Adjunctive corticosteroids in non-AIDS patients with severe Pneumocystis jirovecii pneumonia (PIC): a multicentre, double-blind, randomised controlled trial.

Adjunctive corticosteroids improve outcomes of P jirovecii pneumonia in HIV-positive patients.

辅助性皮质类固醇可改善HIV阳性患者肺孢子菌肺炎的预后。

The aim of this trial was to assess the effects of early adjunctive corticosteroid therapy for 21 days in HIV-negative patients with P jirovecii pneumonia responsible for acute hypoxaemia respiratory failure.

本试验旨在评估在HIV阴性患者中，对于由P jirovecii肺炎引起的急性低氧血症呼吸衰竭，早期辅助使用21天皮质类固醇治疗的效果。

Methods

This multicentre, double-blind, randomised controlled trialwas conducted at 27 hospitals in France.

这项多中心、双盲、随机对照试验在法国的27家医院进行。

We included patients with acute respiratory failure, aged 18 years or older with mild-to-severe hypoxaemia, microbiological documentation of P jirovecii pneumonia, and anti-Pneumocystis treatment duration of less than 7 days.

我们纳入了患有急性呼吸衰竭、年龄在18岁或以上、有轻度至重度低氧血症、P jirovecii肺炎的微生物学证明以及抗肺孢子菌治疗时间少于7天的患者。

Patients were randomly assigned (1:1) to the corticosteroid group (adjunctive corticosteroid therapy of methylprednisolone intravenously, 30 mg twice per day from days 1 to 5, 30 mg once per day from days 6 to 10, and 20 mg once per day until day 21) or placebo group (2 mL or 3 mL syringes of isotonic saline intravenously) using a web-based system.

患者通过基于网络的系统随机分配（1:1）到皮质类固醇组（辅助皮质类固醇治疗，甲基强的松龙静脉注射，第1至5天每天两次，每次30毫克，第6至10天每天一次，每次30毫克，直至第21天每天一次，每次20毫克）或安慰剂组（使用2毫升或3毫升注射器静脉注射等渗盐水）。

Permutation blocks of fixed size unknown to the local investigators were used.

使用了未知大小的固定排列块，当地研究者无法知道。

Stratification factors were centre, long-term corticosteroid treatment started more than 1 month before enrolling in the trial, underlying disease (malignancy vs other), and oxygen needs at randomisation (<6 vs ≥6 L per min).

分层因素包括研究中心、在纳入试验前1个月以上开始的长期皮质类固醇治疗、基础疾病（恶性肿瘤与其他）、以及随机化时的氧气需求（<6升/分钟与≥6升/分钟）。

The primary outcome was all-cause 28-day mortality defined as the proportion of patients who died within 28 days, analysed in the intention-to-treat(ITT) population.

主要结果是28天内全因死亡率，定义为28天内死亡的患者比例，在意向治疗（ITT）人群中进行分析。

This trial was registered on ClinicalTrials.gov, NCT02944045 (closed).

该试验已在ClinicalTrials.gov上注册，注册号为NCT02944045（已关闭）。

Results

From Feb 23, 2017, to Feb 23, 2024, 466 patients with acute respiratory failure were assessed for eligibility.

从2017年2月23日至2024年2月23日，共有466名急性呼吸衰竭患者被评估以确定其是否符合入选资格。

Of those, 240 were excluded and 226 patients were randomly assigned (114 assigned to the placebo group and 112 assigned to the corticosteroid group).

在这些患者中，有240名被排除在外，剩余的226名患者被随机分配（114名分配至安慰剂组，112名分配至皮质类固醇组）。

The ITT population included 111 patients in the placebo group and 107 in the corticosteroid group.

意向性治疗(ITT)人群包括111名安慰剂组患者和107名皮质类固醇组患者。

Median age was 67 years (IQR 59-73). 126 (58%) patients were male and 92 (42%) were female.

中位年龄为67岁（四分位数间距59-73）。共有126名（58%）患者为男性，92名（42%）为女性。

Nearly all patients (208 [95%]) were in the ICU or intermediate care at randomisation.

几乎所有患者（208 [95%]）在随机分组时都在重症监护室或中级护理中。

The median time from P jirovecii pneumonia diagnosis to corticosteroid therapy initiation was 3 days (IQR 2-5).

从P jirovecii肺炎诊断到皮质类固醇治疗开始的中位时间是3天（四分位数间距2-5天）。

Patients received trial treatment for 13 days (range 7-20).

患者接受了试验治疗，平均持续13天（范围7-20天）。

All-cause 28-day mortality occurred in 36 (32·4%) patients in the placebo group versus 23 (21·5%) in the corticosteroid group (mean difference 10·9% [95% CI -0·9 to 22·5]; p=0·069).

在安慰剂组中，28天内全因死亡发生在36名（32.4%）患者中，而在皮质类固醇组中为23名（21.5%）患者（平均差异10.9% [95% 置信区间 -0.9 到 22.5]；p=0.069）。

There were no significant differences in safety outcomes between groups, especially for all secondary infections (38 [34·2%; 95% CI 25·4 to 43·1] patients in the placebo group vs 25 [23·4%; 15·3 to 31·4] in the corticosteroid group) or insulin needs (25 [22·5%; 15·1 to 31·4] vs 33 [30·8%; 22·3 to 40·5]).

两组在安全性结果上没有显著差异，特别是对于所有次级感染（安慰剂组38例[34.2%；95%置信区间25.4至43.1]，皮质类固醇组25例[23.4%；15.3至31.4]）或胰岛素需求（安慰剂组25例[22.5%；15.1至31.4]，皮质类固醇组33例[30.8%；22.3至40.5]）。

interpretation

In immunocompromised HIV-negative patients with P jirovecii pneumonia, adjunctive corticosteroid treatment did not significantly decrease 28-day mortality.

对于免疫功能受损的HIV阴性患者，伴有P jirovecii肺炎的辅助皮质类固醇治疗并未显著降低28天死亡率。

funding

French Ministry of Health.

法国卫生部