Centre for Human & Applied Physiological Sciences, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK.
Department of Urogynaecology, King's College Hospital, London, UK.
Lancet Respir Med. 2024 Nov;12(11):855-864. doi: 10.1016/S2213-2600(24)00222-4. Epub 2024 Aug 30.
Approximately two-thirds of women with chronic cough have cough-induced stress urinary incontinence (CSUI). We aimed to evaluate the efficacy and safety of gefapixant in reducing CSUI episodes in women with refractory or unexplained chronic cough.
This phase 3b, double-blind, randomised, placebo-controlled trial done at 90 sites in 12 countries enrolled women aged 18 years or older who had chronic cough for at least 1 year, a diagnosis of refractory or unexplained chronic cough, a cough severity visual analogue scale score of 40 mm or more (100 mm maximum), and CSUI for 3 months or more. Participants were randomised 1:1 to oral gefapixant or placebo for 12 weeks. The primary outcome was percentage change from baseline in daily CSUI episodes (7-day average) at week 12. This study is registered with ClinicalTrials.gov (NCT04193176).
From May 10, 2020, to Sept 2, 2022, 375 participants were randomised to and treated with gefapixant 45 mg twice daily (n=185) or placebo (n=190). Mean age was 56·4 years (SD 11·4), with mean chronic cough duration of 5·2 years (SD 6·6) and SUI duration of 4·0 years (SD 5·9). Least-squares mean percentage change from baseline in daily CSUI episodes was -52·8% (95% CI -58·4 to -47·1%) for gefapixant and -41·1% (-46·7 to -35·4%) for placebo (estimated treatment difference: -11·7% [95% CI -19·7 to -3·7]; p=0·004). 129 (70%) of 185 participants who received gefapixant and 71 (37%) of 190 participants who received placebo had at least one adverse event. Safety and tolerability were consistent with previous trials of gefapixant; the most frequent adverse events were taste related.
Gefapixant 45 mg twice daily is the first treatment to show efficacy versus placebo in reducing CSUI episodes in participants with refractory or unexplained chronic cough.
Merck Sharp & Dohme, a subsidiary of Merck & Co.
大约三分之二的慢性咳嗽女性患有咳嗽诱发的压力性尿失禁（CSUI）。我们旨在评估 gefapixant 减少难治性或不明原因慢性咳嗽女性 CSUI 发作的疗效和安全性。
这项在 12 个国家的 90 个地点进行的 3b 期、双盲、随机、安慰剂对照试验纳入了年龄在 18 岁或以上、慢性咳嗽至少 1 年、难治性或不明原因慢性咳嗽诊断、咳嗽严重程度视觉模拟量表评分 40 毫米或以上（最高 100 毫米）和 CSUI 持续 3 个月或以上的女性参与者。参与者按 1:1 随机分配接受 gefapixant 或安慰剂治疗 12 周。主要结局是治疗 12 周时每日 CSUI 发作（7 天平均）的基线变化百分比。本研究在 ClinicalTrials.gov 注册（NCT04193176）。
从 2020 年 5 月 10 日至 2022 年 9 月 2 日，375 名参与者被随机分配并接受 gefapixant 45mg 每日两次（n=185）或安慰剂（n=190）治疗。平均年龄为 56.4 岁（SD 11.4），慢性咳嗽平均持续时间为 5.2 年（SD 6.6），SUI 持续时间为 4.0 年（SD 5.9）。最小二乘均值基线每日 CSUI 发作的百分比变化为 gefapixant 组为-52.8%（95%CI-58.4 至-47.1%），安慰剂组为-41.1%（-46.7 至-35.4%）（估计治疗差异：-11.7%[95%CI-19.7 至-3.7]；p=0.004）。接受 gefapixant 的 185 名参与者中有 129 名（70%）和接受安慰剂的 190 名参与者中有 71 名（37%）至少发生了一次不良事件。安全性和耐受性与 gefapixant 的先前试验一致；最常见的不良事件与味觉有关。
Gefapixant 45mg 每日两次是第一种被证明在减少难治性或不明原因慢性咳嗽患者 CSUI 发作方面优于安慰剂的治疗方法。
默克夏普和多姆，默克公司的子公司。
