美国匹兹堡大学Derek C. Angus团队分析了氢化可的松治疗COVID-19重症患者对死亡率和器官支持的影响。2020年9月2日，该研究发表在《美国医学会杂志》上。

使用皮质类固醇治疗COVID-19的疗效尚不明确。

为了探讨氢化可的松能否改善COVID-19重症患者的预后，2020年3月9日至6月17日，研究组在8个国家/地区的121个站点招募了614名疑似或确诊COVID-19的成年患者，均接受重症监护病房（ICU）的呼吸机或心血管器官支持。

403例被随机分配到皮质类固醇的开放标签干预试验，其中143例接受固定7天静脉注射氢化可的松，152例仅当临床上有明显休克时则进行氢化可的松治疗，108例患者未接受氢化可的松治疗。主要终点为治疗21天内无器官支持的天数，包括存活和无ICU基础呼吸或心血管支持的天数。死亡患者被分配到-1天。

排除19名撤销知情同意的参与者后，共有384名患者参加试验，平均年龄为60岁，29%为女性，其中固定剂量组137名，休克依赖组146名，无氢化可的松组101名；共有379人（99%）完成研究，纳入最终分析。

三组患者的平均年龄在59.5-60.4岁之间；男性居多，占70.6%-71.5%；平均体重指数为29.7-30.9；接受机械通气的患者占50.0%-63.5%。对于固定剂量组、休克依赖组和无氢化可的松组，无器官支持的中位天数均为0天，死亡率分别为30％、26％和33％，幸存者的无器官支持的中位天数分别为11.5、9.5和6天。

与无氢化可的松组相比，固定剂量组的中位校正比值比和贝叶斯优势概率分别为1.43和93%，休克依赖组分别为1.22和80%。固定剂量组、休克依赖组和无氢化可的松组分别发生4（3%）、5（3%）和1（1%）例严重不良事件。

总之，对于COVID-19重症患者，采用氢化可的松连续7天固定剂量或休克依赖剂量治疗，与未接受氢化可的松治疗相比，有较大几率可改善21天内无器官支持的天数。

附：英文原文

Title: Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial

Author: The Writing Committee for the REMAP-CAP Investigators, Derek C. Angus, Lennie Derde, Farah Al-Beidh, Djillali Annane, Yaseen Arabi, Abigail Beane, Wilma van Bentum-Puijk, Lindsay Berry, Zahra Bhimani, Marc Bonten, Charlotte Bradbury, Frank Brunkhorst, Meredith Buxton, Adrian Buzgau, Allen C. Cheng, Menno de Jong, Michelle Detry, Lise Estcourt, Mark Fitzgerald, Herman Goossens, Cameron Green, Rashan Haniffa, Alisa M. Higgins, Christopher Horvat, Sebastiaan J. Hullegie, Peter Kruger, Francois Lamontagne, Patrick R. Lawler, Kelsey Linstrum, Edward Litton, Elizabeth Lorenzi, John Marshall, Daniel McAuley, Anna McGlothin, Shay McGuinness, Bryan McVerry, Stephanie Montgomery, Paul Mouncey, Srinivas Murthy, Alistair Nichol, Rachael Parke, Jane Parker, Kathryn Rowan, Ashish Sanil, Marlene Santos, Christina Saunders, Christopher Seymour, Anne Turner, Frank van de Veerdonk, Balasubramanian Venkatesh, Ryan Zarychanski, Scott Berry, Roger J. Lewis, Colin McArthur, Steven A. Webb, Anthony C. Gordon

Issue&Volume: 2020-09-02

Abstract:

Importance  Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited.

Objective  To determine whether hydrocortisone improves outcome for patients with severe COVID-19.

Design, Setting, and Participants  An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020.

Interventions  The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n=143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n=152), or no hydrocortisone (n=108).

Main Outcomes and Measures  The primary end point was organ support–free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned –1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%).

Results  After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n=137), shock-dependent (n=146), and no (n=101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support–free days were 0 (IQR, –1 to 15), 0 (IQR, –1 to 13), and 0 (–1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support–free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively.

Conclusions and Relevance  Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support–free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions.

DOI: 10.1001/jama.2020.17022

Source: https://jamanetwork.com/journals/jama/fullarticle/2770278