López‐Medina 2021.

Study characteristics
Methods	Trial design: double‐blind RCT with 2 parallel arms Type of publication: journal publication Setting: outpatient (< 1% inpatients at baseline) Recruitment dates: July to December 2020 Country: Columbia Language: English Number of centres: 1 Study purpose (treatment, prevention): treatment Trial registration number: NCT04405843 Date of registration: 28 May 2020
Participants	Number of participants (randomized/analyzed): 476/398 Age (median): overall 37 years Males, n: overall 167 (42%) Severity of condition according to study definition: mild disease, defined as being at home or hospitalized but not receiving high‐flow nasal oxygen or mechanical ventilation Severity of condition according to WHO scale: 2 to 3 (< 1% of included patients 4 to 5) Co‐morbidities: any pre‐existing condition, obesity, diabetes, hypertension, respiratory disease Virus detection performed at baseline (test‐positive at baseline): RT‐PCR or rapid antigen test (100%) Inclusion criteria: aged ≥ 18 years; confirmed SARS‐CoV‐2 by RT‐PCR or antigen detection in a Colombian NIH‐approved laboratory; beginning of symptoms in the past 7 days; mild disease; informed consent Exclusion criteria: pre‐existing liver disease; hypersensitivity to ivermectin; participants in other clinical trials for therapies against COVID‐19; severe pneumonia; pregnant or breastfeeding women; concomitant use of warfarin, erdafitinib, or quinidine; use of ivermectin in the 5 days prior to randomization; inability to obtain a blood sample needed to assess liver transaminases; elevation of transaminases > 1.5 times the normal level; participant whose first contact with the study personnel occurs between days 5 and 7 and at that time manifests significant and progressive resolution of COVID‐19 related signs and symptoms
Interventions	Details of intervention Type and dose: ivermectin 0.3 mg/kg, once daily for 5 days Route of administration: oral Treatment details of control group Placebo with standard of care Up to 26 August 2020, the placebo was a mixture of 5% dextrose in saline and 5% dextrose in distilled water, after which placebo was a solution with similar organoleptic properties to ivermectin Concomitant therapy: standard of care including NSAIDs, antipyretic drugs, antibiotics, steroids, anticoagulants administered in both study arms Duration of follow‐up: 21 days Treatment cross‐overs: none
Outcomes	Primary study outcome Time to resolution of symptoms (hazard ratio) Symptom resolution at 21 days Relevant review outcomes reported Mortality at 21 days Worsening of clinical status – need for invasive mechanical ventilation at 15 days Worsening of clinical status – need for non‐invasive mechanical ventilation or high flow at 15 days Symptom resolution at 15 days Duration to symptom resolution, reported as median Adverse events within 21 days Serious adverse events within 21 days Additional study outcomes reported Deterioration of ≥ 2 points in an ordinal 8‐point scale Overall number of participants hospitalized with or without supplemental oxygen (could not be judged as either worsening or improvement due to overlap with status at baseline) Fever since randomization Median duration of febrile episode Emergency department visits or telemedicine consultations, number of participants Escalation of care since randomization and escalation of care occurring ≥ 12 hours since randomization including mortality at 15 days worsening of clinical status – need for invasive mechanical ventilation at 21 days worsening of clinical status – need for non‐invasive mechanical ventilation or high flow at 21 days
Notes	Date of publication: 4 March 2021 Sponsor/funding: Centro de Estudios en Infectología Pediátrica Information on ethics votum: name of responsible ethics committee, reference number of proposal, and votum reported