A European multicentre, randomised controlled trial of pirfenidone in bronchiolitis obliterans syndrome after bilateral lung transplantation.

Bronchiolitis obliterans syndrome (BOS), characterised by progressive decline in forced expiratory volume in 1 s (FEV1) due to fibrotic scarring of the small airways, accounts for most CLAD cases.

闭塞性细支气管炎综合征（BOS），其特征是由于小气道纤维化瘢痕而导致的一秒钟用力呼气量（FEV1）逐渐下降，占大多数CLAD病例。

Pirfenidone, an antifibrotic agent used for idiopathic pulmonary fibrosis, was assessed for treating progressive BOS.

Pirfenidone，一种用于特发性肺纤维化的抗纤维化药物，被评估用于治疗进行性BOS。

Methods

An investigator-initiated, international, multicentre, randomised, double-blind, placebo-controlledphase II trial was conducted in nine European lung transplant centres.

在九个欧洲肺移植中心进行了一项由研究者发起的国际多中心、随机、双盲、安慰剂对照的II期临床试验。

Adults with bilateral lung transplants and progressive BOS were randomised (1:1) to receive pirfenidone 2403 mg·day-1 or placebo with standard care for 26 weeks.

成年双侧肺移植患者和进展性支气管肺泡灌洗液（BOS）被随机分配（1:1）接受每日2403毫克的吡非尼酮或安慰剂，配合标准治疗，为期26周。

The primary end-point was change in FEV1 from baseline to week 26, with imputation for missing values.

主要终点是基线至第26周的第1秒用力呼气量（FEV1）变化，对于缺失值进行了估算。

Results

From 1 May 2015 to 1 December 2019, 477 patients were screened, and 90 were randomised to pirfenidone (n=48) or placebo (n=42).

从2015年5月1日至2019年12月1日，共筛查了477名患者，其中90名被随机分配至吡非尼酮组(n=48)或安慰剂组(n=42)。

Both groups showed continued decline in FEV1 from baseline to week 26, with no significant difference in intention to treat (ITT), ITT with imputation, or per-protocol analyses.

两组患者从基线到第26周的FEV1持续下降，无论是在意向治疗(ITT)、带有估算值的ITT还是按方案分析中，均未显示出显著差异。

Secondary end-points (graft loss, death, re-transplantation) were similar between groups.

次要终点事件（移植物丢失、死亡、再次移植）在各组之间相似。

Treatment-related serious adverse events were distributed equally.

治疗相关的严重不良事件分布均匀。

interpretation

Pirfenidone did not show superiority over placebo and standard care in this exploratory trial. It cannot be recommended for treating BOS.

在这项探索性试验中，吡非尼酮并未显示出比安慰剂和标准治疗更优越，因此不建议用于治疗闭塞性细支气管炎（BOS）。

Further research is needed to explore other treatments for CLAD to improve long-term outcomes after lung transplantation.

需要进一步的研究来探索慢性肺移植排斥反应（CLAD）的其他治疗方法，以改善肺移植后的长期结果。