PT  - JOURNAL ARTICLE
AU  - Johnson, Miriam J
AU  - Sbizzera, Illary
AU  - Fairhurst, Caroline
AU  - Fazekas, Belinda
AU  - Agar, Meera
AU  - Ekstrom, Magnus
AU  - Currow, David C
TI  - No excess harms from sustained-release morphine: a randomised placebo-controlled trial in chronic breathlessness
AID  - 10.1136/bmjspcare-2019-002009
DP  - 2020 Dec 01
TA  - BMJ Supportive & Palliative Care
PG  - 421--428
VI  - 10
IP  - 4
4099  - http://spcare.bmj.com/content/10/4/421.short
4100  - http://spcare.bmj.com/content/10/4/421.full
SO  - BMJ Support Palliat Care2020 Dec 01; 10
AB  - 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.Trial registration number ACTRN126000806268.