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
Nomathemba Chandiwana, Chelsea Kruger, Hilary Johnstone, Mohamed Farouk Chughlay, Chung Ju, Byungsu Kim, Yengiwe Dineka, Sarah Arbe-Barnes, Robert Miller, Andrew Owen, Andrew Hill, Daniel Windgassen, Nada Abla, Anne Claire Marrast, Stephan Duparc, Willem Daniel Francois Venter
eBioMedicine, doi:10.1016/j.ebiom.2022.104322
Background This exploratory study investigated four repurposed anti-infective drug regimens in outpatients with COVID-19. Methods 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. Findings 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). Interpretation There was no statistical difference in viral clearance for any regimen compared to SOC. All treatments were well tolerated.
Appendix A. Supplementary data Supplementary data related to this article can be found at https://doi. org/10.1016/j.ebiom.2022.104322.
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