsgov identifierNCT04405570.
| S-EPMC8183023 | biostudies-literature