Alma Mater Studiorum-Università di Bologna, Dipartimento di Scienze Mediche e Chirurgiche, Anesthesia and Intensive Care Medicine, Policlinico di Sant'Orsola, Bologna, Italy.
Division of Intensive Care, Department of Anesthesiology, Intensive Care, and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
JAMA. 2020 Feb 25;323(8):725-733. doi: 10.1001/jama.2019.22525.
Acute respiratory distress syndrome (ARDS) is associated with high mortality. Interferon (IFN) β-1a may prevent the underlying event of vascular leakage.
To determine the efficacy and adverse events of IFN-β-1a in patients with moderate to severe ARDS.
DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized, double-blind, parallel-group trial conducted at 74 intensive care units in 8 European countries (December 2015-December 2017) that included 301 adults with moderate to severe ARDS according to the Berlin definition. The radiological and partial pressure of oxygen, arterial (Pao2)/fraction of inspired oxygen (Fio2) criteria for ARDS had to be met within a 24-hour period, and the administration of the first dose of the study drug had to occur within 48 hours of the diagnosis of ARDS. The last patient visit was on March 6, 2018.
Patients were randomized to receive an intravenous injection of 10 μg of IFN-β-1a (144 patients) or placebo (152 patients) once daily for 6 days.
The primary outcome was a score combining death and number of ventilator-free days at day 28 (score ranged from -1 for death to 27 if the patient was off ventilator on the first day). There were 16 secondary outcomes, including 28-day mortality, which were tested hierarchically to control type I error.
Among 301 patients who were randomized (mean age, 58 years; 103 women [34.2%]), 296 (98.3%) completed the trial and were included in the primary analysis. At 28 days, the median composite score of death and number of ventilator-free days at day 28 was 10 days (interquartile range, -1 to 20) in the IFN-β-1a group and 8.5 days (interquartile range, 0 to 20) in the placebo group (P = .82). There was no significant difference in 28-day mortality between the IFN-β-1a vs placebo groups (26.4% vs 23.0%; difference, 3.4% [95% CI, -8.1% to 14.8%]; P = .53). Seventy-four patients (25.0%) experienced adverse events considered to be related to treatment during the study (41 patients [28.5%] in the IFN-β-1a group and 33 [21.7%] in the placebo group).
Among adults with moderate or severe ARDS, intravenous IFN-β-1a administered for 6 days, compared with placebo, resulted in no significant difference in a composite score that included death and number of ventilator-free days over 28 days. These results do not support the use of IFN-β-1a in the management of ARDS.
ClinicalTrials.gov Identifier: NCT02622724.
急性呼吸窘迫综合征（ARDS）与高死亡率相关。干扰素（IFN）β-1a 可能预防血管渗漏的根本事件。
确定 IFN-β-1a 在中重度 ARDS 患者中的疗效和不良事件。
设计、地点和参与者：在 8 个欧洲国家的 74 个重症监护病房进行的多中心、随机、双盲、平行组试验（2015 年 12 月至 2017 年 12 月），包括 301 名根据柏林定义的中重度 ARDS 成人。放射学和部分氧气压力，动脉（Pao2）/吸入氧气分数（Fio2）的 ARDS 标准必须在 24 小时内得到满足，并且研究药物的第一次剂量必须在 ARDS 诊断后 48 小时内给予。最后一次患者就诊是在 2018 年 3 月 6 日。
患者被随机分配接受 10 μg IFN-β-1a（144 名患者）或安慰剂（152 名患者）静脉注射，每天一次，持续 6 天。
主要结局是死亡和第 28 天无呼吸机天数的评分相结合（评分范围从死亡的-1 到第 1 天无呼吸机的 27）。有 16 个次要结局，包括 28 天死亡率，这些结局按层次进行测试以控制 I 型错误。
在 301 名随机患者中（平均年龄 58 岁；103 名女性[34.2%]），296 名（98.3%）完成了试验并纳入了主要分析。在 28 天时，IFN-β-1a 组的 28 天死亡和无呼吸机天数的复合评分中位数为 10 天（四分位距，-1 至 20），安慰剂组为 8.5 天（四分位距，0 至 20）（P = .82）。IFN-β-1a 组与安慰剂组 28 天死亡率无显著差异（26.4% vs 23.0%；差异，3.4%[95%CI，-8.1%至 14.8%]；P = .53）。在研究期间，74 名患者（25.0%）经历了被认为与治疗相关的不良事件（IFN-β-1a 组 41 名[28.5%]，安慰剂组 33 名[21.7%]）。
在中重度 ARDS 成人中，与安慰剂相比，静脉内 IFN-β-1a 给药 6 天，在 28 天内死亡和无呼吸机天数的复合评分方面没有显著差异。这些结果不支持使用 IFN-β-1a 治疗 ARDS。
ClinicalTrials.gov 标识符：NCT02622724。
