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Head-to-head comparison of azvudine and nirmatrelvir/ritonavir for the hospitalized patients with COVID-19: a real-world retrospective cohort study with propensity score matching

Wei et al., Frontiers in Pharmacology, doi:10.3389/fphar.2023.1274294
Oct 2023  
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Mortality -0% Improvement Relative Risk Ventilation 28% ICU admission 55% Progression 22% primary Azvudine for COVID-19  Wei et al.  LATE TREATMENT Is late treatment with azvudine beneficial for COVID-19? Retrospective 725 patients in China (December 2022 - January 2023) Study compares with paxlovid, results vs. placebo may differ Lower ventilation with azvudine (p=0.039) c19early.org Wei et al., Frontiers in Pharmacology, Oct 2023 Favorsazvudine Favorspaxlovid 0 0.5 1 1.5 2+
Azvudine for COVID-19
44th treatment shown to reduce risk in July 2023, now with p = 0.000000082 from 31 studies.
Lower risk for mortality, progression, and viral clearance.
No treatment is 100% effective. Protocols combine treatments.
5,300+ studies for 116 treatments. c19early.org
PSM retrospective 725 hospitalized COVID-19 patients in China compared the effectiveness and safety of the oral antivirals azvudine and paxlovid. There was no significant difference in the risk of disease progression between groups, but azvudine was associated with lower ICU admission and invasive ventilation use.
Standard of Care (SOC): SOC for COVID-19 in the study country, China, is average with moderate average efficacy for approved treatments1.
Study covers paxlovid and azvudine.
risk of death, 0.2% higher, RR 1.00, p = 1.00, treatment 63 of 461 (13.7%), control 36 of 264 (13.6%).
risk of mechanical ventilation, 27.7% lower, RR 0.72, p = 0.04, treatment 77 of 461 (16.7%), control 61 of 264 (23.1%), NNT 16.
risk of ICU admission, 55.0% lower, RR 0.45, p = 0.05, treatment 11 of 461 (2.4%), control 14 of 264 (5.3%), NNT 34.
risk of progression, 22.1% lower, RR 0.78, p = 0.07, treatment 98 of 461 (21.3%), control 72 of 264 (27.3%), NNT 17, ICU admission, invasive mechanical ventilation, and in-hospital death, primary outcome.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Wei et al., 13 Oct 2023, retrospective, China, peer-reviewed, 8 authors, study period 1 December, 2022 - 31 January, 2023, this trial compares with another treatment - results may be better when compared to placebo. Contact: 13620327@qq.com, ld_2069@163.com.
This PaperAzvudineAll
Head-to-head comparison of azvudine and nirmatrelvir/ritonavir for the hospitalized patients with COVID-19: a real-world retrospective cohort study with propensity score matching
An-Hua Wei, Lu Zeng, Lu Wang, Lin Gui, Wen-Ting Zhang, Xue-Peng Gong, Juan Li, Dong Liu
Frontiers in Pharmacology, doi:10.3389/fphar.2023.1274294
Background: Nirmatrelvir/ritonavir and azvudine have been approved for the early treatment of COVID-19 in China, however, limited real-world data exists regarding their effectiveness and safety. Methods: We conducted a retrospective cohort study involving the hospitalized COVID-19 patients in China between December 2022 and January 2023. Demographic, clinical, and safety variables were recorded. Results: Among the 6,616 hospitalized COVID-19 patients, we included a total of 725 patients including azvudine recipients (N = 461) and nirmatrelvir/ritonavir (N = 264) recipients after exclusions and propensity score matching (1:2). There was no significant difference in the composite disease progression events between azvudine (98, 21.26%) and nirmatrelvir/ritonavir (72, 27.27%) groups (p = 0.066). Azvudine was associated with a significant reduction in secondary outcomes, including the percentage of intensive care unit admission (p = 0.038) and the need for invasive mechanical ventilation (p = 0.035), while the in-hospital death event did not significantly differ (p = 0.991). As for safety outcomes, 33 out of 461 patients (7.16%) in azvudine group and 22 out of 264 patients (8.33%) in nirmatrelvir/ritonavir group experienced drug-related adverse events between the day of admission (p = 0.565). Conclusion: In our real-world setting, azvudine treatment demonstrated similar safety compared to nirmatrelvir/ritonavir in hospitalized COVID-19 patients. Additionally, it showed slightly better clinical benefits in this population. However, further confirmation through additional clinical trials is necessary.
Ethics statement The studies involving humans were approved by the institutional review board of Tongji hospital (TJ-IRB20230202). The studies were conducted in accordance with the local legislation and institutional requirements. The ethics committee/institutional review board waived the requirement of written informed consent for participation from the participants or the participants' legal guardians/next of kin because Surveys and observational study. Author contributions A-HW: Conceptualization, Data curation, Formal Analysis, Investigation, Methodology, Writing-original draft, Writing-review and editing. LZ: Data curation, Formal Analysis, Methodology, Writing-review and editing. LW: Formal Analysis, Methodology, Writing-original draft. LG: Investigation, Writing-review and editing. W-TZ: Investigation, Project administration, Writing-review and editing. X-PG: Project administration, Writing-review and editing. JL: Supervision, Writing-review and editing. DL: Supervision, Writing-review and editing. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their Supplementary material The Supplementary Material for this article can be found online at:..
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DOI record: { "DOI": "10.3389/fphar.2023.1274294", "ISSN": [ "1663-9812" ], "URL": "http://dx.doi.org/10.3389/fphar.2023.1274294", "abstract": "<jats:p><jats:bold>Background:</jats:bold> Nirmatrelvir/ritonavir and azvudine have been approved for the early treatment of COVID-19 in China, however, limited real-world data exists regarding their effectiveness and safety.</jats:p><jats:p><jats:bold>Methods:</jats:bold> We conducted a retrospective cohort study involving the hospitalized COVID-19 patients in China between December 2022 and January 2023. Demographic, clinical, and safety variables were recorded.</jats:p><jats:p><jats:bold>Results:</jats:bold> Among the 6,616 hospitalized COVID-19 patients, we included a total of 725 patients including azvudine recipients (N = 461) and nirmatrelvir/ritonavir (N = 264) recipients after exclusions and propensity score matching (1:2). There was no significant difference in the composite disease progression events between azvudine (98, 21.26%) and nirmatrelvir/ritonavir (72, 27.27%) groups (<jats:italic>p</jats:italic> = 0.066). Azvudine was associated with a significant reduction in secondary outcomes, including the percentage of intensive care unit admission (<jats:italic>p</jats:italic> = 0.038) and the need for invasive mechanical ventilation (<jats:italic>p</jats:italic> = 0.035), while the in-hospital death event did not significantly differ (<jats:italic>p</jats:italic> = 0.991). As for safety outcomes, 33 out of 461 patients (7.16%) in azvudine group and 22 out of 264 patients (8.33%) in nirmatrelvir/ritonavir group experienced drug-related adverse events between the day of admission (<jats:italic>p</jats:italic> = 0.565).</jats:p><jats:p><jats:bold>Conclusion:</jats:bold> In our real-world setting, azvudine treatment demonstrated similar safety compared to nirmatrelvir/ritonavir in hospitalized COVID-19 patients. Additionally, it showed slightly better clinical benefits in this population. 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Infect.", "key": "B6", "volume": "86", "year": "2023" }, { "DOI": "10.3390/vaccines10101731", "article-title": "Nirmatrelvir/ritonavir and molnupiravir in the treatment of mild/moderate COVID-19: results of a real-life study", "author": "Gentile", "doi-asserted-by": "publisher", "first-page": "1731", "journal-title": "Vaccines", "key": "B7", "volume": "10", "year": "2022" }, { "DOI": "10.1056/NEJMoa2118542", "article-title": "Oral nirmatrelvir for high-risk, nonhospitalized adults with covid-19", "author": "Hammond", "doi-asserted-by": "publisher", "first-page": "1397", "journal-title": "N. Engl. J. Med.", "key": "B8", "volume": "386", "year": "2022" }, { "DOI": "10.3390/ijms23179866", "article-title": "The mechanism-based inactivation of CYP3A4 by ritonavir: what mechanism?", "author": "Loos", "doi-asserted-by": "publisher", "first-page": "9866", "journal-title": "Int. J. Mol. Sci.", "key": "B9", "volume": "23", "year": "2022" }, { "DOI": "10.1155/2022/7341493", "article-title": "Paxlovid: mechanism of action, synthesis, and in silico study", "author": "Marzi", "doi-asserted-by": "publisher", "first-page": "7341493", "journal-title": "BioMed Res. Int.", "key": "B10", "volume": "2022", "year": "2022" }, { "DOI": "10.1002/jmv.28660", "article-title": "Risk of hospitalization and sequelae in patients with COVID-19 treated with 3-day early remdesivir vs. controls in the vaccine and Omicron era: a real-life cohort study", "author": "Mazzitelli", "doi-asserted-by": "publisher", "first-page": "e28660", "journal-title": "J. 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(Weinheim, Baden-Wurttemberg, Ger.", "key": "B16", "volume": "7", "year": "2020" }, { "DOI": "10.1101/2023.01.23.23284899", "article-title": "Real-world effectiveness of Azvudine in hospitalized patients with COVID-19: a retrospective cohort study", "author": "Shen", "doi-asserted-by": "publisher", "key": "B17", "year": "2023" }, { "DOI": "10.1016/j.xcrm.2022.100549", "article-title": "Antiviral agents for the treatment of COVID-19: progress and challenges", "author": "Singh", "doi-asserted-by": "publisher", "first-page": "100549", "journal-title": "Cell. Rep. 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Dis.", "key": "B22", "volume": "22", "year": "" }, { "DOI": "10.1016/j.xinn.2022.100321", "article-title": "The first Chinese oral anti-COVID-19 drug Azvudine launched", "author": "Yu", "doi-asserted-by": "publisher", "first-page": "100321", "journal-title": "Innov. Camb. (Mass.))", "key": "B23", "volume": "3", "year": "2022" }, { "DOI": "10.1038/s41392-021-00835-6", "article-title": "Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients", "author": "Zhang", "doi-asserted-by": "publisher", "first-page": "414", "journal-title": "Signal Transduct. Target. Ther.", "key": "B24", "volume": "6", "year": "2021" }, { "DOI": "10.1016/j.jinf.2022.09.027", "article-title": "Efficacy and safety of Paxlovid for COVID-19:a meta-analysis", "author": "Zheng", "doi-asserted-by": "publisher", "first-page": "66", "journal-title": "J. Infect.", "key": "B25", "volume": "86", "year": "2023" }, { "DOI": "10.1101/2022.09.13.22279908", "article-title": "Real-world effectiveness of nirmatrelvir/ritonavir in preventing hospitalization among patients with COVID-19 at high risk for severe disease in the United States: a nationwide population-based cohort study", "author": "Zhou", "doi-asserted-by": "publisher", "key": "B26", "year": "2022" } ], "reference-count": 26, "references-count": 26, "relation": {}, "resource": { "primary": { "URL": "https://www.frontiersin.org/articles/10.3389/fphar.2023.1274294/full" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [ "Pharmacology (medical)", "Pharmacology" ], "subtitle": [], "title": "Head-to-head comparison of azvudine and nirmatrelvir/ritonavir for the hospitalized patients with COVID-19: a real-world retrospective cohort study with propensity score matching", "type": "journal-article", "update-policy": "http://dx.doi.org/10.3389/crossmark-policy", "volume": "14" }
Late treatment
is less effective
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