A novel reflux inhibitor lesogaberan (AZD3355) as add-on treatment in patients with GORD with persistent reflux symptoms despite proton pump inhibitor therapy: a randomised placebo-controlled trial
A novel reflux inhibitor lesogaberan (AZD3355) as add-on treatment in patients with GORD with persistent reflux symptoms despite proton pump inhibitor therapy: a randomised placebo-controlled trial
复制标题
DOI：
10.1136/gut.2010.235630
复制
发表时间：
2011-09-01
期刊：
影响因子：
24.5
通讯作者：
Denison, Hans
中科院分区：
文献类型：
--
作者：
Boeckxstaens, Guy E.;Beaumont, Hanneke;Denison, Hans
目的 评价新型反流抑制剂来索加贝朗 (AZD3355) 附加治疗对质子泵抑制剂 (PPI) 治疗后仍出现胃食管反流病 (GORD) 症状的患者的疗效和耐受性。 方法 在门诊开展双盲、安慰剂对照、随机、平行组、多中心 IIA 期研究。研究组由 244 名成年患者组成，尽管连续 PPI 治疗≥6 周，但在入组前 7 天或 3 天仍出现至少轻度程度的持续 GORD 症状（胃灼热和/或反流）。除 PPI 治疗外，患者还接受 lesogaberan（65 毫克，每天两次）或安慰剂，为期 4 周。根据反流病问卷，每天记录两次症状强度。治疗反应（定义为在治疗的最后 7 天期间至多 1 个 24 小时内出现不超过轻度程度的胃灼热或反流）。还分析了缓解时间、无症状天数比例和耐受性测量。结果 244 名随机患者中，共有 232 名患者（114 名莱索加贝朗治疗患者和 118 名安慰剂治疗患者）进行了疗效分析。与安慰剂相比，lesogaberan 治疗导致治疗反应者比例显着增加（患者的 16% vs 8%；p=0.026），并且随着时间的推移，反应者的累积比例（对数秩 p=0.0195）显着增加。 Lesogaberan 的耐受性良好：45% 的 lesogaberan 患者和 37% 的安慰剂患者报告不良事件大多为轻度至中度强度。然而，回应者的比例很小。
Objective To evaluate the efficacy and tolerability of add-on treatment with lesogaberan (AZD3355), a novel reflux inhibitor, in patients with persistent gastro-oesophageal reflux disease (GORD) symptoms despite proton pump inhibitor (PPI) therapy.Methods A double-blind, placebo-controlled, randomised, parallel-group, multicentre phase IIA study was carried out in outpatient clinics. The study group comprised 244 adult patients with persistent GORD symptoms (heartburn and/or regurgitation) of at least mild intensity and for 3 days of 7 days before enrolment, despite >= 6 weeks of continuous PPI therapy. Patients received either lesogaberan (65 mg twice daily) or placebo in addition to PPI therapy for a period of 4 weeks. Symptom intensity, based on the Reflux Disease Questionnaire, was recorded twice daily. Treatment response (defined as at most one 24 h period with heartburn or regurgitation of not more than mild intensity during the last 7 days of treatment). Time to response, proportion of symptom-free days and measures of tolerability were also analysed.Results A total of 232 (114 lesogaberan- and 118 placebo-treated patients) of the 244 randomised patients were analysed for efficacy. Treatment with lesogaberan, compared with placebo, resulted in a significantly larger proportion of responders to treatment (16% vs 8% of patients; p=0.026) and cumulative proportion of responders over time (log-rank p=0.0195). Lesogaberan was well tolerated: adverse events of mostly mild to moderate intensity were reported in 45% of patients on lesogaberan and in 37% on placebo.Conclusions Lesogaberan add-on therapy to PPIs significantly improved heartburn and regurgitation symptoms; however, the proportion of responders was small.