2020, Volume 6, Issue 10
Engineering >> 2020, Volume 6, Issue 10 doi: 10.1016/j.eng.2020.08.011
Efficacy and Safety of Triazavirin Therapy for Coronavirus Disease 2019: A Pilot Randomized Controlled Trial
a College of Pharmacology, Harbin Medical University, Harbin 150001, China
b Heilongjiang Provincial Hospital, Harbin Institute of Technology, Harbin 150030, China
c First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin 150040, China
d First Affiliated Hospital, Harbin Medical University, Harbin 150001, China
e Second Affiliated Hospital, Harbin Medical University, Harbin 150001, China
f Fourth Affiliated Hospital, Harbin Medical University, Harbin 150001, China
g College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China
h Monash Medical Centre, Monash University, Melbourne, VIC 3800, Australia
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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% 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.
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References
[ 1 ] Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395 (10223):497–506. link1
[ 2 ] Wang T, Du Z, Zhu F, Cao Z, An Y, Gao Y, et al. Comorbidities and multi-organ injuries in the treatment of COVID-19. Lancet 2020;395(10228): e52. link1
[ 3 ] Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA 2020;323(13):1239–42. link1
[ 4 ] National Health Commission of the People’s Republic of China, National Administration of Traditional Chinese Medicine. Diagnosis and treatment protocol for novel coronavirus pneumonia (trial version 7). Chin Med J 2020;133:1087–95.
[ 5 ] Kalil AC. Treating COVID-19-off-label drug use, compassionate use, and randomized clinical trials during pandemics. JAMA 2020;323(19):1897–8. link1
[ 6 ] Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A trial of Lopinavir– Ritonavir in adults hospitalized with severe COVID-19. N Engl J Med 2020;382 (19):1787–99. link1
[ 7 ] Karpenko I, Deev S, Kiselev O, Charushin V, Rusinov V, Ulomsky E, et al. Antiviral properties, metabolism, and pharmacokinetics of a novel azolo-1,2,4- triazine-derived inhibitor of influenza A and B virus replication. Antimicrob Agents Chemother 2010;54(5):2017–22. link1
[ 8 ] Loginova SI, Borisevich SV, Rusinov VL, Ulomskiĭ UN, Charushin VN, Chupakhin ON. Investigation of Triazavirin antiviral activity against tick-borne encephalitis pathogen in cell culture. Antibiot Khimioter 2014;59(1–2):3–5. Russian. link1
[ 9 ] Loginova SY, Borisevich SV, Rusinov VL, Ulomsky UN, Charushin VN, Chupakhin N, et al. Investigation of prophylactic efficacy of Triazavirin against experimental forest-spring encephalitis on albino mice. Antibiot Khimioter 2015;60(5–6):8–11. Russian. link1
[10] Kiselev OI, Deeva EG, Mel’nikova TI, Kozeletskaia KN, Kiselev AS, Rusinov VL, et al. A new antiviral drug Triazavirin: results of phase II clinical trial. Vopr Virusol 2012;57(6):9–12. Russian. link1
[11] Wu X, Yu K, Wang Y, Xu W, Ma H, Hou Y, et al. The efficacy and safety of Triazavirin for COVID-19: a trial protocol. Engineering 2020;6(10):1199–204. link1
[12] National Health Commission of the People’s Republic of China, State Administration of Traditional Chinese Medicine. Diagnosis and treatment protocol for novel coronavirus pneumonia (trial version 7) [Internet]. Beijing: National Health Commission of the People’s Republic of China; [updated 2020 Mar 3; cited 2020 April 20]. Available from: http://www.nhc.gov.cn/xcs/ zhengcwj/202003/46c9294a7dfe4cef80dc7f5912eb1989.shtml. Chinese.
[13] Inciardi RM, Lupi L, Zaccone G, Italia L, Raffo M, Tomasoni D, et al. Cardiac involvement in a patient with coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020;5(7):819. link1
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