NCT04374019.

Methods	Trial design: open‐label RCT with 5 parallel arms, unclear which comparisons are planned; besides ivermectin, study arms include camostat mesilate, artemesia annua, and artesunate Type of record: trial register entry Sample size: 240 Setting: NR Country: USA Language: English Number of centres: 1 Study purpose (treatment, prevention): treatment Trial registration number: NCT04374019 Date of registration: 5 May 2020
Participants	Inclusion criteria Age ≥ 18 years Laboratory‐confirmed SARS‐CoV‐2 infection within the past 7 days or the presence of symptoms or physical examination signs providing high probability of COVID‐19 disease Must have adequate organ and marrow function measured within the last 6 months Must have ≥ 1 of the following high‐risk features or clinical deterioration: hypertension, diabetes mellitus, moderate‐to‐severe COPD, emphysema, cystic fibrosis, or asthma; people with cancer who have received any immunosuppressive drugs within 1 year from enrolment, sickle cell disease or thalassaemia, age ≥ 50 years, BMI ≥ 30 kg/m2, living in a nursing home or long‐term facility, underlying serious heart condition as determined by the treating physician, immunocompromized person as defined by the treating physician or COVID‐19 Telehealth Treatment Team Exclusion criteria Severe or life‐threatening COVID‐19 Weight < 45 kg Pregnant or breastfeeding women Receiving dialysis or with creatinine clearance < 45 mL/minute Existing Division of Microbiology and Infectious Diseases Toxicity Scale for Determining Severity of Adverse Events grade ≥ 3 hepatic failure Previously documented moderate or severe retinopathy or macular degeneration Uncontrolled seizure disorder Prolonged QT, defined as QTc ≥ 470 ms for men and QTc ≥ 480 ms for women using Bazett's formula Known allergy to artesunate, artemisia annua, hydroxychloroquine, macrolides, 4‐aminoquinolines, camostat mesilate, or other agents to be used in the trial Currently receiving any study medications for other indications Concurrent use of medication that would cause drug–drug interactions Psychiatric illness/social situations that would limit compliance
Interventions	Details of intervention for relevant arms Type and dose: ivermectin 12 mg total daily dose (< 75 kg) or 15 mg total daily dose (> 75 kg), for 2 days Route of administration: oral Treatment details of control group NR Concomitant therapy: NR
Outcomes	Primary study outcome Clinical deterioration at 14 days Relevant review outcomes planned Progression to ICU care or ventilation at 28 days Rate of severe adverse events at 14 days Additional study outcomes Mortality at 14 days Change in viral load at 40 days Rate of organ failure at 28 days Change in clinical status at 14 days Oxygen‐free days at 28 days Ventilator‐free days at 28 days ICU‐free days at 28 days Hospital‐free days at 28 days Participants meeting Hy's Law criteria at 28 days Liver function at 28 days Heart function at 28 days
Notes	Reason for awaiting classification: unclear control arm; unclear healthcare setting Recruitment status: recruiting Prospective completion date: May 2022, postponed from May 2021 Planned completion date more than 6 months ago: no Date last update posted: 30 June 2021 Sponsor/funding: Susanne Arnold