Efficacy and Safety of Triazavirin Therapy for Coronavirus Disease 2019: A Pilot Randomized Controlled Trial
Xiaoke Wu,
Kaijiang Yu,
Yongchen Wang,
Wanhai Xu,
Hongli Ma,
Yan Hou,
Yue Li,
Benzhi Cai,
Liying Zhu,
Min Zhang,
Xiaoli Hu,
Jingshu Gao,
Yu Wang,
Huichao Qin,
Wenjie Wang,
Mingyan Zhao,
Xia Wu,
Yong Zhang,
Lu Li,
Kang Li,
Zhimin Du,
Ben Willem J. Mol,
Baofeng Yang
Affiliations
Xiaoke Wu
College of Pharmacology, Harbin Medical University, Harbin 150001, China; Heilongjiang Provincial Hospital, Harbin Institute of Technology, Harbin 150030, China; First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin 150040, China
Kaijiang Yu
First Affiliated Hospital, Harbin Medical University, Harbin 150001, China
Yongchen Wang
Second Affiliated Hospital, Harbin Medical University, Harbin 150001, China
Wanhai Xu
Fourth Affiliated Hospital, Harbin Medical University, Harbin 150001, China
Hongli Ma
First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin 150040, China
Yan Hou
College of Pharmacology, Harbin Medical University, Harbin 150001, China
Yue Li
First Affiliated Hospital, Harbin Medical University, Harbin 150001, China
Benzhi Cai
Second Affiliated Hospital, Harbin Medical University, Harbin 150001, China
Liying Zhu
Fourth Affiliated Hospital, Harbin Medical University, Harbin 150001, China
Min Zhang
Heilongjiang Provincial Hospital, Harbin Institute of Technology, Harbin 150030, China
Xiaoli Hu
Heilongjiang Provincial Hospital, Harbin Institute of Technology, Harbin 150030, China
Jingshu Gao
First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin 150040, China
Yu Wang
First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin 150040, China
Huichao Qin
First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin 150040, China
Wenjie Wang
College of Pharmacology, Harbin Medical University, Harbin 150001, China
Mingyan Zhao
First Affiliated Hospital, Harbin Medical University, Harbin 150001, China
Xia Wu
Second Affiliated Hospital, Harbin Medical University, Harbin 150001, China
Yong Zhang
College of Pharmacology, Harbin Medical University, Harbin 150001, China
Lu Li
College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China
Kang Li
College of Pharmacology, Harbin Medical University, Harbin 150001, China
Zhimin Du
Second Affiliated Hospital, Harbin Medical University, Harbin 150001, China
Ben Willem J. Mol
Monash Medical Centre, Monash University, Melbourne, VIC 3800, Australia
Baofeng Yang
College of Pharmacology, Harbin Medical University, Harbin 150001, China; Corresponding author.
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% versus 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.
