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No excess harms from sustained release morphine compared with placebo; findings from a placebo-controlled randomised trial in chronic breathlessness

Johnson, Miriam J; Sbizzera, Illary; Fairhurst, Caroline; Fazekas, Belinda; Agar, Meera R; Ekström, Magnus; Currow, David C

Authors

Illary Sbizzera

Caroline Fairhurst

Belinda Fazekas

Meera R Agar

Magnus Ekström

David C Currow



Abstract

Objectives: We aimed to identify and evaluate i) treatment-emergent adverse events (TEAE [worse or new since baseline]) and the sub-group of severe TEAEs in a placebo-controlled seven-day randomised trial of regular, low-dose, sustained-release oral morphine for chronic breathlessness, and ii) 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%) AEs 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: odds ratio 0.53, 95% CI 0.21 to 1.38, p=0.20; severe TEAE: odds ratio 0.96, 95% CI 0.27 to 3.41, p=0.95) nor with CTCAE severity grade (Χ2=4.39, p=0.50). Amongst 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.

Journal Article Type Article
Print ISSN 2045-435X
Publisher BMJ Publishing Group
Peer Reviewed Peer Reviewed
APA6 Citation Johnson, M. J., Sbizzera, I., Fairhurst, C., Fazekas, B., Agar, M. R., Ekström, M., & Currow, D. C. (in press). No excess harms from sustained release morphine compared with placebo; findings from a placebo-controlled randomised trial in chronic breathlessness. BMJ supportive & palliative care, https://doi.org/10.1136/bmjspcare-2019-002009
DOI https://doi.org/10.1136/bmjspcare-2019-002009

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