TOGETHER‐3.

Methods	Drug name: lopinavir ritonavir, ascorbic acid Trial design: parallel, randomised, blinded trial Identifier: PACTR202007700757139 Target sample size: 420 participants Planned completion date: July 2021
Participants	Setting Outpatient Single‐centre, South Africa Eligibility criteria Inclusion criteria Men or women 18 to 80 years, inclusive, at the time of signing the informed consent Willing and able to provide informed consent Laboratory‐confirmed SARS‐CoV‐2 infection, with test results within past 72 hours At increased risk of developing severe COVID‐19 disease Exclusion criteria Known hypersensitivity to any of the study drugs Currently hospitalised Signs of respiratory distress prior to randomisation, including respiratory rate > 24 breath/minute and/or SpO2 < 93% Chronic kidney disease (stage IV or receiving dialysis) Known liver disease or cirrhosis Known personal or family history of long QT syndrome Taking chronic medications associated with prolonged QT and may induce Torsades de Pointes as per CredibleMeds.org, including certain antipsychotic medications or antidepressants (e.g. citalopram, venlafaxine, and bupropion) and unable to stop during the trial Baseline QTc interval of > 470 ms in men, and > 480 ms in women if indicated by the safety profile of the investigational product Potentially clinically significant pharmacokinetic and pharmacodynamic drug interactions as determined by the study clinical pharmacologist Currently participating in a clinical trial currently or within 30 days of randomisation
Interventions	Intervention Lopinavir ritonavir Comparator Ascorbic acid
Outcomes	Efficacy outcomes: All‐cause mortality at up to 30 days: not planned 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: planned Safety outcomes Number of participants with grade 3 and grade 4 AEs: not planned Number of participants with SAEs: planned Additional study outcomes Lower respiratory tract infection, defined by SpO2 < 93% or decline from baseline of 6% in 2 measurements at least 2 hours apart
Notes	Funding: University of Washington