PDF(Pubmed)
Abstract：
Background: To date, no oral antiviral drug has proven to be beneficial in hospitalized patients with COVID-19. Methods: 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. Results: 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, p = 0.008) and demonstrated less progression to MV or death [6/101 (5.9%) vs. 15/100 (15%), p = 0.036] and a shorter LOS (12 vs. 14 days, p = 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%), p = 0.089] was observed. Conclusion: 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. Systematic Review Registration: [https://clinicaltrials.gov/ct2/show/NCT04351724, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001302-30/AT], identifier [NCT04351724, EUDRACT-NR: 2020-001302-30].
摘要：
背景：迄今为止，没有口服抗病毒药物被证明对COVID-19住院患者有益。方法：在这个随机的，控制,开放标签，平台试用,我们将≥18岁的COVID-19肺炎患者随机分组,分别接受甲磺酸卡莫司他(CM)(考虑标准治疗)或洛匹那韦/利托那韦(LPV/RTV)治疗.主要终点是WHO7类量表中至少1点的持续临床改善时间（≥48小时）。次要终点包括住院时间（LOS），需要机械通气（MV）或死亡，29天死亡率结果：在2020年4月20日至2021年5月14日期间，201例患者被纳入研究（101CM和100LPV/RTV）。平均年龄58.7岁,67%为男性。从症状发作到随机化的中位时间为7天(IQR5-9)。CM组患者的持续临床改善时间明显缩短（HR=0.67，95％-CI0.49-0.90；9vs.11天,p=0.008），并显示出更少的MV或死亡进展[6/101（5.9％）与15/100（15%），p=0.036]和较短的LOS(12vs.14天,p=0.023)。CM组29天死亡率低于LPV/RTV组[2/101(2%)vs.7/100（7%），观察到p=0.089]。结论：在COVID-19住院患者中，使用CM与缩短临床改善时间相关，减少对MV或死亡的需求，和更短的LOS比使用LPV/RTV。此外，需要研究证实CM在更大的安慰剂对照试验中的疗效.系统审查注册：[https://clinicaltrials.gov/ct2/show/NCT04351724，https://www。临床试验登记。欧盟/ctr-search/trial/2020-001302-30/AT]，标识符[NCT04351724,EUDRACT-NR:2020-001302-30]。
