Efficacy and Safety of Triazavirin Therapy for Coronavirus Disease 2019: A Pilot Randomized Controlled Trial

Abstract

No therapeutics have been proven effective yet for the treatment of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To assess the efficacy and safety of Triazavirin therapy for COVID-19, we conducted a randomized, double-blinded controlled trial involving hospitalized adult patients with COVID-19. Participants were enrolled from ten sites, and were randomized into two arms of the study with a ratio of 1:1. Patients were treated with Triazavirin 250 mg versus a placebo three or four times a day for 7 d. The primary outcome was set as the time to clinical improvement, defined as normalization of body temperature, respiratory rate, oxygen saturation, cough, and absorption of pulmonary infection by chest computed tomography (CT) until 28 d after randomization. Secondary outcomes included individual components of the primary outcome, the mean time and proportion of inflammatory absorption in the lung, and the conversion rate to a repeated negative SARS-CoV-2 nucleic acid test of throat swab sampling. Concomitant therapeutic treatments, adverse events, and serious adverse events were recorded. Our study was halted after the recruitment of 52 patients, since the number of new infections in the participating hospitals decreased greatly. We randomized 52 patients for treatment with Triazavirin ( n = 26) or a placebo ( n = 26). We found no differences in the time to clinical improvement (median, 7 d versus 12 d; risk ratio (RR), 2.0; 95% confidence interval (CI), 0.7–5.6; p = 0.2), with clinical improvement occurring in ten patients in the Triazavirin group and six patients in the placebo group (38.5% vs. 23.1%, RR, 2.1; 95% CI, 0.6–7.0; p = 0.2). All components of the primary outcome normalized within 28 d, with the exception of absorption of pulmonary infection (Triazavirin 50.0%, placebo 26.1%). Patients in the Triazavirin group used less frequent concomitant therapies for respiratory, cardiac, renal, hepatic, or coagulation supports. Although no statistically significant evidence was found to indicate that Triazavirin benefits COVID-19 patients, our observations indicated possible benefits from its use to treat COVID-19 due to its antiviral effects. Further study is required for confirmation.

Systematic Review on the Therapeutic Options for COVID-19: Clinical Evidence of Drug Efficacy and Implications

“…Triazavirin acts via inhibition of RNA-dependent RNA polymerase enzyme, thereby inhibiting viral RNA synthesis. 132 In their study, Wu et al (2020) found that patients administered triazavirin required fewer respiratory, cardiac, hepatic, or renal support therapies than the control group. 132 However, despite the possible benefit observed, a large randomized, controlled clinical trial is needed before the place of triazavirin can be determined in COVID-19 patients.…”

“…Favipiravir 1600 mg twice on day 1, then 600 mg twice daily for 10-days 2. Umefovir 200 mg three times daily for 7-days FVR compared to Umifenovir did not significantly improve the patient’s recovery Chen et al, 2020 128 ChiCTR20000300001 52 Hospitalized patients with moderate COVID-19 Triazavirin A Pilot Randomized Multicenter Controlled Clinical Trial Triazavirin 250 mg versus a placebo three or four times a day for 7- days Triazavirin group required Fewer therapies for respiratory, cardiac, renal, hepatic, or coagulation supports Wu et al, 2020 132 NCT04315480 100 Hospitalized patients with severe COVID-19 TCZ Off-Label, Non-Randomized, Single-Center Study TCZ 8mg/Kg twice daily IV TCZ significantly reduced the need for mechanical ventilation, duration of hospital stays Toniati et al, 2020 150 63 Hospitalized patients with severe COVID-19 TCZ A Prospective Open, Single-Arm Multicentre Trial TCZ 8 mg/Kg IV or 324 mg SC TCZ improve respiration in a patient with severe COVID-19 Sciascia et al, 2020 151 NCT04346355 126 Hospitalized patients with severe COVID-19 TCZ Prospective, Open-Label, Randomized Clinical Trial TCZ 8 mg/Kg up to a maximum of 800 mg IV TCZ did not improve disease progression compared with standard care Salvarani et al, 2020 169 EudraCT 2020–001934-37 85 Hospitalized patients with severe COVID-19 Methylprednisolone Partially Randomized, Open-Label, Multicenter Controlled Trial 400 mg twice daily for 3-days, then 20 mg twice daily for 3-day...…”

Reviews on Biological Activity, Clinical Trial and Synthesis Progress of Small Molecules for the Treatment of COVID-19

“…The results showed that Favipiravir did not have any dramatic efficiency against COVID-19 even at high concentration. Cai et al [ 117 ] conducted an Open-Label Controlled trial to test the efficacy of Favipiravir compared to Lopinavir (LPV)/Ritonavir (RTV) as anti-COVID-19 agents. Patients were randomly allocated to Favipiravir group (dose 1.6 g twice a day for the 1st day; dose 0.6 g twice a day for 2–14 days) and LPV/RTV group (dose 0.4 g/0.1 g twice a day); the results showed that the Favipiravir group patients exhibited higher efficacy than the LPV/RTV group.…”

COVID-19: Before the Fall, An Evidence-Based Narrative Review of Treatment Options

“…Favipiravir and umifenovir are broad antivirals approved in countries outside the USA that were used as anti-influenza agents. Both drugs have had limited clinical data supporting their use, although there has been some in vitro data [ 40 , 42 , 95 , 96 ]. Sofosbuvir/daclatasvir is a treatment for hepatitis C infection that has also been found to bind to SARS-CoV-2 [ 97 ].…”