Efficacy of Niclosamide vs Placebo in SARS-CoV-2 Respiratory Viral Clearance, Viral Shedding, and Duration of Symptoms Among Patients With Mild to Moderate COVID-19
PhD Dana M Cairns, PhD Dorothy Dulko, MD, MPHTM Jeffrey K Griffiths, MD, MS Yoav Golan, PhD Theodora Cohen, PhD, MS, MPH Ludovic Trinquart, MAS Lori Lyn Price, PharmD, BCIDP Kirthana R Beaulac, MD, MSPH Harry P Selker
JAMA Network Open, doi:10.1001/jamanetworkopen.2021.44942
IMPORTANCE Oral anthelmintic niclosamide has potent in vitro antiviral activity against SARS-CoV-2. Repurposed niclosamide could be a safe and efficacious COVID-19 therapy. OBJECTIVE To investigate whether niclosamide decreased SARS-CoV-2 shedding and duration of symptoms among patients with mild to moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS This randomized, placebo-controlled clinical trial enrolled individuals testing positive for SARS-CoV-2 by polymerase chain reaction with mild to moderate symptoms of COVID. All trial participants, investigators, staff, and laboratory personnel were kept blind to participant assignments. Enrollment was among individuals reporting at Tufts Medical Center and Wellforce Network in Massachusetts for outpatient COVID-19 testing. The trial opened to accrual on October 1, 2020; the last participant enrolled on April 20, 2021. Trial exclusion criteria included hospitalization at time of enrollment or use of any experimental treatment for COVID-19, including vaccination. Enrollment was stopped before attaining the planned sample size when COVID-19 diagnoses decreased precipitously in Massachusetts. Data were analyzed from July through September 2021. INTERVENTIONS In addition to receiving current standard of care, participants were randomly assigned on a 1:1 basis to receive niclosamide 2 g by mouth daily for 7 days or identically labeled placebo at the same dosing schedule.
MAIN OUTCOMES AND MEASURES Oropharyngeal and fecal samples were self-collected for viral shedding measured by reverse-transcriptase-polymerase-chain-reaction on days 3, 7, 10, and 14, and an additional fecal sample was collected on day 21. A telehealth platform was developed to conduct remote study visits, monitor symptoms, and coordinate sample collection via couriers. The primary end point was the proportion of participants with viral clearance in respiratory samples at day 3 based on the intention-to-treat sample. Mean times to viral clearance and symptom resolution were calculated as restricted mean survival times and accounted for censored observations. RESULTS Among 73 participants, 36 individuals were enrolled and randomized to niclosamide and 37 individuals to placebo. Participant characteristics were similar across treatment groups; among 34 patients receiving placebo and 33 patients receiving niclosamide in the intention-to-treat sample, mean (SD) age was 36.0 (13.3) years vs 36.8 (12.9) years and there were 21 (61.8%) men vs 20 (60.6%) men. The overall mean (SD) age was 36.4 (13.0) years. For the primary end point, 66.67% (95% CI, 50.74% to 81.81%) of participants receiving niclosamide and 55.88% (95% CI, 40.27% to (continued) Key Points Question Does oral niclosamide decrease the contagious period as determined by SARS-CoV-2 shedding among patients with mild to moderate COVID-19? Findings In this randomized clinical trial that included 73 adults with mild to moderate COVID-19, the proportion of participants achieving..
Conflict of Interest Disclosures: Dr Golan reported receiving personal fees from Pfizer, Merck, and Appili Therapeutics outside the submitted work. Dr Beaulac reported receiving personal fees from Astellas Pharma and Allergan-AbbVie and grants from Diatherix outside the submitted work. No other disclosures were reported.
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