Background Fibrotic hypersensitivity pneumonitis (FHP) is an irreversible lung disease with high morbidity and mortality. We sought to evaluate the safety and effect of pirfenidone on disease progression in such patients. Methods We conducted a single-centre, randomised, double-blinded, placebo-controlled trial in adults with FHP and disease progression. Patients were assigned in a 2:1 ratio to receive either oral pirfenidone (2403 mg/day) or placebo for 52 weeks. The primary end point was the mean absolute change in the per cent predicted forced vital capacity (FVC%). Secondary end points included progression-free survival (PFS, time to a relative decline ≥10% in FVC and/or diffusing capacity of the lung for carbon monoxide (DLCO), acute respiratory exacerbation, a decrease of ≥50 m in the 6 min walk distance, increase or introduction of immunosuppressive drugs or death), change in FVC slope and mean DLCO%, hospitalisations, radiological progression of lung fibrosis and safety. Results After randomising 40 patients, enrolment was interrupted by the COVID-19 pandemic. There was no significant between-group difference in FVC% at week 52 (mean difference −0.76%, 95% CI −6.34 to 4.82). Pirfenidone resulted in a lower rate of decline in the adjusted FVC% at week 26 and improved PFS (HR 0.26, 95% CI 0.12 to 0.60). Results for other secondary end points showed no significant difference between groups. No deaths occurred in the pirfenidone group and one death (respiratory) occurred in the placebo group. There were no treatment-emergent serious adverse events. Conclusions The trial was underpowered to detect a difference in the primary end point. Pirfenidone was found to be safe and improved PFS in patients with FHP. Trial registration mumber [NCT02958917][1]. Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02958917&atom=%2Fthoraxjnl%2F78%2F11%2F1097.atom

中文翻译：

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吡非尼酮治疗纤维化过敏性肺炎：有效性和安全性的双盲、随机临床试验

背景纤维化过敏性肺炎（FHP）是一种不可逆的肺部疾病，具有高发病率和死亡率。我们试图评估吡非尼酮对此类患者疾病进展的安全性和效果。方法 我们对患有 FHP 且疾病进展的成人进行了一项单中心、随机、双盲、安慰剂对照试验。患者按照 2:1 的比例分配接受口服吡非尼酮（2403 毫克/天）或安慰剂治疗，为期 52 周。主要终点是预测用力肺活量百分比 (FVC%) 的平均绝对变化。次要终点包括无进展生存期（PFS、FVC 和/或肺一氧化碳弥散能力 (DLCO) 相对下降 ≥10% 的时间、急性呼吸加重、6 分钟内下降 ≥50 m）步行距离、增加或使用免疫抑制药物或死亡）、FVC 斜率和平均 DLCO% 的变化、住院治疗、肺纤维化的放射学进展和安全性。结果 对 40 名患者进行随机分组后，入组因 COVID-19 大流行而中断。第 52 周时 FVC% 没有显着组间差异（平均差 -0.76%，95% CI -6.34 至 4.82）。吡非尼酮导致第 26 周时调整后的 FVC% 下降率较低，并改善了 PFS（HR 0.26，95% CI 0.12 至 0.60）。其他次要终点的结果显示组间无显着差异。吡非尼酮组未发生死亡，安慰剂组发生 1 例死亡（呼吸系统）。没有出现治疗引起的严重不良事件。结论 该试验不足以检测主要终点的差异。研究发现吡非尼酮对于 FHP 患者是安全的，并且可以改善 PFS。试用注册号[NCT02958917][1]。可根据合理要求提供数据。与研究相关的所有数据都包含在文章中或作为补充信息上传。[1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02958917&atom=%2Fthoraxjnl%2F78%2F11%2F1097.atom