氫化可的松治療COVID-19重症患者不能改善第21天治療失敗率
作者：
小柯機器人發布時間：2020/9/8 21:36:27
法國布列塔尼醫院Pierre-François Dequin團隊探討了氫化可的松治療COVID-19重症患者對21天死亡或呼吸支持的影響。2020年9月2日，該研究發表在《美國醫學會雜誌》上。
COVID-19與嚴重肺損傷有關。皮質類固醇是一種可能的治療選擇。
為了探討氫化可的松對重症SARS-CoV-2感染和急性呼吸衰竭患者21天治療失敗的影響，研究組在法國進行了一項多中心、隨機、雙盲、序貫試驗，計劃每50例患者進行一次中期分析。2020年3月7日至6月1日，研究組招募了149名ICU收治的covid-19相關急性呼吸衰竭患者，將其隨機分組，其中76例接受低劑量氫化可的松治療，73例接受安慰劑治療。第21天治療失敗的主要結局定義為死亡或持續依賴機械通氣或高流量氧療。
149名患者的平均年齡為62.2歲，30.2%為女性，機械通氣佔81.2%。共有148名患者（99.3%）完成了試驗，69例治療失敗，其中氫化可的松組中有11人死亡，安慰劑組中有20人死亡。氫化可的松組中有32例（42.1%）患者出現21天治療失敗的主要結局，安慰劑組中有37例（50.7%），差異不顯著。兩組間預先指定的次要結局間均無統計學差異，且均未發生治療相關的嚴重不良事件。
研究結果表明，與安慰劑相比，低劑量氫化可的松治療重症covid-19並不能改善第21天治療失敗率。
附：英文原文
Title: Effect of Hydrocortisone on 21-Day Mortality or Respiratory Support Among Critically Ill Patients With COVID-19: A Randomized Clinical Trial
Author: Pierre-Franois Dequin, Nicholas Heming, Ferhat Meziani, Gatan Plantefève, Guillaume Voiriot, Julio Badié, Bruno Franois, Cécile Aubron, Jean-Damien Ricard, Stephan Ehrmann, Youenn Jouan, Antoine Guillon, Marie Leclerc, Carine Coffre, Hélène Bourgoin, Céline Lengellé, Caroline Caille-Fénérol, Elsa Tavernier, Sarah Zohar, Bruno Giraudeau, Djillali Annane, Amélie Le Gouge, for the CAPE COVID Trial Group and the CRICS-TriGGERSep Network
Issue&Volume: 2020-09-02
Abstract: Importance Coronavirus disease 2019 (COVID-19) is associated with severe lung damage. Corticosteroids are a possible therapeutic option.
Objective To determine the effect of hydrocortisone on treatment failure on day 21 in critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute respiratory failure.
Design, Setting, and Participants Multicenter randomized double-blind sequential trial conducted in France, with interim analyses planned every 50 patients. Patients admitted to the intensive care unit (ICU) for COVID-19–related acute respiratory failure were enrolled from March 7 to June 1, 2020, with last follow-up on June 29, 2020. The study intended to enroll 290 patients but was stopped early following the recommendation of the data and safety monitoring board.
Interventions Patients were randomized to receive low-dose hydrocortisone (n=76) or placebo (n=73).
Main Outcomes and Measures The primary outcome, treatment failure on day 21, was defined as death or persistent dependency on mechanical ventilation or high-flow oxygen therapy. Prespecified secondary outcomes included the need for tracheal intubation (among patients not intubated at baseline); cumulative incidences (until day 21) of prone position sessions, extracorporeal membrane oxygenation, and inhaled nitric oxide; Pao2:Fio2 ratio measured daily from day 1 to day 7, then on days 14 and 21; and the proportion of patients with secondary infections during their ICU stay.
Results The study was stopped after 149 patients (mean age, 62.2 years; 30.2% women; 81.2% mechanically ventilated) were enrolled. One hundred forty-eight patients (99.3%) completed the study, and there were 69 treatment failure events, including 11 deaths in the hydrocortisone group and 20 deaths in the placebo group. The primary outcome, treatment failure on day 21, occurred in 32 of 76 patients (42.1%) in the hydrocortisone group compared with 37 of 73 (50.7%) in the placebo group (difference of proportions, –8.6% [95.48% CI, –24.9% to 7.7%]; P=.29). Of the 4 prespecified secondary outcomes, none showed a significant difference. No serious adverse events were related to the study treatment.
Conclusions and Relevance In this study of critically ill patients with COVID-19 and acute respiratory failure, low-dose hydrocortisone, compared with placebo, did not significantly reduce treatment failure (defined as death or persistent respiratory support) at day 21. However, the study was stopped early and likely was underpowered to find a statistically and clinically important difference in the primary outcome.
DOI: 10.1001/jama.2020.16761
Source: https://jamanetwork.com/journals/jama/fullarticle/2770276