Breathlessness Exertion and Morphine Sulphate

Summary

Breathlessness is an overwhelming symptom affecting tens of thousands of Australians every day. For many people, it persists even when all the underlying causes have been optimally managed (chronic breathlessness). In these circumstances, it often occurs at rest or with minimal exertion. Evidence from a number of clinical studies suggests that a small, regular dose of morphine helps to reduce safely the sensation of breathlessness. However, it is not well established which patients derive more benefit and what is the net clinical effect of this treatment (weighing benefits and harms). This is a phase III, multi-site, randomised, double-blind, placebo-controlled trial with patients with chronic obstructive pulmonary disease (COPD) and severe chronic breathlessness which will explore several important questions: * Are regular, low doses of morphine at four possible doses over 3 weeks more effective than placebo at improving breathlessness? * Does increasing the dose in people who already are experiencing some benefit provide even greater reduction in worst breathlessness? * Does the medication have any effect on daily activity and quality of life? * What are the common or serious side effects of this intervention? * Does the benefit from the medication outweigh the side effects it produces? * Are there specific characteristics of people who are more likely to receive benefit from extended release morphine? Participants will receive once daily extended release morphine (plus laxative, docusate with senna), or placebo (placebo laxative) in addition to their usual medication for up to 3 weeks at increasing doses. Participants will have a medical interview and physical examination to collect some general health information, and baseline measurements including; daily activity, symptoms, and quality of life. A small amount of blood may be required to check eligibility. Further blood samples may be taken at week 1 and 3 to enable testing on how individuals respond to opioids, further consent will be obtained for these samples. Data on benefits, side effects, and medical care will be collected during comprehensive weekly visits. Participants will also fill out a simple diary twice daily for weeks one to three of the study, and for one day each week during an optional 6 month extension stage. The outcome of this study may enable better management of symptoms and activity in people COPD with medicines that are shown to be effective and safe.

Timeline

Start

2016-08-08

Primary completion

2019-12-20

Completion

2019-12-20

Publications

• Ferreira DH, Ryan R, Smyth N, Clow A, Currow DC. The longitudinal impact of low-dose morphine on diurnal cortisol profiles in people with chronic breathlessness and chronic obstructive pulmonary disease (COPD): an exploratory study. Respir Res. 2025 Apr 23;26(1):156. doi: 10.1186/s12931-025-03230-9.
• Ekstrom M, Alameri F, Chang S, Ferreira D, Johnson MJ, Currow DC. Harms of Morphine for Chronic Breathlessness in Relation to Dose, Duration and Titration Phase. J Pain Symptom Manage. 2025 Jun;69(6):581-588.e2. doi: 10.1016/j.jpainsymman.2025.02.020. Epub 2025 Feb 25.
• Altree TJ, Toson B, Loffler KA, Ekstrom M, Currow DC, Eckert DJ. Low-Dose Morphine Does Not Cause Sleepiness in Chronic Obstructive Pulmonary Disease: A Secondary Analysis of a Randomized Clinical Trial. Am J Respir Crit Care Med. 2024 Nov 1;210(9):1113-1122. doi: 10.1164/rccm.202310-1780OC.
• Ekstrom M, Ferreira D, Chang S, Louw S, Johnson MJ, Eckert DJ, Fazekas B, Clark KJ, Agar MR, Currow DC; Australian National Palliative Care Clinical Studies Collaborative. Effect of Regular, Low-Dose, Extended-release Morphine on Chronic Breathlessness in Chronic Obstructive Pulmonary Disease: The BEAMS Randomized Clinical Trial. JAMA. 2022 Nov 22;328(20):2022-2032. doi: 10.1001/jama.2022.20206.
• Ferreira DH, Kochovska S, Honson A, Phillips JL, Currow DC. Two faces of the same coin: a qualitative study of patients' and carers' coexistence with chronic breathlessness associated with chronic obstructive pulmonary disease (COPD). BMC Palliat Care. 2020 May 6;19(1):64. doi: 10.1186/s12904-020-00572-7.
• Currow D, Watts GJ, Johnson M, McDonald CF, Miners JO, Somogyi AA, Denehy L, McCaffrey N, Eckert DJ, McCloud P, Louw S, Lam L, Greene A, Fazekas B, Clark KC, Fong K, Agar MR, Joshi R, Kilbreath S, Ferreira D, Ekstrom M; Australian national Palliative Care Clinical Studies Collaborative (PaCCSC). A pragmatic, phase III, multisite, double-blind, placebo-controlled, parallel-arm, dose increment randomised trial of regular, low-dose extended-release morphine for chronic breathlessness: Breathlessness, Exertion And Morphine Sulfate (BEAMS) study protocol. BMJ Open. 2017 Jul 17;7(7):e018100. doi: 10.1136/bmjopen-2017-018100.

Drugs

Indications