Inserm 1219 Bordeaux Population Health, Université de Bordeaux, Bordeaux, France; Department of Infectious Diseases and Tropical Medicine, CHU Bordeaux, Bordeaux, France; IRD 271, Bordeaux, France.
Inserm 1219 Bordeaux Population Health, Université de Bordeaux, Bordeaux, France; CIC 1401, EUCLID/F-CRIN Clinical Trials Platform, Bordeaux, France; Inria SISTM, Bordeaux, France; Department of Public Health, CHU Bordeaux, Bordeaux, France.
Clin Microbiol Infect. 2022 Jul;28(7):1010-1016. doi: 10.1016/j.cmi.2022.02.031. Epub 2022 Mar 15.
To assess the efficacy of inhaled ciclesonide in reducing the risk of adverse outcomes in COVID-19 outpatients at risk of developing severe illness.
COVERAGE is an open-label, randomized controlled trial. Outpatients with documented COVID-19, risk factors for aggravation, symptoms for ≤7 days, and absence of criteria for hospitalization are randomly allocated to either a control arm or one of several experimental arms, including inhaled ciclesonide. The primary efficacy endpoint is COVID-19 worsening (hospitalization, oxygen therapy at home, or death) by Day 14. Other endpoints are adverse events, maximal follow-up score on the WHO Ordinal Scale for Clinical Improvement, sustained alleviation of symptoms, cure, and RT-PCR and blood parameter evolution at Day 7. The trial's Safety Monitoring Board reviewed the first interim analysis of the ciclesonide arm and recommended halting it for futility. The results of this analysis are reported here.
The analysis involved 217 participants (control 107, ciclesonide 110), including 111 women and 106 men. Their median age was 63 years (interquartile range 59-68), and 157 of 217 (72.4%) had at least one comorbidity. The median time since first symptom was 4 days (interquartile range 3-5). During the 28-day follow-up, 2 participants died (control 2/107 [1.9%], ciclesonide 0), 4 received oxygen therapy at home and were not hospitalized (control 2/107 [1.9%], ciclesonide 2/110 [1.8%]), and 24 were hospitalized (control 10/107 [9.3%], ciclesonide 14/110 [12.7%]). In intent-to-treat analysis of observed data, 26 participants reached the composite primary endpoint by Day 14, including 12 of 106 (11.3%, 95% CI: 6.0%-18.9%) in the control arm and 14 of 106 (13.2%; 95% CI: 7.4-21.2%) in the ciclesonide arm. Secondary outcomes were similar for both arms.
Our findings are consistent with the European Medicines Agency's COVID-19 task force statement that there is currently insufficient evidence that inhaled corticosteroids are beneficial for patients with COVID-19.
评估吸入性环索奈德降低 COVID-19 门诊患者发生重症风险的疗效。
COVERAGE 是一项开放性标签、随机对照试验。患有确诊 COVID-19、病情加重风险因素、症状持续时间≤7 天且无住院标准的门诊患者，随机分配到对照组或实验组，实验组包括吸入性环索奈德。主要疗效终点为第 14 天 COVID-19 恶化（住院、家庭氧疗或死亡）。其他终点为不良事件、WHO 临床改善等级量表的最大随访评分、症状持续缓解、治愈以及第 7 天的 RT-PCR 和血液参数变化。试验安全监测委员会审查了环索奈德组的第一次中期分析结果，并建议因无效而停止该组。本分析报告了该结果。
分析纳入了 217 名参与者（对照组 107 名，环索奈德组 110 名），包括 111 名女性和 106 名男性。他们的中位年龄为 63 岁（四分位距 59-68），217 名患者中有 157 名至少有 1 种合并症。从首次症状出现到中位时间为 4 天（四分位距 3-5）。在 28 天的随访期间，2 名患者死亡（对照组 2/107[1.9%]，环索奈德组 0），4 名患者接受家庭氧疗但未住院（对照组 2/107[1.9%]，环索奈德组 2/110[1.8%]），24 名患者住院（对照组 10/107[9.3%]，环索奈德组 14/110[12.7%]）。在观察数据的意向治疗分析中，第 14 天，26 名参与者达到了复合主要终点，包括对照组 106 名患者中的 12 名（11.3%，95%CI：6.0%-18.9%）和环索奈德组 106 名患者中的 14 名（13.2%，95%CI：7.4-21.2%）。次要结局在两组中相似。
我们的发现与欧洲药品管理局 COVID-19 工作组的声明一致，即目前没有足够的证据表明吸入性皮质类固醇对 COVID-19 患者有益。
