Introduction Morphine may decrease the intensity of chronic breathlessness but data from a large randomised controlled trial (RCT) are lacking. This first, large, parallel-group trial aimed to test the efficacy and safety of regular, low-dose, sustained-release (SR) morphine compared with placebo for chronic breathlessness. Methods Multisite (14 inpatient and outpatient cardiorespiratory and palliative care services in Australia), parallel-arm, double-blind RCT. Adults with chronic breathlessness (modified Medical Research Council≥2) were randomised to 20 mg daily oral SR morphine and laxative (intervention) or placebo and placebo laxative (control) for 7 days. Both groups could take ≤6 doses of 2.5 mg, ‘as needed’, immediate-release morphine (≤15 mg/24 hours) as required by the ethics review board. The primary endpoint was change from baseline in intensity of breathlessness now (0–100 mm visual analogue scale; two times per day diary) between groups. Secondary endpoints included: worst, best and average breathlessness; unpleasantness of breathlessness now, fatigue; quality of life; function; and harms. Results Analysed by intention-to-treat, 284 participants were randomised to morphine (n=145) or placebo (n=139). There was no difference between arms for the primary endpoint (mean difference −0.15 mm (95% CI −4.59 to 4.29; p=0.95)), nor secondary endpoints. The placebo group used more doses of oral morphine solution during the treatment period (mean 8.7 vs 5.8 doses; p=0.001). The morphine group had more constipation and nausea/vomiting. There were no cases of respiratory depression nor obtundation. Conclusion No differences were observed between arms for breathlessness, but the intervention arm used less rescue immediate-release morphine. Trial registration number ACTRN12609000806268.

中文翻译：

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用于慢性呼吸困难的常规缓释吗啡：一项多中心、双盲、随机、安慰剂对照试验

简介 吗啡可能会降低慢性呼吸困难的强度，但缺乏来自大型随机对照试验 (RCT) 的数据。这是首个大型平行组试验，旨在测试常规、低剂量、缓释 (SR) 吗啡与安慰剂相比对慢性呼吸困难的疗效和安全性。方法 多站点（澳大利亚 14 个住院和门诊心肺和姑息治疗服务）、平行臂、双盲 RCT。患有慢性呼吸困难的成人（修改后的医学研究委员会≥2）随机接受 20 mg 每日口服 SR 吗啡和泻药（干预）或安慰剂和安慰剂泻药（对照）7 天。根据伦理审查委员会的要求，两组都可以服用≤6 剂 2.5 毫克的速释吗啡（≤15 毫克/24 小时）。主要终点是现在各组之间呼吸困难强度（0-100 毫米视觉模拟量表；每天两次日记）相对于基线的变化。次要终点包括：最差、最好和平均呼吸困难；现在呼吸困难，疲劳; 生活质量; 功能; 和伤害。结果 通过意向治疗分析，284 名参与者被随机分配至吗啡（n=145）或安慰剂（n=139）。在主要终点（平均差异 -0.15 mm（95% CI -4.59 至 4.29；p=0.95））和次要终点方面，两组之间没有差异。安慰剂组在治疗期间使用更多剂量的口服吗啡溶液（平均 8.7 对 5.8 剂量；p=0.001）。吗啡组有更多的便秘和恶心/呕吐。没有呼吸抑制或迟钝的病例。结论 两组之间没有观察到呼吸困难的差异，但干预组使用较少的急救立即释放吗啡。试用注册号 ACTRN12609000806268。