背景:尽管有COVID-19疫苗接种,仍有必要研究治疗方法,以降低COVID-19潜在致命性并发症的风险或严重程度,如急性呼吸窘迫综合征(ARDS).这项研究评估了瞬时受体电位通道C6(TRPC6)抑制剂的疗效和安全性。BI764198,在降低因COVID-19住院并需要非侵入性治疗的患者ARDS的风险和/或严重程度方面,补充氧气支持(通过面罩或鼻叉进行氧气,通过非侵入性通气或高流量鼻腔吸氧)。
方法:多中心,双盲,随机II期试验比较每日一次口服BI764198(n=65)和安慰剂(n=64)28天(+2个月随访).
方法:第29天存活和无机械通气患者的比例。次要终点:存活和无氧出院的患者比例(第29天);任一院内死亡率的发生,重症监护病房入院或机械通气(第29天);首次缓解时间(临床改善/恢复);无呼吸机天数(第29天);和死亡率(第15、29、60和90天)。
结果:主要终点:BI764198(83.1%)与安慰剂(87.5%)无差异(估计风险差异-5.39%;95%CI-16.08至5.30;p=0.323)。对于次要端点,BI764198与安慰剂相比,首次缓解时间更长(比率0.67;95%CI0.46~0.99;p=0.045),住院时间更长(+3.41天;95%CI0.49~6.34;p=0.023);未观察到其他显著差异.试验组之间的治疗中不良事件相似,BI764198(n=7)与安慰剂(n=2)相比,报告了更多的致命事件。根据对缺乏疗效和致命事件失衡的中期观察,早期停止治疗(数据监测委员会建议)。
结论:在需要非侵入性治疗的COVID-19患者中,抑制TRPC6不能有效降低ARDS的风险和/或严重程度,补充氧气支持。
背景:NCT04604184。
Despite the availability of COVID-19 vaccinations, there remains a need to investigate treatments to reduce the risk or severity of potentially fatal complications of COVID-19, such as acute respiratory distress syndrome (ARDS). This
study evaluated the efficacy and safety of the transient receptor potential channel C6 (TRPC6) inhibitor, BI 764198, in reducing the risk and/or severity of ARDS in patients hospitalised for COVID-19 and requiring non-invasive, supplemental oxygen support (oxygen by mask or nasal prongs, oxygen by non-invasive ventilation or high-flow nasal oxygen).
Multicentre, double-blind, randomised phase II
trial comparing once-daily oral BI 764198 (n=65) with placebo (n=64) for 28 days (+2-month follow-up).
proportion of patients alive and free of mechanical ventilation at day 29. Secondary endpoints: proportion of patients alive and discharged without oxygen (day 29); occurrence of either in-hospital mortality, intensive care unit admission or mechanical ventilation (day 29); time to first response (clinical improvement/recovery); ventilator-free days (day 29); and mortality (days 15, 29, 60 and 90).
No difference was observed for the primary endpoint: BI 764198 (83.1%) versus placebo (87.5%) (estimated risk difference -5.39%; 95% CI -16.08 to 5.30; p=0.323). For secondary endpoints, a longer time to first response (rate ratio 0.67; 95% CI 0.46 to 0.99; p=0.045) and longer hospitalisation (+3.41 days; 95% CI 0.49 to 6.34; p=0.023) for BI 764198 versus placebo was observed; no other significant differences were observed. On-treatment adverse events were similar between
trial arms and more fatal events were reported for BI 764198 (n=7) versus placebo (n=2). Treatment was stopped early based on an interim observation of a lack of efficacy and an imbalance of fatal events (Data Monitoring Committee recommendation).
TRPC6 inhibition was not effective in reducing the risk and/or severity of ARDS in patients with COVID-19 requiring non-invasive, supplemental oxygen support.
NCT04604184.