Extended-Release Morphine for Chronic Breathlessness in Pulmonary Arterial Hypertension—A Randomized, Double-Blind, Placebo-Controlled, Crossover Study
Ferreira, Diana H. ; Ekström, Magnus LU
; Sajkov, Dimitar
; Vandersman, Zac
; Eckert, Danny J.
and Currow, David C.
(2018)
In Journal of Pain and Symptom Management
56(4).
p.483-492
- Abstract
Context: Pulmonary arterial hypertension (PAH) affects people of all ages and is associated with poor prognosis. Chronic breathlessness affects almost all people with PAH. Objectives: This randomized, placebo-controlled, double-blind, crossover study aimed to evaluate the effects of regular, low-dose, extended-release (ER) morphine for PAH-associated chronic breathlessness. Methods: Participants with PAH-associated chronic breathlessness were randomized to 1) seven days of ER morphine 20 mg, 2) seven-day washout, and 3) seven days of identically looking placebo, or vice versa. Primary end points were breathlessness “right now”—morning and evening—measured with a Visual Analogue Scale. Secondary end points included additional... (More)
Context: Pulmonary arterial hypertension (PAH) affects people of all ages and is associated with poor prognosis. Chronic breathlessness affects almost all people with PAH. Objectives: This randomized, placebo-controlled, double-blind, crossover study aimed to evaluate the effects of regular, low-dose, extended-release (ER) morphine for PAH-associated chronic breathlessness. Methods: Participants with PAH-associated chronic breathlessness were randomized to 1) seven days of ER morphine 20 mg, 2) seven-day washout, and 3) seven days of identically looking placebo, or vice versa. Primary end points were breathlessness “right now”—morning and evening—measured with a Visual Analogue Scale. Secondary end points included additional breathlessness measures, quality of life, function, harms, and blinded treatment preference (ACTRN12609000209291). Results: Within a period of seven years, 50 patients were assessed in detail and 23 (46%) were randomized (despite broad eligibility criteria). Four participants withdrew while taking morphine. Nineteen participants completed the study. Breathlessness “right now” was higher on morphine compared with placebo both for morning [mean (M) ± SD 31.7 ± 25 mm vs. 26.9 ± 22 mm; effect size (80% CI) = −0.22 (−0.6 to 0.2)] and evening [(M ± SD 33.5 ± 28 mm vs. 25.6 ± 21 mm; effect size (80% CI) = −0.33 (−0.8 to 0.1)]. All secondary measures of breathlessness were higher with morphine as were nausea and constipation. Conclusion: This study does not support a Phase III study of ER morphine for people with PAH-associated chronic breathlessness. Recruiting to the target sample size was difficult, the direction of effect in every measure of breathlessness favored placebo and morphine generated more harms.
(Less)
- author
- Ferreira, Diana H.
; Ekström, Magnus
LU
; Sajkov, Dimitar
; Vandersman, Zac
; Eckert, Danny J.
and Currow, David C.
- organization
- publishing date
- 2018
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Chronic breathlessness, effectiveness study, morphine, pulmonary arterial hypertension, randomized controlled trial
- in
- Journal of Pain and Symptom Management
- volume
- 56
- issue
- 4
- pages
- 10 pages
- publisher
- Elsevier
- external identifiers
-
- scopus:85053081567
- pmid:30031217
- ISSN
- 0885-3924
- DOI
- 10.1016/j.jpainsymman.2018.07.010
- language
- English
- LU publication?
- yes
- id
- 89cd1f00-38ba-413a-a177-5819a2a5b997
- date added to LUP
- 2018-10-10 10:21:48
- date last changed
- 2024-08-20 00:58:22
@article{89cd1f00-38ba-413a-a177-5819a2a5b997,
abstract = {{<p>Context: Pulmonary arterial hypertension (PAH) affects people of all ages and is associated with poor prognosis. Chronic breathlessness affects almost all people with PAH. Objectives: This randomized, placebo-controlled, double-blind, crossover study aimed to evaluate the effects of regular, low-dose, extended-release (ER) morphine for PAH-associated chronic breathlessness. Methods: Participants with PAH-associated chronic breathlessness were randomized to 1) seven days of ER morphine 20 mg, 2) seven-day washout, and 3) seven days of identically looking placebo, or vice versa. Primary end points were breathlessness “right now”—morning and evening—measured with a Visual Analogue Scale. Secondary end points included additional breathlessness measures, quality of life, function, harms, and blinded treatment preference (ACTRN12609000209291). Results: Within a period of seven years, 50 patients were assessed in detail and 23 (46%) were randomized (despite broad eligibility criteria). Four participants withdrew while taking morphine. Nineteen participants completed the study. Breathlessness “right now” was higher on morphine compared with placebo both for morning [mean (M) ± SD 31.7 ± 25 mm vs. 26.9 ± 22 mm; effect size (80% CI) = −0.22 (−0.6 to 0.2)] and evening [(M ± SD 33.5 ± 28 mm vs. 25.6 ± 21 mm; effect size (80% CI) = −0.33 (−0.8 to 0.1)]. All secondary measures of breathlessness were higher with morphine as were nausea and constipation. Conclusion: This study does not support a Phase III study of ER morphine for people with PAH-associated chronic breathlessness. Recruiting to the target sample size was difficult, the direction of effect in every measure of breathlessness favored placebo and morphine generated more harms.</p>}},
author = {{Ferreira, Diana H. and Ekström, Magnus and Sajkov, Dimitar and Vandersman, Zac and Eckert, Danny J. and Currow, David C.}},
issn = {{0885-3924}},
keywords = {{Chronic breathlessness; effectiveness study; morphine; pulmonary arterial hypertension; randomized controlled trial}},
language = {{eng}},
number = {{4}},
pages = {{483--492}},
publisher = {{Elsevier}},
series = {{Journal of Pain and Symptom Management}},
title = {{Extended-Release Morphine for Chronic Breathlessness in Pulmonary Arterial Hypertension—A Randomized, Double-Blind, Placebo-Controlled, Crossover Study}},
url = {{http://dx.doi.org/10.1016/j.jpainsymman.2018.07.010}},
doi = {{10.1016/j.jpainsymman.2018.07.010}},
volume = {{56}},
year = {{2018}},
}