Karolyi M, Pawelka E, Omid S, Koenig F, Kauer V, Rumpf B, Hoepler W, Kuran A, Laferl H, Seitz T, Traugott M, Rathkolb V, Mueller M, Abrahamowicz A, Schoergenhofer C, Hecking M, Assinger A, Wenisch C, Zeitlinger M, Jilma B, Zoufaly A
Department for Infectious Diseases and Tropical Medicine, Klinik Favoriten, Vienna, Austria.
Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria.
Front Pharmacol. 2022 Jul 22;13:870493. doi: 10.3389/fphar.2022.870493. eCollection 2022.
To date, no oral antiviral drug has proven to be beneficial in hospitalized patients with COVID-19. In this randomized, controlled, open-label, platform trial, we randomly assigned patients ≥18 years hospitalized with COVID-19 pneumonia to receive either camostat mesylate (CM) (considered standard-of-care) or lopinavir/ritonavir (LPV/RTV). The primary endpoint was time to sustained clinical improvement (≥48 h) of at least one point on the 7-category WHO scale. Secondary endpoints included length of stay (LOS), need for mechanical ventilation (MV) or death, and 29-day mortality. 201 patients were included in the study (101 CM and 100 LPV/RTV) between 20 April 2020 and 14 May 2021. Mean age was 58.7 years, and 67% were male. The median time from symptom onset to randomization was 7 days (IQR 5-9). Patients in the CM group had a significantly shorter time to sustained clinical improvement (HR = 0.67, 95%-CI 0.49-0.90; 9 vs. 11 days, = 0.008) and demonstrated less progression to MV or death [6/101 (5.9%) vs. 15/100 (15%), = 0.036] and a shorter LOS (12 vs. 14 days, = 0.023). A statistically nonsignificant trend toward a lower 29-day mortality in the CM group than the LPV/RTV group [2/101 (2%) vs. 7/100 (7%), = 0.089] was observed. In patients hospitalized for COVID-19, the use of CM was associated with shorter time to clinical improvement, reduced need for MV or death, and shorter LOS than the use of LPV/RTV. Furthermore, research is needed to confirm the efficacy of CM in larger placebo-controlled trials. : [https://clinicaltrials.gov/ct2/show/NCT04351724, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001302-30/AT], identifier [NCT04351724, EUDRACT-NR: 2020-001302-30].
迄今为止，尚无口服抗病毒药物被证明对新冠肺炎住院患者有益。在这项随机、对照、开放标签的平台试验中，我们将年龄≥18岁的新冠肺炎肺炎住院患者随机分配，使其接受甲磺酸卡莫司他（CM）（视为标准治疗）或洛匹那韦/利托那韦（LPV/RTV）治疗。主要终点是在世界卫生组织7级量表上至少有1分实现持续临床改善（≥48小时）的时间。次要终点包括住院时间（LOS）、是否需要机械通气（MV）或死亡以及29天死亡率。2020年4月20日至2021年5月14日期间，201名患者纳入研究（101名接受CM治疗，100名接受LPV/RTV治疗）。平均年龄为58.7岁，67%为男性。从症状出现到随机分组的中位时间为7天（四分位间距5 - 9天）。CM组患者实现持续临床改善的时间显著更短（HR = 0.67，95%置信区间0.49 - 0.90；分别为9天和11天，P = 0.008），进展为MV或死亡的情况更少[6/101（5.9%）对15/100（15%），P = 0.036]，住院时间更短（12天对14天，P = 0.023）。观察到CM组29天死亡率低于LPV/RTV组，但差异无统计学意义[2/101（2%）对7/100（7%），P = 0.089]。在新冠肺炎住院患者中，与使用LPV/RTV相比，使用CM可使临床改善时间更短，MV或死亡需求减少，住院时间缩短。此外，需要开展研究以在更大规模的安慰剂对照试验中确认CM的疗效。：[https://clinicaltrials.gov/ct2/show/NCT04351724, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001302-30/AT]，标识符[NCT04351724, EUDRACT-NR: 2020-001302-30]
