腹腔镜抗反流手术治疗特发性肺纤维化（WRAP-IPF）：一项多中心、随机、对照的 2 期临床试验。
Laparoscopic anti-reflux surgery for the treatment of idiopathic pulmonary fibrosis (WRAP-IPF): a multicentre, randomised, controlled phase 2 trial.
机构信息
Department of Medicine, University of Washington, Seattle, WA, USA.
Department of Surgery, University of Washington, Seattle, WA, USA.
出版信息
Lancet Respir Med. 2018 Sep;6(9):707-714. doi: 10.1016/S2213-2600(18)30301-1. Epub 2018 Aug 9.
BACKGROUND
Abnormal acid gastro-oesophageal reflux (GER) is hypothesised to play a role in progression of idiopathic pulmonary fibrosis (IPF). We aimed to determine whether treatment of abnormal acid GER with laparoscopic anti-reflux surgery reduces the rate of disease progression.
METHODS
The WRAP-IPF trial was a randomised controlled trial of laparoscopic anti-reflux surgery in patients with IPF and abnormal acid GER recruited from six academic centres in the USA. We enrolled patients with IPF, abnormal acid GER (DeMeester score of ≥14·7; measured by 24-h pH monitoring) and preserved forced vital capacity (FVC). We excluded patients with a FVC below 50% predicted, a FEV/FVC ratio of less than 0·65, a history of acute respiratory illness in the past 12 weeks, a body-mass index greater than 35, and known severe pulmonary hypertension. Concomitant therapy with nintedanib and pirfenidone was allowed. The primary endpoint was change in FVC from randomisation to week 48, in the intention-to-treat population with mixed-effects models for repeated measures. This trial is registered with ClinicalTrials.gov, number NCT01982968.
FINDINGS
Between June 1, 2014, and Sept 30, 2016, we screened 72 patients and randomly assigned 58 patients to receive surgery (n=29) or no surgery (n=29). 27 patients in the surgery group and 20 patients in the no surgery group had an FVC measurement at 48 weeks (p=0·041). Intention-to-treat analysis adjusted for baseline anti-fibrotic use demonstrated the adjusted rate of change in FVC over 48 weeks was -0·05 L (95% CI -0·15 to 0·05) in the surgery group and -0·13 L (-0·23 to -0·02) in the non-surgery group (p=0·28). Acute exacerbation, respiratory-related hospitalisation, and death was less common in the surgery group without statistical significance. Dysphagia (eight [29%] of 28) and abdominal distention (four [14%] of 28) were the most common adverse events after surgery. There was one death in the surgery group and four deaths in the non-surgery group.
INTERPRETATION
Laparoscopic anti-reflux surgery in patients with IPF and abnormal acid GER is safe and well tolerated. A larger, well powered, randomised controlled study of anti-reflux surgery is needed in this population.
FUNDING
US National Institutes of Health National Heart, Lung and Blood Institute.
背景
胃酸胃食管反流异常被认为在特发性肺纤维化（IPF）的进展中起作用。我们旨在确定腹腔镜抗反流手术治疗异常胃酸 GER 是否能降低疾病进展的速度。
方法
WRAP-IPF 试验是在美国六个学术中心招募的 IPF 合并异常胃酸 GER（24 小时 pH 监测的 DeMeester 评分≥14.7）和保留用力肺活量（FVC）的患者进行的腹腔镜抗反流手术的随机对照试验。我们纳入了 IPF、异常胃酸 GER（预测 FVC 低于 50%、FEV/FVC 比小于 0.65、过去 12 周内有急性呼吸道疾病史、体重指数大于 35 和已知严重肺动脉高压的患者）。允许同时使用尼达尼布和吡非尼酮进行治疗。主要终点是意向治疗人群在 48 周时的 FVC 变化，使用重复测量的混合效应模型进行分析。这项试验在 ClinicalTrials.gov 上注册，编号为 NCT01982968。
结果
2014 年 6 月 1 日至 2016 年 9 月 30 日，我们共筛查了 72 例患者，将 58 例患者随机分为手术组（n=29）和非手术组（n=29）。手术组 27 例和非手术组 20 例患者在 48 周时进行了 FVC 测量（p=0.041）。在调整了基线抗纤维化药物使用的意向治疗分析中，手术组 48 周时 FVC 的变化率为 -0.05 L（95%CI-0.15 至 0.05），而非手术组为 -0.13 L（-0.23 至-0.02）（p=0.28）。手术组的急性加重、与呼吸相关的住院和死亡较少，但无统计学意义。手术后最常见的不良事件是吞咽困难（28 例中的 8 例，29%）和腹胀（28 例中的 4 例，14%）。手术组有 1 例死亡，非手术组有 4 例死亡。
结论
腹腔镜抗反流手术治疗 IPF 合并异常胃酸 GER 是安全且耐受良好的。在这一人群中，需要进行更大规模、更有力的、随机对照的抗反流手术研究。
资助
美国国立卫生研究院国家心肺血液研究所。
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