In a recent study published in JAMA, researchers evaluated the efficacy of low-dosage fluvoxamine (50 mg two times a day) over 10.0 days in the management of mild and moderate-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the United States (US).
The continual emergence of SARS-CoV-2 variants has challenged the efficacy of coronavirus disease 2019 (COVID-19) vaccines and other therapeutic options, such as monoclonal antibodies, warranting the development of novel orally administered agents for preventing the progression of SARS-CoV-2 infections.
The efficacy of fluvoxamine treatment to reduce symptom duration and prevent COVID-19 severity outcomes such as hospitalizations and deaths among individuals diagnosed with mild or moderate and symptomatic coronavirus disease 2019 (COVID-19) in outpatient settings is not clear.
About the study
In the present randomized clinical trial study, researchers tested repurposed medications in outpatient settings for mild or moderate SARS-CoV-2 infections that do not require hospitalization.
The ongoing ACTIV-6 (accelerating COVID-19 therapeutic interventions and vaccines) platform placebo-controlled and double-blind trial comprised 1,288 individuals aged ≥30.0 years with antigen test (including at-home testing) or polymerase chain reaction (PCR)-confirmed mild or moderate SARS-CoV-2 infection for ≤10.0 days, experiencing ≥2.0 acute SARS-CoV-2 infection symptoms for ≤1.0 week.
Symptoms included dyspnea, fatigue, fever, nausea, cough, diarrhea, vomiting, chills, body ache, sore throat, headaches, and loss of smell or taste. The study was conducted between 6 August 2021 and 27 May 2022 across 91 US sites, wherein the participants received 50.0 mg fluvoxamine two times a day for 10.0 days, 400 μg/kg oral ivermectin daily for three days, or 200 μg of inhaled fluticasone furoate daily for two weeks, or a placebo.
The prime outcome comprised the duration for sustained COVID-19 recovery (or the final day of three consecutive asymptomatic days). There were seven secondary study outcomes, inclusive of a composite study outcome comprising hospitalizations, urgent care visits, emergency department visits, or deaths within 28 days.
Secondary outcomes included the average duration of feeling sick and COVID-19 clinical progression scale scores after weeks 1.0, 2.0, and 4.0 of treatment. In addition, the participants filled out questionnaires for quality-of-life assessments.
Recruitment into the ACTIV-6 platform clinical trial commenced on 11 June 2021 and is under process. The team excluded individuals with contraindications for or allergies to fluvoxamine treatment. The drugs were provided to participants’ residential locations and were self-administered. Follow-up assessments were performed on day 28 and day 90 of treatment.
Regression models, including proportional hazards regression, were used for the analysis, and hazard ratios (HR) were calculated. Estimator variables included sex, age, symptom duration before receiving fluvoxamine, calendar time, the status of COVID-19 vaccination status, and place of residence.
A total of 1,331 individuals were randomized, with median participant age of 47 years, and most (57%) participants were female, 81% were Whites, and 67% were two-dose COVID-19 vaccine recipients. However, 1,288 individuals completed the clinical trial (674 and 614 fluvoxamine-treated and 614 placebo-treated individuals, respectively).
Out of 614 placebo-treated participants, 53% (n=326) were provided placebo drugs matching fluvoxamine, whereas 47% (n=288) received placebo medications matching inhaled fluticasone furoate or ivermectin. High-risk comorbid conditions were prevalent among the study participants, including elevated body mass index (BMI) > 30 (36%), hypertension (24%), asthma (13%), and diabetes (9.0%).
The median durations for sustained COVID-19 recovery were 12.0 days and 13.0 days for fluvoxamine-treated and placebo-treated individuals, respectively, with an HR value of 1.0. For the secondary composite study outcome, 26 fluvoxamine recipients were admitted to hospitals, hospitalized, required urgent care, visited the emergency department, or deceased, compared to 23 placebo recipients (HR value of 1.10).
One fluvoxamine-treated and two placebo-treated individuals required hospitalizations; however, no deaths were reported for any treatment groups. In addition, adverse events among both groups were comparable and not commonly observed in the two groups. The average difference in the duration of time spent feeling ill was 0.1 days, favoring placebo treatment.
Likewise, the posterior probability of benefits observed with the COVID-19 clinical progression scale at the defined time intervals could not meet thresholds for the beneficial treatment effects. E.g., within a week, 92% of fluvoxamine-treated and 93% of placebo-treated individuals did not require hospitalization and documented no limitations in performing regular activities.
No evidence was observed for fluvoxamine treatment effects compared to placebo for the status of COVID-19 vaccination, the onset of COVID-19 symptoms, symptom severity, sex, age, and calendar time. However, evidence for potential differences in treatment effects was observed for recovery duration for BMI, indicating an increase in fluvoxamine treatment benefit with an increase in BMI.
Overall, the study findings showed that among mild or moderate SARS-CoV-2 infection outpatients, 50.0 mg fluvoxamine therapy two times a day for 10.0 days, compared with placebo, showed no significant improvement in duration for sustained COVID-19 recovery. The findings do not support fluvoxamine administration in the aforementioned regimen for outpatients with mild or moderate SARS-CoV-2 infections.