两种不同地塞米松给药方案对中度至重度急性呼吸窘迫综合征的 COVID-19 患者无呼吸机天数和长期死亡率的影响：REMED 随机临床试验

Effects of two different dexamethasone dosing regimens on ventilator-free days and long-term mortality in COVID-19 patients with moderate-to-severe ARDS: the REMED randomized clinical trial.

作者信息

Maláska Jan, Stašek Jan, Máca Jan, Kutěj Martin, Duška František, Kafka Petr, Klementová Olga, Doubravská Lenka, Hruda Jan, Fencl Marek, Gabrhelík Tomáš, Číž Libor, Zatloukal Jan, Pouska Jiří, Novotný Pavel, Balík Martin, Demlová Regina, Kubátová Jana, Vinklerová Jana, Grodová Karolína, Štěpánová Radka, Svobodník Adam, Kratochvíl Milan, Klučka Jozef, Štourač Petr, Singer Mervyn

机构信息

Department of Paediatric Anaesthesiology and Intensive Care Medicine, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic.

Department of Simulation Medicine, Faculty of Medicine, Masaryk University, Brno, Czech Republic.

出版信息

Eur J Med Res. 2024 Dec 23;29(1):616. doi: 10.1186/s40001-024-02215-6.

DOI:10.1186/s40001-024-02215-6

PMID:39710693

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11664838/

Abstract

BACKGROUND

Dexamethasone 6 mg in patients with severe COVID-19 has been shown to decrease mortality and morbidity. The effects of higher doses of corticosteroid, that would further increase anti-inflammatory effects, are uncertain. The objective of our study was to assess the effect of 20 mg dexamethasone vs. 6 mg dexamethasone intravenously in patients with moderate-to-severe acute respiratory distress syndrome (ARDS) and COVID-19.

METHODS

In a multicenter, open-label, randomized trial conducted in nine hospitals in the Czech Republic, we randomized adult patients with ARDS and COVID-19 requiring high-flow oxygen, noninvasive or invasive mechanical ventilation to receive either intravenous high-dose dexamethasone (20 mg/day on days 1-5, 10 mg/day on days 6-10) or standard-dose dexamethasone (6 mg/d, days 1-10). The primary outcome was 28-day ventilator-free days. The five secondary outcomes were 60-day mortality, C-reactive protein dynamics, 14-day WHO (World Health Organization) Clinical Progression Scale score, adverse events and 90-day Barthel index. The long-term outcomes were 180- and 360-day mortality and the Barthel index. The planned sample size was 300, with interim analysis after enrollment of 150 patients.

RESULTS

The trial was stopped due to a lack of recruitment, and the follow-up was completed in February 2023. Among 234 randomized patients of 300 planned patients, the primary outcome was available for 224 patients (110 high-dose and 114 standard-dose dexamethasone; median [interquartile range (IQR)] age, 59.0 [48.5-66.0] years; 130 [58.0%] were receiving noninvasive or invasive mechanical ventilation at baseline). The mean number of 28-day ventilator-free days was 8.9 (± 11.5) days for high-dose dexamethasone and 8.0 (± 10.7) days for standard-dose dexamethasone, with an absolute difference of + 0.81 days (95% CI - 2.12-3.73 days). None of the prespecified secondary outcomes, including adverse events, differed between the groups.

CONCLUSIONS

Despite not reaching its prespecified enrollment, there was no signal to either benefit or harm high-dose dexamethasone over standard-dose dexamethasone in patients with COVID-19 and moderate-to-severe ARDS. Trial registration Trial registration: ClinicalTrials.gov Identifier: NCT04663555. Registered 10 December 2020, https://clinicaltrials.gov/study/NCT04663555?term=NCT04663555&rank=1 and EudraCT: 2020-005887-70.

摘要

背景

已证明，对于重症新型冠状病毒肺炎（COVID-19）患者，静脉注射6毫克地塞米松可降低死亡率和发病率。更高剂量的皮质类固醇激素可进一步增强抗炎作用，但其效果尚不确定。我们研究的目的是评估静脉注射20毫克地塞米松与6毫克地塞米松对中重度急性呼吸窘迫综合征（ARDS）合并COVID-19患者的影响。

方法

在捷克共和国九家医院进行的一项多中心、开放标签、随机试验中，我们将需要高流量吸氧、无创或有创机械通气的ARDS合并COVID-19成年患者随机分为两组，分别接受静脉注射高剂量地塞米松（第1 - 5天20毫克/天，第6 - 10天10毫克/天）或标准剂量地塞米松（第1 - 10天6毫克/天）。主要结局是28天无呼吸机天数。五个次要结局是60天死亡率、C反应蛋白动态变化、14天世界卫生组织（WHO）临床进展量表评分、不良事件和90天巴氏指数。长期结局是180天和360天死亡率以及巴氏指数。计划样本量为300例，在入组150例患者后进行中期分析。

结果

由于招募不足，该试验提前终止，随访于2023年2月完成。在计划纳入的300例患者中的234例随机分组患者中，224例患者有主要结局数据（110例接受高剂量地塞米松，114例接受标准剂量地塞米松；年龄中位数[四分位间距（IQR）]为59.0[48.5 - 66.0]岁；130例[58.0%]在基线时接受无创或有创机械通气）。高剂量地塞米松组28天无呼吸机天数的均值为8.9（±11.5）天，标准剂量地塞米松组为8.0（±10.7）天，绝对差异为 + 0.81天（95%CI - 2.12 - 3.73天）。两组之间，包括不良事件在内，所有预先设定的次要结局均无差异。

结论

尽管未达到预定的入组人数，但对于COVID-19合并中重度ARDS患者，高剂量地塞米松与标准剂量地塞米松相比，未显示出有益或有害的迹象。试验注册试验注册：ClinicalTrials.gov标识符：NCT04663555。于2020年12月10日注册，https://clinicaltrials.gov/study/NCT04663555?term=NCT04663555&rank=1 以及欧盟临床试验数据库（EudraCT）：2020 - 005887 - 70。