Chuan Li1, Fengming Luo2, Chengwu Liu1, Nian Xiong3,4, Zhihua Xu5, Wei Zhang6,7, Ming Yang8, Ye Wang2, Dan Liu2, Chao Yu7,9, Jia Zeng7,10, Li Zhang11, Duo Li12, Yanbin Liu13, Mei Feng2, Ruoyang Liu14, Jiandong Mei1, Senyi Deng1, Zhen Zeng1, Yuanhong He15, Haiyan Liu16, Zhengyu Shi16, Meng Duan17, Deying Kang18, Jiayu Liao19,20, Weimin Li2, Lunxu Liu1. 1. Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China. 2. Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China. 3. Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 4. Wuhan Red Cross Hospital, Wuhan, China. 5. Department of Critical Care Medicine, Mianyang Central Hospital, Mianyang, China. 6. Department of Respiratory and Critical Care Medicine, First Affiliated Hospital, The Second Military Medical University, Shanghai, China. 7. Department of Infectious Diseases, Guanggu District, the Maternal and Child Health Hospital of Hubei Province, Wuhan, China. 8. Department of Respiratory Medicine, The Public Health Clinical Center of Chengdu, Chengdu, China. 9. Department of Respiratory and Critical Care Medicine, Naval Hospital of Eastern Theater of PLA, Zhoushan, China. 10. Department of Aviation Disease, Naval medical center of PLA, the Second Military Medical University, Shanghai, China. 11. Department of Respiratory Disease, Wuhan Red Cross Hospital, Wuhan, China. 12. Department of Respiratory Disease, The Affiliated Hospital of Southwest Medical University, Luzhou, China. 13. Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China. 14. Department of Respiratory Disease, Sichuan Second Hospital of T. C. M, Chengdu, China. 15. Department of Infectious Disease, The Public Health Clinical Center of Chengdu, Chengdu, China. 16. Department of Tuberculosis, The Public Health Clinical Center of Chengdu, Chengdu, China. 17. Department of Liver Disease, The Public Health Clinical Center of Chengdu, Chengdu, China. 18. Department of Evidence based Medicine and Clinical Epidemiology, West China Hospital, Sichuan University, Chengdu, China. 19. Department of Bioengineering, Bourns College of Engineering, University of California, Riverside, CA, USA. 20. The West China-California Research Center for Predictive Intervention Medicine, West China hospital, Sichuan University, Chengdu, China.
Abstract
BACKGROUND: There are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. To compare the effectiveness of a novel genetically engineered recombinant super-compound interferon (rSIFN-co) with traditional interferon-alpha added to baseline antiviral agents (lopinavir-ritonavir or umifenovir) for the treatment of moderate-to-severe COVID-19. METHOD: In this multicenter randomized (1:1) trial, patients hospitalized with moderate-to-severe COVID-19 received eitherrSIFN-co nebulization or interferon-alpha nebulization added to baseline antiviral agents for no more than 28 days. The primary endpoint was the time to clinical improvement. Secondary endpoints included the overall rate of clinical improvement assessed on day 28, the time to radiological improvement and virus nucleic acid negative conversion. RESULTS:A total of 94 patients were included in the safety set (46 patients assigned to rSIFN-co group, 48 to interferon-alpha group). The time to clinical improvement was 11.5 days versus 14.0 days (95% CI 1.10 to 2.81, p = .019); the overall rate of clinical improvement on day 28 was 93.5% versus 77.1% (difference, 16.4%; 95% CI 3% to 30%); the time to radiological improvement was 8.0 days versus 10.0 days (p = .002), the time to virus nucleic acid negative conversion was 7.0 days versus 10.0 days (p = .018) in the rSIFN-co and interferon alpha arms, respectively. Adverse events were balanced with no deaths among groups. CONCLUSIONS AND RELEVANCE: rSIFN-co was associated with a shorter time of clinical improvement than traditional interferon-alpha in the treatment of moderate-to-severe COVID-19 when combined with baseline antiviral agents. rSIFN-co therapy alone or combined with other antiviral therapy is worth to be further studied.Key messagesThere are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. Interferon alphas, by inducing both innate and adaptive immune responses, have shown clinical efficacy in treating severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus.In this multicenter, head-to-head, randomized, clinical trial which included 94 participants with moderate-to-severe COVID-19, the rSIFN-co plus antiviral agents (lopinavir-ritonavir or umifenovir) was associated with a shorter time of clinical improvement than interferon-alpha plus antiviral agents.
RCT Entities:
BACKGROUND: There are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. To compare the effectiveness of a novel genetically engineered recombinant super-compound interferon (rSIFN-co) with traditional interferon-alpha added to baseline antiviral agents (lopinavir-ritonavir or umifenovir) for the treatment of moderate-to-severe COVID-19. METHOD: In this multicenter randomized (1:1) trial, patients hospitalized with moderate-to-severe COVID-19 received either rSIFN-co nebulization or interferon-alpha nebulization added to baseline antiviral agents for no more than 28 days. The primary endpoint was the time to clinical improvement. Secondary endpoints included the overall rate of clinical improvement assessed on day 28, the time to radiological improvement and virus nucleic acid negative conversion. RESULTS: A total of 94 patients were included in the safety set (46 patients assigned to rSIFN-co group, 48 to interferon-alpha group). The time to clinical improvement was 11.5 days versus 14.0 days (95% CI 1.10 to 2.81, p = .019); the overall rate of clinical improvement on day 28 was 93.5% versus 77.1% (difference, 16.4%; 95% CI 3% to 30%); the time to radiological improvement was 8.0 days versus 10.0 days (p = .002), the time to virus nucleic acid negative conversion was 7.0 days versus 10.0 days (p = .018) in the rSIFN-co and interferon alpha arms, respectively. Adverse events were balanced with no deaths among groups. CONCLUSIONS AND RELEVANCE: rSIFN-co was associated with a shorter time of clinical improvement than traditional interferon-alpha in the treatment of moderate-to-severe COVID-19 when combined with baseline antiviral agents. rSIFN-co therapy alone or combined with other antiviral therapy is worth to be further studied.Key messagesThere are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. Interferon alphas, by inducing both innate and adaptive immune responses, have shown clinical efficacy in treating severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus.In this multicenter, head-to-head, randomized, clinical trial which included 94 participants with moderate-to-severe COVID-19, the rSIFN-co plus antiviral agents (lopinavir-ritonavir or umifenovir) was associated with a shorter time of clinical improvement than interferon-alpha plus antiviral agents.
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