Safety and efficacy of four drug regimens versus standard-of-care for the treatment of symptomatic outpatients with COVID-19: A randomised, open-label, multi-arm, phase 2 clinical trial


Chandiwana, Nomathemba, Kruger, Chelsea, Johnstone, Hilary, Chughlay, Mohamed Farouk, Ju, Chung, Kim, Byungsu, Dineka, Yengiwe, Arbe-Barnes, Sarah, Miller, Robert, Owen, Andrew ORCID: 0000-0002-9819-7651 et al (show 6 more authors) (2022) Safety and efficacy of four drug regimens versus standard-of-care for the treatment of symptomatic outpatients with COVID-19: A randomised, open-label, multi-arm, phase 2 clinical trial. EBIOMEDICINE, 86. 104322-.

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Abstract

<h4>Background</h4>This exploratory study investigated four repurposed anti-infective drug regimens in outpatients with COVID-19.<h4>Methods</h4>This phase 2, single centre, randomised, open-label, clinical trial was conducted in South Africa between 3rd September 2020 and 23rd August 2021. Symptomatic outpatients aged 18-65 years, with RT-PCR confirmed SARS-CoV-2 infection were computer randomised (1:1:1:1:1) to standard-of-care (SOC) with paracetamol, or SOC plus artesunate-amodiaquine (ASAQ), pyronaridine-artesunate (PA), favipiravir plus nitazoxanide (FPV + NTZ), or sofosbuvir-daclatasvir (SOF-DCV). The primary endpoint was the incidence of viral clearance, i.e., the proportion of patients with a negative SARS-CoV-2 RT-PCR on day 7, compared to SOC using a log-binomial model in the modified intention-to-treat (mITT) population.<h4>Findings</h4>The mITT population included 186 patients: mean age (SD) 34.9 (10.3) years, body weight 78.2 (17.1) kg. Day 7 SARS-CoV-2 clearance rates (n/N; risk ratio [95% CI]) were: SOC 34.2% (13/38), ASAQ 38.5% (15/39; 0.80 [0.44, 1.47]), PA 30.3% (10/33; 0.69 [0.37, 1.29]), FPV + NTZ 27.0% (10/37; 0.60 [0.31, 1.18]) and SOF-DCV 23.5% (8/34; 0.47 [0.22, 1.00]). Three lower respiratory tract infections occurred (PA 6.1% [2/33]; SOF-DCV 2.9% [1/34]); two required hospitalisation (PA, SOF-DCV). There were no deaths. Adverse events occurred in 55.3% (105/190) of patients, including one serious adverse event (pancytopenia; FPV + NTZ).<h4>Interpretation</h4>There was no statistical difference in viral clearance for any regimen compared to SOC. All treatments were well tolerated.<h4>Funding</h4>Medicines for Malaria Venture, with funding from the UK Foreign, Commonwealth and Development Office, within the Covid-19 Therapeutics Accelerator in partnership with Wellcome, the Bill and Melinda Gates Foundation, and Mastercard.

Item Type: Article
Uncontrolled Keywords: SARS-CoV-2, Pyronaridine-artesunate, Artesunate-amodiaquine, Favipiravir + nitazoxanide Sofosbuvir-daclatasvir, Outpatient
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 28 Mar 2023 14:52
Last Modified: 28 Mar 2023 14:52
DOI: 10.1016/j.ebiom.2022.104322
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3169323
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