Efficacy and safety of gefapixant in women with chronic cough and cough-induced stress urinary incontinence: a phase 3b, randomised, multicentre, double-blind, placebo-controlled trial.

IF 38.7 1区医学 Q1 CRITICAL CARE MEDICINE Lancet Respiratory Medicine Pub Date : 2024-08-30 DOI:10.1016/S2213-2600(24)00222-4

Surinder S Birring, Linda Cardozo, Roger Dmochowski, Peter Dicpinigaitis, Amna Afzal, Carmen La Rosa, Susan Lu, Allison Martin Nguyen, Ruji Yao, Paul A Reyfman

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Abstract

Background: 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.

Methods: 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).

Findings: 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.

Interpretation: 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.

Funding: Merck Sharp & Dohme, a subsidiary of Merck & Co.

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吉法匹克对慢性咳嗽和咳嗽引起的压力性尿失禁妇女的疗效和安全性：3b 期随机、多中心、双盲、安慰剂对照试验。

背景：约有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）。我们旨在评估吉法匹克对减少难治性或不明原因慢性咳嗽女性 CSUI 发作的有效性和安全性：这项 3b 期、双盲、随机、安慰剂对照试验在 12 个国家的 90 个地点进行，招募了年龄在 18 岁或以上、慢性咳嗽至少 1 年、诊断为难治性或不明原因慢性咳嗽、咳嗽严重程度视觉模拟量表评分在 40 毫米或以上（最高 100 毫米）、CSUI 持续 3 个月或以上的女性患者。参与者按 1:1 的比例随机接受口服吉法匹克或安慰剂治疗，疗程为 12 周。主要结果是第12周时每日CSUI发作次数（7天平均值）与基线相比的百分比变化。本研究已在 ClinicalTrials.gov (NCT04193176) 注册：从 2020 年 5 月 10 日到 2022 年 9 月 2 日，375 名参与者被随机分配并接受吉法匹克 45 毫克、每天两次（185 人）或安慰剂（190 人）治疗。平均年龄为56-4岁（SD 11-4），平均慢性咳嗽持续时间为5-2年（SD 6-6），SUI持续时间为4-0年（SD 5-9）。每日 CSUI 发作次数与基线相比的最小二乘法平均百分比变化为：吉法必雄 -52-8%（95% CI -58-4 至 -47-1%），安慰剂 -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）。在接受吉法匹克坦治疗的185名参与者中，有129人（70%）发生了至少一次不良事件；在接受安慰剂治疗的190名参与者中，有71人（37%）发生了至少一次不良事件。安全性和耐受性与之前的吉法匹克坦试验一致；最常见的不良事件与口味有关：头孢匹克45毫克，每日两次，是首个在减少难治性或不明原因慢性咳嗽患者CSUI发作方面显示出疗效的治疗方法：资金来源：默克公司的子公司默克夏普公司（Merck Sharp & Dohme）。

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来源期刊

Lancet Respiratory Medicine RESPIRATORY SYSTEM-RESPIRATORY SYSTEM

CiteScore

87.10

自引率

0.70%

发文量

572

期刊介绍： The Lancet Respiratory Medicine is a renowned journal specializing in respiratory medicine and critical care. Our publication features original research that aims to advocate for change or shed light on clinical practices in the field. Additionally, we provide informative reviews on various topics related to respiratory medicine and critical care, ensuring a comprehensive coverage of the subject. The journal covers a wide range of topics including but not limited to asthma, acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), tobacco control, intensive care medicine, lung cancer, cystic fibrosis, pneumonia, sarcoidosis, sepsis, mesothelioma, sleep medicine, thoracic and reconstructive surgery, tuberculosis, palliative medicine, influenza, pulmonary hypertension, pulmonary vascular disease, and respiratory infections. By encompassing such a broad spectrum of subjects, we strive to address the diverse needs and interests of our readership.