Regular, sustained-release morphine for chronic breathlessness : A multicentre, double-blind, randomised, placebo-controlled trial
Currow, David ; Louw, Sandra ; McCloud, Philip ; Fazekas, Belinda ; Plummer, John ; McDonald, Christine F. ; Agar, Meera ; Clark, Katherine ; McCaffery, Nikki and Ekström, Magnus Pär LU
(2020)
In Thorax
75(1).
p.50-56
- Abstract
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, â € as needed', immediate-release... (More)
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, â € 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.
(Less)
- author
- Currow, David
; Louw, Sandra
; McCloud, Philip
; Fazekas, Belinda
; Plummer, John
; McDonald, Christine F.
; Agar, Meera
; Clark, Katherine
; McCaffery, Nikki
and Ekström, Magnus Pär
LU
- organization
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- chronic breathlessness, placebo study, randomised controlled trial, sustained release morphine, symptom relief
- in
- Thorax
- volume
- 75
- issue
- 1
- pages
- 7 pages
- publisher
- BMJ Publishing Group
- external identifiers
-
- scopus:85076503696
- pmid:31558624
- ISSN
- 0040-6376
- DOI
- 10.1136/thoraxjnl-2019-213681
- language
- English
- LU publication?
- yes
- id
- af92935f-a682-46ca-a8d0-12c53921fd96
- date added to LUP
- 2020-01-03 11:09:02
- date last changed
- 2024-06-26 07:54:30
@article{af92935f-a682-46ca-a8d0-12c53921fd96,
abstract = {{<p>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, â € 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.</p>}},
author = {{Currow, David and Louw, Sandra and McCloud, Philip and Fazekas, Belinda and Plummer, John and McDonald, Christine F. and Agar, Meera and Clark, Katherine and McCaffery, Nikki and Ekström, Magnus Pär}},
issn = {{0040-6376}},
keywords = {{chronic breathlessness; placebo study; randomised controlled trial; sustained release morphine; symptom relief}},
language = {{eng}},
number = {{1}},
pages = {{50--56}},
publisher = {{BMJ Publishing Group}},
series = {{Thorax}},
title = {{Regular, sustained-release morphine for chronic breathlessness : A multicentre, double-blind, randomised, placebo-controlled trial}},
url = {{http://dx.doi.org/10.1136/thoraxjnl-2019-213681}},
doi = {{10.1136/thoraxjnl-2019-213681}},
volume = {{75}},
year = {{2020}},
}