Study Design: CTIMP RCT
Disease Area: Respiratory / Palliative Care
Funder: NIHR HTA
Sponsor: Hull University Teaching Hospitals
Chief Investigator: Prof Marie Fallon
Trial Registration: ISRCTN87329095
Morphine and Breathlessness Study (MABEL)
Summary
Chronic breathlessness affects most people with advanced lung cancer, lung fibrosis, COPD (chronic obstructive pulmonary disease; emphysema) and heart failure. People are often disabled by this long-term breathlessness despite best treatments of the underlying condition(s). Chronic breathlessness is frightening for patients and their families. It reduces quality of life, limits how people manage at home with everyday functions (bathing, dressing, preparing food) and at work, increases the number of emergency hospital visits and admissions, and shortens life (although some people may live with chronic breathlessness for many years). Studies of a few days of regular, low doses of ”long-acting” morphine show that this can help reduce chronic breathlessness safely, particularly for people with COPD - but we don't know if it keeps working when used for longer periods, or if it does any harm in the longer term. At present, some doctors will prescribe morphine for breathlessness and others won’t.
What we plan to do
We will test if regular, low dose morphine capsules regularly twice a day are better than placebo (dummy) ones for chronic breathlessness and whether morphine improves daily activity in 158 people. We will also see any effect on the need to go to Accident & Emergency, call an ambulance, phone a GP after hours, or go into hospital. We will cost this care and, if it works, find the best ways to provide long-acting morphine to people who need it and would safely benefit from it.
People with fully treated disease still causing chronic breathlessness participating in the study will be chosen at random to have either morphine or a placebo capsule twice a day for two months. After a week, the dose will be increased if breathlessness isn’t improving and they don’t want to stop because of side-effects. At the end, participants can try morphine as part of their usual care if they want from their GP or usual hospital doctor, while being followed up by the study team. We will judge success on how participants’ worst daily breathlessness feels. We will also measure how much activity they actually do (daily step count), quality of life, how well the person sleeps, possible side-effects, overall ability to function, use of healthcare services and - as the study includes people with serious illness - survival. Family members will also be able to help by completing questionnaires telling us about caring for someone with breathlessness. Alongside the study, we will ask clinicians and study participants about issues which would help or hinder patients to have routine access to regular, low dose morphine for breathlessness if the study shows it is the better treatment.
What we will achieve
If the study shows that morphine helps, and doesn’t harm, we want all suitable patients to be able to have access to it. However, we know some doctors, nurses, patients and carers may have concerns about morphine, so we will find out what support is needed to make sure morphine is available, and used carefully and in accordance with the evidence.
Chief Investigator
Prof Marie Fallon - Chair of Palliative Medicine - Edinburgh Cancer Research Centre (IGMM), University of Edinburgh
HHTU Study team
Bronwen Williams - Operations Manager
Sarah Sumpter - Data Manager
Prof Judith Cohen - Director
John Turgoose - Information Systems Manager
Dr Matthew Northgraves - Trial Manager
Dr Mahboobeh Haji-Sadeghi - Trial Manager
Martina Santarelli - Trial Manager
Anesu Matamba - Trial Coordinator
Paul Bradley - Trial Coordinator
Vic Christie - Trial Coordinator
Amy Porter - Trial Administrator
Dr Chao Huang - Statistician
Steve Howe - Data Manager
Beccy Acaster - Data Manager
Charlotte Thompson - Trial Coordinator
Collaborators
Prof Miriam Johnson Academic Lead (former Chief Investigator) - Wolfson Palliative Care Research Centre, Hull York Medical School, University of Hull
Prof John Norrie Co-applicant - Edinburgh Clinical Trials Unit (ECTU), Usher Institute, University of Edinburgh
Catriona Keerie Trial Statistician, blinded - ECTU
Sharon Tuck Trial Statistician, unblinded - ECTU
Dr Peter Hall Health Economist - ECTU
James Illingworth Sponsor - Hull University Teaching Hospitals Trust (HUTH)
Leanne Cox Sponsor - HUTH
Grant Constable Sponsor - HUTH
Rhian Horne Clinical Trial Pharmacist - HUTH
Dr Mark Pearson Co-applicant - Wolfson Palliative Care Research Centre, Hull York Medical School
Dr Sabrina Bajwah Co-applicant - Cicely Saunders Institute, King’s College London
Dr Nazia Chaudhuri Co-applicant - University of Ulster)
Prof Irene Higginson Co-applicant - Cicely Saunders Institute, King’s College London
Prof David Currow Co-applicant - Deputy Vice-Chancellor, University of Wollongong, NSW, Australia)
Dr Joanna Bowden Co-Applicant - Fife
Annie Jones PPI Representative
Konstantin Kamenev PPI representative
Email Address
mabel@hyms.ac.uk
Participating sites and their Project Investigators
- Birmingham Dr Gareth Walters
- Hull Dr Simon Hart
- Leeds Alison Boland
- Lothian Dr Gareth Stewart
- Fife Joanna Bowden
- Glasgow Dr Hannah Bayes
- Kings Sabrina Bajwah
- Manchester Dr Pilar Rivera- Ortega
- Leicester Dr Rachael Evans
- Plymouth Jonathan Palmer
- Scarborough Dr Justin Ghosh
- Bristol Dr Shaney Barratt
Publications
Sub Study
Morphine may help people with chronic breathlessness. The MABEL sub-study investigated clinician perspectives on morphine use as part of the Morphine And BrEathLessness (MABEL) trial to assess the effectiveness and cost-effectiveness of morphine in chronic Breathlessness.
A mixed-methods Normalisation Process Theory was used to organise data collection and analysis of clinicians’ perspectives on morphine use for chronic breathlessness. Clinicians completed a Learning Needs Assessment (LNA) survey and a Modified Normalisation Measurement instrument (NoMAD) at two time-points (immediately and four months post-training) to identify implementation barriers and facilitators.
59 clinicians were recruited from 12 sites and included 28 doctors; 22 non-prescriber nurses; 6 prescriber nurses; 3 other healthcare professionals. Of these 90% were hospital-based. 74% were female and years of experience ranged from 1 to >15 years.
In conclusion, clinicians recognised learning needs about the safe prescription and management of morphine for chronic breathlessness in practice. The potential value of morphine is recognised, but the lack of training and resources are barriers to implementation.
Study Team
Dr Mark Pearson Reader in Implementation Science - Hull York Medical School
Florence Reedy Research Assistant - Hull York Medical School
Ahmed Mohammed Research Assistant - Hull York Medical School
Kathryn Date Trial Manager - HHTU
Dissemination
Peer-reviewed paper:
Reedy, F., Pearson, M., Greenley, S., Clark, J., Currow, D.C, Bajwah, S., Fallon, M. & Johnson, M.J.J (2021) Professionals’, patients’, and families’ views on the use of opioids for breathlessness: A systematic review using the framework method and pillar process. Palliative Medicine 35 (8) 1421-1433
Conference presentations:
Reedy, F., Pearson, M., Greenley, S., Clark, J., Currow, D.C, Bajwah, S., Fallon, M. & Johnson, M.J.J Professionals’, patients’, and families’ views on the use of opioids for breathlessness: A systematic review using the framework method and pillar process. Palliative Care Congress 2021
Mohamed, A., Date, K., Williams, B., Bajwah, S., Johnson, M., Fallon, M. & Pearson, M. Clinicians’ perspectives on morphine use in chronic breathlessness: Findings from an implementation survey. Palliative Care Congress 2023