Keck School of Medicine, University of Southern California, Los Angeles.
National Heart and Lung Institute, Imperial College London, London.
NEJM Evid. 2023 Aug;2(8):EVIDoa2300083. doi: 10.1056/EVIDoa2300083. Epub 2023 May 22.
There are no approved therapies for cough in patients with idiopathic pulmonary fibrosis (IPF). In this small crossover trial we administered nalbuphine extended-release tablets (NAL ER) as a potential cough therapy for such patients. METHODS: This randomized, double-blind, placebo-controlled, crossover trial involved two 22-day treatment periods (NAL ER→placebo and placebo→NAL ER) separated by a 2-week washout period. NAL ER was started at a dose of 27 mg once daily and was titrated up to 162 mg twice daily at day 16. The primary end point was percent change from baseline in hourly daytime objective cough frequency as measured by an electronic cough monitor. The daytime period was defined as the patient-reported time of awakening and bedtime. Secondary end points included change in objective 24-hour cough frequency, changes in cough frequency, cough severity, and breathlessness, per patient-reported outcomes. RESULTS: A total of 41 patients were randomly assigned and received one or more doses of study medication. There was a 75.1% reduction in daytime objective cough frequency during the NAL ER treatment period versus the placebo treatment period of 22.6%, a 52.5 percentage point placebo-adjusted decrease from baseline (P<0.001) at day 21. There was a 76.1% (95% confidence interval, 83.1 to 69.1) decrease in the 24-hour objective cough frequency with NAL ER, versus a 25.3% (43.9 to 6.7) decrease with placebo, a 50.8 percentage point placebo-adjusted change. Nausea, fatigue, constipation, and dizziness were more common with NAL ER than with placebo. CONCLUSIONS: In this short-term crossover trial, NAL ER reduced cough in individuals with IPF. Larger and longer trials are needed to assess the impact on cough versus drug adverse effects. (Funded by Trevi Therapeutics; ClinicalTrials.gov number, NCT04030026.)
目前针对特发性肺纤维化（IPF）患者的咳嗽尚无获批的治疗方法。在这项小型交叉试验中，我们使用纳布啡缓释片（NAL ER）作为此类患者潜在的咳嗽治疗药物。方法：这是一项随机、双盲、安慰剂对照、交叉试验，包括两个为期 22 天的治疗期（NAL ER→安慰剂和安慰剂→NAL ER），中间间隔 2 周洗脱期。NAL ER 起始剂量为 1 天 1 次，每次 27mg，第 16 天增至 1 天 2 次，每次 162mg。主要终点为电子咳嗽监测仪测量的基础值相比，日间每小时客观咳嗽频率的变化百分比。日间时段定义为患者报告的觉醒时间和就寝时间。次要终点包括客观 24 小时咳嗽频率、咳嗽频率、咳嗽严重程度和呼吸困难的变化，基于患者报告的结果。结果：共有 41 名患者被随机分配并接受了 1 次或多次研究药物治疗。与安慰剂治疗期的 22.6%相比，NAL ER 治疗期的日间客观咳嗽频率降低了 75.1%，与基础值相比下降了 52.5 个百分点（P<0.001），第 21 天。与安慰剂相比，NAL ER 可使 24 小时客观咳嗽频率降低 76.1%（95%置信区间，83.1 至 69.1），而安慰剂组则降低 25.3%（43.9 至 6.7），安慰剂调整后变化为 50.8 个百分点。与安慰剂相比，NAL ER 更常见的不良反应有恶心、疲劳、便秘和头晕。结论：在这项短期交叉试验中，NAL ER 可减轻 IPF 患者的咳嗽。需要更大和更长的试验来评估咳嗽与药物不良反应的影响。（由 Trevi Therapeutics 资助；ClinicalTrials.gov 编号，NCT04030026。）
