Placebo-controlled RCT: In cardiorespiratory or palliative patients with breathlessness, low-dose morphine did not improve breathlessness at 1 week.
Currow D, Louw S, McCloud P, et al. Regular, sustained-release morphine for chronic breathlessness: a multicentre, double-blind, randomised, placebo-controlled trial. Thorax. 2019 Sep 26. pii: thoraxjnl-2019-213681. doi: 10.1136/thoraxjnl-2019-213681.

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.


Specialty Area Score
Oncology - Palliative and Supportive Care
Oncology - Lung
Hospital Doctor/Hospitalists
Internal Medicine
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