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No excess harms from sustained-release morphine : A randomised placebo-controlled trial in chronic breathlessness

Johnson, Miriam J. ; Sbizzera, Illary ; Fairhurst, Caroline ; Fazekas, Belinda ; Agar, Meera ; Ekstrom, Magnus LU and Currow, David C. (2019) In BMJ Supportive and Palliative Care
Abstract

Objectives: We aimed to identify and evaluate: (1) treatment-emergent adverse events (TEAE (worse or new since baseline)) and the subgroup of severe TEAEs in a placebo-controlled 7-day randomised trial of regular, low-dose, sustained-release oral morphine for chronic breathlessness and (2) clinical characteristics associated with TEAE. 

Methods: Safety analysis of trial data. Adults with chronic breathlessness (modified Medical Research Council breathlessness score ≥2) due to heart or lung disease, or cancer, not on regular opioids were eligible. Symptoms associated with opioids (TEAE of special interest) were systematically sought using Common Terminology Criteria for Adverse Events (CTCAE) grading. Other harms could be reported... (More)

Objectives: We aimed to identify and evaluate: (1) treatment-emergent adverse events (TEAE (worse or new since baseline)) and the subgroup of severe TEAEs in a placebo-controlled 7-day randomised trial of regular, low-dose, sustained-release oral morphine for chronic breathlessness and (2) clinical characteristics associated with TEAE. 

Methods: Safety analysis of trial data. Adults with chronic breathlessness (modified Medical Research Council breathlessness score ≥2) due to heart or lung disease, or cancer, not on regular opioids were eligible. Symptoms associated with opioids (TEAE of special interest) were systematically sought using Common Terminology Criteria for Adverse Events (CTCAE) grading. Other harms could be reported at any time. The relationship between characteristics and presence of ≥1 TEAE of special interest was explored using univariable logistic regression analyses. 

Results: 1449/5624 (26%) Adverse Events from 279 participants were TEAE of which 150/1449 (10%) were severe (CTCAE grades 3-5). 1086/5624 (75%) were events of special interest of which 41/1086 (4%) were severe. Compared with placebo, morphine was not associated with more TEAE or severe TEAE of special interest (TEAE: OR 0.53, 95% CI 0.21 to 1.38, p=0.20; severe TEAE: OR 0.96, 95% CI 0.27 to 3.41, p=0.95) nor with CTCAE severity grade (χ2=4.39, p=0.50). Among the 26/150 (17%) with severe TEAEs, study withdrawal was more common in the morphine arm (18/26 (69%) morphine arm; 8/26 (30%) placebo arm). None of the severe TEAEs was a respiratory harm. 

Conclusions: Severe morphine-associated toxicity was uncommon and not associated with study arm. Clinical consequences were minor and self-limiting. 

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author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
chronic breathlessness, dyspnea, harms, Morphine, safety
in
BMJ Supportive and Palliative Care
publisher
BMJ Publishing Group
external identifiers
  • scopus:85075021005
  • pmid:31719052
ISSN
2045-435X
DOI
10.1136/bmjspcare-2019-002009
language
English
LU publication?
yes
id
587f081b-164d-4e00-9ebe-55fa6fd82133
date added to LUP
2019-12-09 13:27:19
date last changed
2020-04-27 10:03:13
@article{587f081b-164d-4e00-9ebe-55fa6fd82133,
  abstract     = {<p>Objectives: We aimed to identify and evaluate: (1) treatment-emergent adverse events (TEAE (worse or new since baseline)) and the subgroup of severe TEAEs in a placebo-controlled 7-day randomised trial of regular, low-dose, sustained-release oral morphine for chronic breathlessness and (2) clinical characteristics associated with TEAE. </p><p>Methods: Safety analysis of trial data. Adults with chronic breathlessness (modified Medical Research Council breathlessness score ≥2) due to heart or lung disease, or cancer, not on regular opioids were eligible. Symptoms associated with opioids (TEAE of special interest) were systematically sought using Common Terminology Criteria for Adverse Events (CTCAE) grading. Other harms could be reported at any time. The relationship between characteristics and presence of ≥1 TEAE of special interest was explored using univariable logistic regression analyses. </p><p>Results: 1449/5624 (26%) Adverse Events from 279 participants were TEAE of which 150/1449 (10%) were severe (CTCAE grades 3-5). 1086/5624 (75%) were events of special interest of which 41/1086 (4%) were severe. Compared with placebo, morphine was not associated with more TEAE or severe TEAE of special interest (TEAE: OR 0.53, 95% CI 0.21 to 1.38, p=0.20; severe TEAE: OR 0.96, 95% CI 0.27 to 3.41, p=0.95) nor with CTCAE severity grade (χ<sup>2</sup>=4.39, p=0.50). Among the 26/150 (17%) with severe TEAEs, study withdrawal was more common in the morphine arm (18/26 (69%) morphine arm; 8/26 (30%) placebo arm). None of the severe TEAEs was a respiratory harm. </p><p>Conclusions: Severe morphine-associated toxicity was uncommon and not associated with study arm. Clinical consequences were minor and self-limiting. </p>},
  author       = {Johnson, Miriam J. and Sbizzera, Illary and Fairhurst, Caroline and Fazekas, Belinda and Agar, Meera and Ekstrom, Magnus and Currow, David C.},
  issn         = {2045-435X},
  language     = {eng},
  month        = {11},
  publisher    = {BMJ Publishing Group},
  series       = {BMJ Supportive and Palliative Care},
  title        = {No excess harms from sustained-release morphine : A randomised placebo-controlled trial in chronic breathlessness},
  url          = {http://dx.doi.org/10.1136/bmjspcare-2019-002009},
  doi          = {10.1136/bmjspcare-2019-002009},
  year         = {2019},
}