美国范德比尔特大学医学中心Wesley H. Self团队研究了羟氯喹治疗COVID-19住院患者的疗效。2020年11月9日，该研究发表在《美国医学会杂志》上。

目前关于羟氯喹治疗COVID-19的数据仍不足。为了确定羟氯喹治疗COVID-19住院成人是否有效，研究组在美国34家医院进行了一项多中心、双盲、安慰剂对照的随机试验。2020年4月2日至7月17日，研究组共招募了479名SARS-CoV-2感染且合并呼吸道症状的住院患者。

将这些患者随机分配，其中242名接受羟氯喹治疗，237名接受安慰剂治疗。主要结局为随机分组后14天的临床状况，按1级（死亡）至7级（出院并能够进行正常活动）的7级序数进行评估。12个次要结局中包括28天死亡率。

479名患者的中位年龄为57岁，女性占44.3％。西班牙裔/拉丁裔占37.2％，黑人占23.4％。重症监护病房患者占20.1％，接受无正压补充氧气的患者占46.8％，接受无创通气或鼻高流量供氧的患者占11.5％，接受有创机械通气或体外膜氧合的患者占6.7％。共有433名（90.4％）患者在14天时完成了主要结局评估，其余患者则临床状况不明。

患者随机分组之前症状的中位持续时间为5天。羟氯喹组和安慰剂组患者的14天临床状况序级评估没有显著差异。两组之间的12个次要结局均无显著差异。随机分组后28天，羟氯喹组241名患者中有25名（10.4％）死亡，安慰剂组236名患者中有25名（10.6％）。

研究结果表明，对于因COVID-19引发呼吸道疾病而住院的成年人中，与安慰剂相比，采用羟氯喹治疗并未显著改善第14天的临床状况。

附：英文原文

Title: Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial

Author: Wesley H. Self, Matthew W. Semler, Lindsay M. Leither, Jonathan D. Casey, Derek C. Angus, Roy G. Brower, Steven Y. Chang, Sean P. Collins, John C. Eppensteiner, Michael R. Filbin, D. Clark Files, Kevin W. Gibbs, Adit A. Ginde, Michelle N. Gong, Frank E. Harrell, Douglas L. Hayden, Catherine L. Hough, Nicholas J. Johnson, Akram Khan, Christopher J. Lindsell, Michael A. Matthay, Marc Moss, Pauline K. Park, Todd W. Rice, Bryce R. H. Robinson, David A. Schoenfeld, Nathan I. Shapiro, Jay S. Steingrub, Christine A. Ulysse, Alexandra Weissman, Donald M. Yealy, B. Taylor Thompson, Samuel M. Brown, National Heart, Lung, and Blood Institute PETAL Clinical Trials Network

Issue&Volume: 2020-11-09

Abstract:

Importance  Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed.

Objective  To determine whether hydroxychloroquine is an efficacious treatment for adults hospitalized with COVID-19.

Design, Setting, and Participants  This was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled between April 2 and June 19, 2020, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients, with interim analyses planned after every 102 patients were enrolled. The trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients.

Interventions  Patients were randomly assigned to hydroxychloroquine (400 mg twice daily for 2 doses, then 200 mg twice daily for 8 doses) (n=242) or placebo (n=237).

Main Outcomes and Measures  The primary outcome was clinical status 14 days after randomization as assessed with a 7-category ordinal scale ranging from 1 (death) to 7 (discharged from the hospital and able to perform normal activities). The primary outcome was analyzed with a multivariable proportional odds model, with an adjusted odds ratio (aOR) greater than 1.0 indicating more favorable outcomes with hydroxychloroquine than placebo. The trial included 12 secondary outcomes, including 28-day mortality.

Results  Among 479 patients who were randomized (median age, 57 years; 44.3% female; 37.2% Hispanic/Latinx; 23.4% Black; 20.1% in the intensive care unit; 46.8% receiving supplemental oxygen without positive pressure; 11.5% receiving noninvasive ventilation or nasal high-flow oxygen; and 6.7% receiving invasive mechanical ventilation or extracorporeal membrane oxygenation), 433 (90.4%) completed the primary outcome assessment at 14 days and the remainder had clinical status imputed. The median duration of symptoms prior to randomization was 5 days (interquartile range [IQR], 3 to 7 days). Clinical status on the ordinal outcome scale at 14 days did not significantly differ between the hydroxychloroquine and placebo groups (median [IQR] score, 6 [4-7] vs 6 [4-7]; aOR, 1.02 [95% CI, 0.73 to 1.42]). None of the 12 secondary outcomes were significantly different between groups. At 28 days after randomization, 25 of 241 patients (10.4%) in the hydroxychloroquine group and 25 of 236 (10.6%) in the placebo group had died (absolute difference, 0.2% [95% CI, 5.7% to 5.3%]; aOR, 1.07 [95% CI, 0.54 to 2.09]).

Conclusions and Relevance  Among adults hospitalized with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14. These findings do not support the use of hydroxychloroquine for treatment of COVID-19 among hospitalized adults.

DOI: 10.1001/jama.2020.22240

Source: https://jamanetwork.com/journals/jama/fullarticle/2772922