ANTICOV.

Methods	Drug name: lopinavir plus ritonavir, hydroxychloroquine Trial design: randomised, adaptive platform trial, open‐label study Identifiers: PACTR202006537901307 Target sample size: 3000 participants Planned completion date: December 2021
Participants	Setting Outpatient Multicentre, South Africa, Africa Eligibility criteria Inclusion criteria Male or female patients Adults ≥ 18 years of age at the time of screening. Children > 12 years of age may be included if recommended by the DSMB after the first analysis COVID‐19 confirmed by molecular biology for SARS‐Cov‐2 according to national guidelines, based on result within 24 hours prior to screening Viral syndrome with or without uncomplicated pneumonia, defined as SpO2 ≥ 94% Corrected QT interval (QTc ‐ Fridericia) < 480 msec on ECG Signed written consent from the patient or LAR Accepting and having the ability to be reached by telephone throughout the study Having designated a contact person who can be contacted in case of emergency Exclusion criteria: Abnormal physical examination findings Known glucose‐6‐phosphate dehydrogenase (G6PD) deficiency Feeling unwell for > 7 days prior to screening Severe cardiopathy or history of arrhythmia, renal or liver insufficiency History of congenital or acquired long QT‐interval, family history of long QT arrythmia, cardiac disease such as heart failure, myocardial infarction, family history of sudden cardiac death, sudden cardiac death, bradycardia < 50 bpm Past history of retinopathy, such as spots or dark strings floating in the field of vision (floaters), blurred or fluctuating vision, impaired colour vision, dark or empty areas in vision History of severe skin reactions such as Stevens‐Johnson syndrome and toxic epidermal necrolysis End‐organ compromise requiring admission to a resuscitation or continuous care unit or short‐term life‐threatening comorbidity with life expectancy < 3 months Known pregnancy or breastfeeding, unless recommended by the Data and Safety Monitoring Board after the first interim analysis Prior treatment with lopinavir/ritonavir within 29 days prior to screening except if patients are receiving the same regimen as planned in this study Prior treatment with hydroxychloroquine within 29 days prior to screening or ongoing at screening Use of concomitant medications that are contraindicated
Interventions	Intervention Lopinavir + ritonavir (opinavir 800 mg/ritonavir 200 mg; daily intake, oral) Hydroxychloroquine (800 mg and 400 mg, daily‐loading dose of 800 mg day 2‐7: maintenance dose of 400 mg daily, oral) Comparator: Paracetamol (dose: max 3g/day, oral route)
Outcomes	Efficacy outcomes All‐cause mortality at up to 30 days: planned (up to 21 days) at up to 60 days: not planned Clinical progression/improvement of symptoms: not planned Admission to hospital (for outpatients only): planned Length of hospital stay (for those admitted to hospital): not planned Admission to ICU: not planned Length of ICU stay: not planned Quality of life, including fatigue: not planned Viral clearance: not planned Safety outcomes Number of participants with grade 3 and grade 4 AEs: not planned Number of participants with SAEs: planned Additional study outcomes Disease‐free status Failure rate for each study arm
Notes	Funding: DNDi, Switzerland