Modified-release morphine or placebo for chronic breathlessness: the MABEL trial protocol

Chronic breathlessness, a persistent and disabling symptom despite optimal treatment of underlying causes, is frightening with serious widespread impact on patients their carers. Clinical guidelines support the use morphine for relief chronic breathlessness in common long-term conditions, but questions remain around clinical effectiveness, safety longer-term (>7 days) administration. This trial will evaluate effectiveness low-dose oral modified release breathlessness. multicentre, parallel group, double-blind, randomised, placebo-controlled trial. Participants [n=158] be opioid-naïve due to heart or lung disease, cancer post-COVID-19. randomised 1:1 5 mg modified-release morphine/placebo twice daily docusate/placebo 100 56 days. Non-responders at Day 7 dose escalate 10 15. The primary endpoint (Day 28) measure worst severity (past 24 h). Secondary outcome measures include cough, distress, pain; functional status; physical activity; quality life; early identification management morphine-related side effects. At 56, participants may opt take open-label, as part usual care complete quarterly toxicity questionnaires. study powered able reject null hypothesis an embedded normalisation process theory-informed qualitative sub-study explore adoption first-line pharmacological practice if effective.