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

Area of Science:

• Palliative Care
• Clinical Pharmacology
• Respiratory Medicine

Background:

• Chronic breathlessness significantly impacts patients and carers despite optimal treatment.
• Clinical guidelines suggest morphine for chronic breathlessness, but effectiveness and safety data are limited.
• There is a need to evaluate low-dose oral modified-release morphine for this debilitating symptom.

Purpose of the Study:

• To evaluate the effectiveness of low-dose oral modified-release morphine in relieving chronic breathlessness.
• To assess the safety and tolerability of modified-release morphine for chronic breathlessness.
• To explore the adoption of morphine as a first-line treatment in clinical practice.

Main Methods:

• A multicentre, double-blind, randomised, placebo-controlled trial involving 158 opioid-naïve participants.
• Participants received either modified-release morphine (5mg or 10mg) or placebo twice daily for 56 days.
• Primary endpoint was worst breathlessness severity at Day 28; secondary outcomes included cough, distress, pain, and quality of life.

Main Results:

• The study is powered to detect a significant difference in breathlessness severity.
• Secondary outcomes include cough, distress, pain, functional status, physical activity, and quality of life.
• Morphine-related side-effects will be monitored for early identification and management.

Conclusions:

• The trial will provide crucial data on the clinical effectiveness and safety of low-dose modified-release morphine for chronic breathlessness.
• Findings may support the integration of morphine into clinical guidelines for managing this symptom.
• A qualitative substudy will explore barriers and facilitators to implementing morphine in clinical practice.