Article Text

Download PDFPDF

Regular, sustained-release morphine for chronic breathlessness: a multicentre, double-blind, randomised, placebo-controlled trial
  1. David Currow1,2,
  2. Sandra Louw3,
  3. Philip McCloud3,
  4. Belinda Fazekas1,2,
  5. John Plummer2,
  6. Christine F McDonald4,5,
  7. Meera Agar1,
  8. Katherine Clark6,7,
  9. Nikki McCaffery2,8,
  10. Magnus Pär Ekström1,9
  11. On behalf of the Australian National Palliative Care Clinical Studies Collaborative (PaCCSC)
  1. 1 IMPACCT, Faculty of Heath, University of Technology Sydney, Sydney, New South Wales, Australia
  2. 2 College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
  3. 3 McCloud Consulting Group, Sydney, New South Wales, Australia
  4. 4 Respiratory and Sleep Medicine, Austin Health, Heidelberg, Victoria, Australia
  5. 5 University of Melbourne, Melbourne, Victoria, Australia
  6. 6 Northern Sydney Local Health District, Saint Leonards, New South Wales, Australia
  7. 7 Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia
  8. 8 Deakin Health Economics, Deakin University Faculty of Health, Burwood, Victoria, Australia
  9. 9 Department of Clinical Sciences, Division of Respiratory Medicine & Allergology, Lund University, Lund, Sweden
  1. Correspondence to Professor David Currow, Faculty of Heath, University of Technology Sydney, Sydney, NSW 2007, Australia; david.currow{at}


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.

  • randomised controlled trial
  • sustained release morphine
  • chronic breathlessness
  • symptom relief
  • placebo study

Statistics from


  • Contributors All the authors contributed to the conception, writing and final approval of this manuscript.

  • Funding Funding was provided for the study by the Australian Government Department of Health through the National Palliative Care Program.

  • Disclaimer The funder had no control over study design, conduct, analysis, interpretation nor dissemination of results.

  • Competing interests DCC has unrestricted research grant from Mundipharma, is an unpaid member of an advisory board for Helsinn Pharmaceuticals, and has consulted to Specialist Therapeutics and Mayne Pharma, and received intellectual property payments from Mayne Pharma. All other authors declare no competing interests.

  • Patient consent for publication Written consent was given for publication of the results.

  • Ethics approval This study was approved by the Human Research Ethics Committee at each site.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on request from bona fide researchers.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles