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[NEJM在线发表]:Beta-1b干扰素联合克立芝治疗中东呼吸综合征
2020年10月12日 时讯速递, 进展交流 暂无评论

ORIGINAL ARTICLE

Interferon Beta-1b and Lopinavir–Ritonavir for Middle East Respiratory Syndrome

Yaseen M. Arabi, Ayed Y. Asiri, Abdullah M. Assiri, et al

N Engl J Med October 7, 2020
DOI: 10.1056/NEJMoa2015294

Abstract 摘要

BACKGROUND 背景

Whether combined treatment with recombinant interferon beta-1b and lopinavir–ritonavir reduces mortality among patients hospitalized with Middle East respiratory syndrome (MERS) is unclear.

重组beta-1b干扰素与克立芝联合治疗能否降低中东呼吸综合征(MERS)住院患者病死率尚不清楚。

METHODS 方法

We conducted a randomized, adaptive, double-blind, placebo-controlled trial that enrolled patients at nine sites in Saudi Arabia. Hospitalized adults with laboratory-confirmed MERS were randomly assigned to receive recombinant interferon beta-1b plus lopinavir–ritonavir (intervention) or placebo for 14 days. The primary outcome was 90-day all-cause mortality, with a one-sided P-value threshold of 0.025. Prespecified subgroup analyses and safety analyses were conducted. Because of the pandemic of coronavirus disease 2019, the data and safety monitoring board requested an unplanned interim analysis and subsequently recommended the termination of enrollment and the reporting of the results.

我们进行了一项随机、适应性、双盲、安慰剂对照试验,在沙特阿拉伯的9个中心入选患者。我们将实验室确诊的MERS成年患者随机分组,分别接受重组beta-1b干扰素联合克立芝(干预组)或安慰剂,疗程14天。主要预后指标为90天全因病死率,单尾P值0.025。我们进行了预先确定的亚组分析及安全性分析。由于新冠病毒感染疫情爆发,数据及安全监督委员会要求进行计划外的中期分析,随后建议终止患者入选并报告结果。

RESULTS 结果

A total of 95 patients were enrolled; 43 patients were assigned to the intervention group and 52 to the placebo group. A total of 12 patients (28%) in the intervention group and 23 (44%) in the placebo group died by day 90. The analysis of the primary outcome, with accounting for the adaptive design, yielded a risk difference of −19 percentage points (upper boundary of the 97.5% confidence interval [CI], −3; one-sided P=0.024). In a prespecified subgroup analysis, treatment within 7 days after symptom onset led to lower 90-day mortality than use of placebo (relative risk, 0.19; 95% CI, 0.05 to 0.75), whereas later treatment did not. Serious adverse events occurred in 4 patients (9%) in the intervention group and in 10 (19%) in the placebo group.

共入选95名患者;43名患者分至干预组,52名患者分至安慰剂组。干预组12名(28%)患者及安慰剂组23名(44%)患者在90天内死亡。根据适应性设计进行校正后,主要预后指标风险差异为19个百分点(97.5%可信区间 [CI] 上限, −3; 单尾P=0.024)。在预先确定的亚组分析中,发病7天内进行治疗伴随90天病死率降低(相对危险度, 0.19; 95% CI, 0.05 to 0.75),而延迟治疗则不然。干预组4名(9%)患者与安慰剂组10名(19%)患者发生严重不良事件。

CONCLUSIONS 结论

A combination of recombinant interferon beta-1b and lopinavir–ritonavir led to lower mortality than placebo among patients who had been hospitalized with laboratory-confirmed MERS. The effect was greatest when treatment was started within 7 days after symptom onset.

对于实验室确诊的MERS住院患者,与安慰剂相比,联合重组beta-1b干扰素和克立芝能够降低病死率。发病7天内开始治疗时疗效更为明显。

(Funded by the King Abdullah International Medical Research Center; MIRACLE ClinicalTrials.gov number, NCT02845843. opens in new tab.)

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