Background & Aims

Refractory gastroesophageal reflux disease (GERD) reduces quality of life and creates significant financial burden on the health care system. Approximately 30% of patients with GERD who receive label-dose proton pump inhibitors (PPIs) still have symptoms. We performed a trial to evaluate the efficacy and safety of IW-3718, a bile acid sequestrant, as an adjunct to PPI therapy.

Methods

We performed a multicenter, double-blind, placebo-controlled trial, from March 2016 through April 2017, of 280 patients with confirmed GERD. The patients, stratified by esophagitis status, were randomly assigned (1:1:1:1) to groups given placebo or IW-3718 (500, 1000, or 1500 mg) twice daily, with ongoing label-dose PPI. The primary endpoint was percent change from baseline to week 8 in weekly heartburn severity score. We also analyzed percent change from baseline to week 8 in weekly regurgitation frequency score.

Results

Mean changes from baseline to week 8 in weekly heartburn severity scores were reductions of 46.0% in the placebo group, 49.0% in the 500 mg group, 55.1% in the 1000 mg group, and 58.0% in the 1500 mg IW-3718 group (dose-response P = .02). The treatment difference was 11.9% between the 1500 mg IW-3718 and placebo groups (P = .04, analysis of covariance). The mean change in weekly regurgitation frequency score from baseline to week 8 in the 1500 mg IW-3718 vs placebo groups was a reduction of 17.5% (95% confidence interval, reductions of 31.4% to 3.6%). The most common adverse event was constipation (in 8.1% of patients receiving IW-3718 and 7.1% of patients receiving placebo). There were no drug-related serious adverse events.

Conclusions

In a randomized trial of patients with refractory GERD, adding 1500 mg IW-3718 to label-dose PPIs significantly reduced heartburn symptoms compared with adding placebo. Regurgitation symptoms also decreased. IW-3718 was well tolerated. (ClinicalTrials.gov, Number: NCT02637557)

中文翻译：

---

IW-3718在一项随机试验中降低了难治性胃食管反流病患者的烧心严重程度。

背景与目标

难治性胃食管反流病（GERD）降低了生活质量，并给医疗保健系统造成了巨大的经济负担。接受标记剂量质子泵抑制剂（PPI）的GERD患者中约有30％仍然有症状。我们进行了一项试验，以评估IW-3718（一种胆汁酸螯合剂）作为PPI治疗的辅助剂的疗效和安全性。

方法

我们于2016年3月至2017年4月对280名已确诊GERD的患者进行了多中心，双盲，安慰剂对照试验。按食管炎状态分层的患者被随机分配（1：1：1：1）到接受安慰剂或IW-3718（500、1000或1500 mg）的组，每天两次，进行标记剂量的PPI。主要终点是每周烧心严重程度评分从基线到第8周的百分比变化。我们还分析了从每周到第8周从基线到返流频率评分的百分比变化。

结果

从基线到第8周，每周烧心严重程度评分的平均变化为：安慰剂组降低46.0％，500 mg组降低49.0％，1000 mg组降低55.1％，1500 mg IW-3718组降低58.0％（剂量反应P  = .02）。1500 mg IW-3718与安慰剂组之间的治疗差异为11.9％（P  = .04，协方差分析）。1500 mg IW-3718与安慰剂组相比，从基线到第8周的每周反流频率评分的平均变化降低了17.5％（95％置信区间，降低了31.4％至3.6％）。最常见的不良事件是便秘（接受IW-3718的患者为8.1％，接受安慰剂的患者为7.1％）。没有与药物有关的严重不良事件。

结论

在一项难治性GERD患者的随机试验中，与添加安慰剂相比，在标记剂量的PPI中添加1500 mg IW-3718可显着减轻胃灼热症状。反流症状也有所减轻。IW-3718的耐受性良好。（ClinicalTrials.gov，编号：NCT02637557）