慢性气短是一种持久而且令人残疾的症状，尽管基础原因的最佳治疗，仍然是一种令人害怕且对患者及其护理者具有严重而广泛影响的症状。临床指南支持在常见的长期疾病中使用吗啡缓解慢性气短，但在临床疗效、安全性和更长期（>7天）的用药方面仍存在问题。本试验将评估低剂量口服改良释放吗啡对慢性气短的疗效。这是一项多中心、平行组、双盲、随机、安慰剂对照试验。参与者（n=158）是慢性气短的阿片类药物非经验者，由于心脏或肺部疾病、癌症或新型冠状病毒病引起。参与者将被随机分配为1:1，在56天内口服改良释放吗啡或安慰剂5毫克，每天两次，并同时口服软便药或安慰剂100毫克，每天两次。第7天无反应者将于第15天递增剂量至每天两次口服10毫克的吗啡或安慰剂。主要终点（第28天）的评估指标将是最严重的呼吸困难程度（前24小时）。次要结局指标包括最严重的咳嗽、困扰、疼痛、功能状况、身体活动、生活质量以及早期鉴别和管理与吗啡相关的副作用。在第56天，参与者可以选择使用口服改良释放吗啡作为常规护理的一部分，并完成季度呼吸困难和毒性问卷调查。本研究的设计具备拒绝零假设的能力，同时还将进行一个嵌入的接受度理论为基础的质性子研究，以探索吗啡在临床实践中作为慢性气短的一线药物治疗的采纳程度，如果有效的话。版权所有 © 作者2023年。

Chronic breathlessness, a persistent and disabling symptom despite optimal treatment of underlying causes, is a frightening symptom with serious and widespread impact on patients and their carers. Clinical guidelines support the use of morphine for the relief of chronic breathlessness in common long-term conditions, but questions remain around clinical effectiveness, safety and longer term (>7 days) administration. This trial will evaluate the effectiveness of low-dose oral modified-release morphine in chronic breathlessness. This is a multicentre, parallel group, double-blind, randomised, placebo-controlled trial. Participants (n=158) will be opioid-naïve with chronic breathlessness due to heart or lung disease, cancer or post-coronavirus disease 2019. Participants will be randomised 1:1 to 5 mg oral modified-release morphine/placebo twice daily and docusate/placebo 100 mg twice daily for 56 days. Non-responders at Day 7 will dose escalate to 10 mg morphine/placebo twice daily at Day 15. The primary end-point (Day 28) measure will be worst breathlessness severity (previous 24 h). Secondary outcome measures include worst cough, distress, pain, functional status, physical activity, quality of life, and early identification and management of morphine-related side-effects. At Day 56, participants may opt to take open-label, oral modified-release morphine as part of usual care and complete quarterly breathlessness and toxicity questionnaires. The study is powered to be able to reject the null hypothesis and an embedded normalisation process theory-informed qualitative substudy will explore the adoption of morphine as a first-line pharmacological treatment for chronic breathlessness in clinical practice if effective.Copyright ©The authors 2023.