Chronic breathlessness is common and very disabling in people with heart and lung conditions and cancer.
We aimed to see if 10 to 20mg per day of oral morphine is better than dummy capsules at improving breathlessness. This 2-month trial was designed to set the new standard of care if positive. Morphine and Breathlessness (MABEL) is a collaboration between the Hull York Medical School (University of Hull), the Universities of Edinburgh, and Kings College London, and conducted by the Hull Health Trials Unit.
MABEL is registered with the ISRCTN.
What did we do?
MABEL trial participants had moderate to severe breathlessness due to various conditions, mainly COPD and Interstitial Lung Disease. They were chosen at random to receive a small daily dose of morphine or an identical dummy capsule twice a day for 56 days. They also received a laxative capsule and an identical dummy capsule every day, to prevent the common side-effect of constipation. Patients and carers were involved in and advised on the research processes from beginning to end. We asked everyone to complete questionnaires about their breathlessness and other symptoms (pain, cough), quality of life at one and two months later. We also measured the amount of daily physical activity at the study start and one month later.
Study doctors and nurses were trained to monitor and manage known morphine-related side-effects throughout the trial, but especially during the first week, and the week following an optional dose-increase.
View the published protocol Modified-release morphine or placebo for chronic breathlessness: the MABEL trial protocol.
What did we find?
We examined information from 140 participants recruited from 11 UK sites.
At one month follow-up, compared with dummy medication:
- There was no noticeable benefit for breathlessness
- There was no noticeable benefit for any other measure, except for levels of physical activity - people taking morphine on average completed about 10 more minutes of moderate-vigorous exercise per day.
By two-months’ follow-up, there was a noticeable improvement in the worst daily cough.
Overall, morphine was reasonably well tolerated. Although more people stopped taking the study medication in the morphine group than in the dummy medication group, fewer did this than in similar studies. Constipation, nausea and vomiting were more common in people taking morphine, but these symptoms were mainly controlled and resolved within the first week, except for constipation. Importantly, people taking morphine did not have more confusion, memory problems or sleepiness than those taking dummy medication, and there were no morphine-related deaths. More people in the morphine arm were admitted to hospital during the study, although in most cases, this was not thought to be due to the morphine by their doctor.
The main paper findings can be found in the Lancet Respiratory Medicine Journal: Morphine for chronic breathlessness (MABEL) in the UK: a multi-site, parallel-group, dose titration, double-blind, randomised, placebo-controlled trial.
With regard to the potential impact on NHS costs (using morphine-related hospital admissions only), morphine has a high likelihood of being cost-effective.
The health economic evaluation can be found here - Morphine for chronic breathlessness (MABEL) in the UK: a health economic evaluation of a multisite, parallel-group, dose titration, double-blind, randomised, placebo-controlled trial.
Visit the MABEL website