NCT04712279.

Study name	The (HD)IVACOV Trial (The High‐Dose IVermectin Against COVID‐19 Trial)
Methods	Trial design: triple‐blind RCT with 3 parallel arms Type of record: trial register entry Sample size: 294 Setting: outpatient Country: Brazil Language: English Number of centres: NR Study purpose (treatment, prevention): treatment Trial registration number: NCT04712279 Date of registration: 15 January 2021
Participants	Inclusion criteria Age ≥ 18 years Laboratory‐confirmed positive SARS‐CoV‐2 RT‐PCR test within 7 days prior to randomization Clinical status on the COVID‐19 Ordinal Scale 1–3 Participant (or legally authorized representative) gives written informed consent prior to performing any study procedures Participant (or legally authorized representative) agree that they will not participate in another COVID‐19 trial during this study Exclusion criteria Enrolled in a study to investigate a treatment for COVID‐19 Require oxygen use, hospitalization, or mechanical ventilation Tachycardia (heart rate > 150 beats/min) or hypotension (systolic/diastolic blood pressure < 90/60 mmHg) Allergic to the investigational product or similar drugs (or any excipients) QTcF > 450 ms Uncontrolled medical conditions that could compromise participation in the study – uncontrolled hypertension (systolic/diastolic blood pressure > 220/120 mmHg), uncontrolled hypothyroidism (thyroid‐stimulating hormone > 10 IU/L), uncontrolled diabetes mellitus (glycosylated haemoglobin > 12%) ALT or AST > 5 times ULN Estimated GFR < 30 mL/min or requiring dialysis Person (or legally authorized representative) unwilling or unable to provide informed consent
Interventions	Details of intervention Type and dose Intervention 1: ivermectin 0.6 mg/kg, once daily for 5 days Intervention 2: ivermectin 1 mg/kg, once daily for 5 days Route of administration: NR Treatment details of control group Placebo Concomitant therapy: standard of care (hydroxychloroquine) administered in both study arms
Outcomes	Primary study outcome WHO Clinical Progression Scale at 14 days Relevant review outcomes planned WHO Clinical Progression Scale at 14 days WHO COVID‐19 Ordinal Scale for Clinical Improvement at 7 days Proportion of hospitalizations at 28 days Time‐to‐recovery within 28 days Proportion of deaths at 28 days Proportion of hospitalizations Additional study outcomes WHO COVID‐19 Ordinal Scale for Clinical Improvement at 7 days Proportion of participants needing oxygen use within 28 days Proportion of participants needing high‐flow oxygen therapy or non‐invasive ventilation within 28 days Proportion of hospitalizations at 28 days Proportion of mechanical ventilation use at 28 days Duration of hospitalization within 28 days Time‐to‐recovery within 28 days Viral load at 5 days Positivity rate of RT‐PCR SARS‐CoV‐2 (qualitative analysis) at 5 days Duration of fatigue, ansomia within 14 days Duration of clinical manifestations within 14 days Proportion of participants needing additional drugs or interventions within 28 days Proportion of subjects needing oxygen use Proportion of hospitalizations Duration of mechanical ventilation within 28 days Proportion of vasopressor use at 28 days Proportion of deaths at 28 days Proportion of post‐COVID mental, physical, and overall symptoms at 30, 60, and 90 days Duration of new oxygen use within 28 days Duration of hospitalization Proportion of increased ultrasensitive CRP, ESR, eosinophils at 1, 3, and 7 days Proportion of increased D‐dimer at 7 days Disease duration
Starting date	25 January 2021
Contact information	Flavio A Cadegiani, MD, PhD Corpometria Institute +55 61 99650.6111 flavio.cadegiani@gmail.com
Notes	Recruitment status: not yet recruiting Prospective completion date: April 2021 Planned completion date more than 6 months ago: yes Date last update posted: 15 January 2021 Sponsor/funding: Corpometria Institute