Posted on by Amy Porter

Spotlight Series 03

The MABEL Study

What is the MABEL Study?

Chronic breathlessness is a common, disabling problem for people with long-term lung and heart conditions. Although taking morphine to help with breathlessness has shown promise, studies measuring breathlessness as part of everyday life did not give a clear answer as to whether it helps or not as most didn’t look at long term effects of morphine. The NIHR Health Technology Assessment funded the MABEL Trial, which assessed the effectiveness, economics and safety of long acting oral morphine for breathlessness in people with cardio-respiratory diseases or cancer over 56 days.

When did it run?

The MABEL Trial was originally due to start in early 2020, having gained ethical approval in December 2019. Unfortunately, the COVID-19 pandemic struck leading to a pause in all non-COVID-19 related research in the UK. MABEL finally opened to recruitment in March 2021 and recruited from the 11 sites across England and Scotland below:

  • Birmingham
  • Hull
  • Leeds
  • Lothian
  • Fife
  • Glasgow
  • Kings
  • Manchester
  • Leicester
  • Plymouth
  • Bristol

What did we do?

We conducted the MABEL study to compare the effect 10-20mg of oral morphine taken twice a day as a tablet would have on patients who had chronic moderate to severe long-term breathlessness mainly due to lung conditions.

To evaluate this, half of the participants received morphine and half received a placebo (or dummy) tablet. All participants received a matching laxative tablet, or placebo, taken twice a day as constipation is a common side effect of morphine. Participants completed questionnaires about breathlessness, pain, cough, and quality of life at baseline, 28 and 56 days. We also measured daily physical activity using an ActiGraph monitor at baseline and 28 days.

Study doctors and nurses received training on how to manage morphine-related side-effects before the study began recruitment. We aimed to recruit 158 participants to have enough data at Day 28 (some participants may withdraw from the study before Day 28) to answer the study questions.

We also included two additional exploratory sub-studies. Firstly, healthcare professionals completed surveys and clinical morphine management training to understand what training support for prescribing morphine for chronic breathlessness; and secondly a Study Within A Trial (SWAT) looking at whether an Infographic Summary Sheet given alongside the standard Participant Information Sheet could improve recruitment.

What did we find?

Click each tab to read through the results from each part of the study.

MAIN TRIAL RESULTS

143 participants were recruited and randomised of which 140 were included in the data analysis.  We found:

At 28 days: results for the morphine group compared with the placebo group.

  • There was no clear difference in improving breathlessness between those receiving morphine compared to the placebo group
  • There was significant benefit seen in the level of physical activity with participants in the morphine group, on average, completing 10 minutes more moderate-vigorous physical activity per day than those in the placebo group.

At 56 days:

  • There was a significant improvement in the worst cough experienced by participants in the morphine group than in the placebo group.

Overall, morphine was well tolerated:

  • Constipation, nausea and vomiting were more common in participants taking morphine, but these side effects were usually well managed within the first week.
  • Participants in the morphine group did not have more confusion, memory problems or sleepiness than those in the placebo group
  • About 1 in 10 participants were admitted to hospital at some point during the study. However, except for 3 admissions they were not determined to be a result of taking morphine.

The full results paper is published in The Lancet Respiratory Medicine here: https://doi.org/10.1016/S2213-2600(25)00205-X 

ECONOMIC EVALUATION RESULTS

We found:

  • There were more inpatient admissions but fewer outpatient services used by the morphine group compared to the placebo group
  • Oral morphine for chronic breathlessness is likely to be a cost-effective intervention provided side effects are well managed
  • The effect on outcome is small and cautious interpretation of the results is needed, but signal benefits can be seen.

The full results health economics paper is published in The BMJ open here: https://doi.org/10.1136/bmjopen-2025-102124

PROCESS THEORY-INFORMED EVALUATION (Healthcare Professional surveys and training) RESULTS

The sub study team undertook a Mixed-Methods Normalisation Process Theory (a framework for organising data collection and analysis) of Healthcare Professional (HCP) perspectives on prescribing morphine for patients with chronic breathlessness. HCP completed a Learning Needs Assessment (LNA) survey and a Modified Normalisation Measurement instrument (NoMAD) survey at two time-points (pre training and 4 months after training) to identify barriers and facilitators in prescribing morphine.

59 HCP were recruited from 12 sites. These included 28 doctors; 22 non-prescriber nurses; 6 prescriber nurses; 3 other HCP. Of these 90% were hospital-based and 74% were female. Years of clinical experience ranged from 1 to >15 years.

We found:

  • HCP recognised a need for additional learning about the safe prescription and management of morphine for chronic breathlessness in clinical practice.
  • The potential value of morphine was recognised, but there was a lack of training and resources which are barriers to implementation.

A preprint* of the Process theory-informed evaluation is published on medrxiv here: https://www.medrxiv.org/content/10.1101/2025.06.12.25329502v1

INFOGRAPHIC STUDY WITHIN A TRIAL (SWAT) RESULTS

The SWAT investigated whether an Infographic summary of the trial provided alongside the standard Participant Information Sheet (PIS) would boost/support recruitment to the MABEL study.

We found:

  • The consent rate was 16% higher for those receiving the PIS and Infographic (35.1%) compared to those receiving the PIS alone (18.5%).
  • Although results were not statistically significant, the SWAT has demonstrated a positive trend of improved recruitment rates when using the PIS and the Infographic compared to providing the PIS on its own.

The poster* presented at the International Clinical Trials Methodology Conference can be found here:

ICTMC MABEL SWAT poster (FINAL)

*not peer reviewed

Publications

  1. Modified-release morphine or placebo for chronic breathlessness: the MABEL trial protocol.  ERJ Open Research, ERJ Open Res. 2023 Aug 14;9(4):00167-2023. doi: https://doi.org/10.1183/23120541.00167-2023.
  2. Reedy F, Pearson M, Greenley S, et al. Professionals’, patients’ and families’ views on the use of opioids for chronic breathlessness: A systematic review using the framework method and pillar process. Palliative Medicine Journal. 2021;35(8):1421-1433. https://doi.org/10.1177/02692163211032114
  3. Clinical and cost effectiveness of low dose oral modified release morphine versus placebo on patient-reported worst breathlessness in people with chronic breathlessness: a multi-site, parallel group, dose titration, double-blind, randomised, placebo-controlled trial (MABEL). Lancet Respiratory Medicine 2025, 13 (11): P967–977 Doi: https://doi.org/10.1016/S2213-2600(25)00205-X
  4. Health Economic Evaluation of Low Dose Oral Modified Release Morphine for People with Chronic Breathlessness (MABEL Trial). BMJ Open 2025, 15:e102124
    Doi: https://doi.org/10.1136/bmjopen-2025-102124

PREPRINTS

  1. What enables the safe prescription and monitoring of morphine for chronic breathlessness? Insights from a Normalisation Process Theory-informed implementation survey and interviews with clinicians. https://www.medrxiv.org/content/10.1101/2025.06.12.25329502v1  

Conference Presentations

  1. Oral Presentation. Johnson MJ, Evans RA, Keerie C, Tuck S, Norrie J, Cohen J, Williams B, Hall PS, Atter M, Chaudhuri N, Bajwah S, Higginson IJ, Pearson M, Currow DC, Fallon MT.  ‘The Famous Five’ – Emerging clinical trial data. S111 Effectiveness and cost effectiveness of low dose oral modified release morphine versus placebo on patient-reported worst breathlessness in people with chronic breathlessness: a multi-site, parallel group, double-blind, randomised, placebo-controlled trial (MABEL). British Thoracic Winter Meeting London 2024. Thorax 2024, 79; Issue Suppl 2
  2. Oral Presentation. Reedy F, Pearson M, Greenley S, Clark J, Currow DC, Bajwah S, Fallon MT, Johnson MJ. 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. March 2021.  
  3. Poster Presentation. Northgraves M, Thompson C, Matamba A, Williams B, Ayuba O, Huang C, Johnson MJ, Fallon MT, Cohen J. P-279 Impact on participant recruitment of adding an Infographic to a Patient Information Leaflet in the MABEL trial, a study within a trial (SWAT116). International Clinical Trials, Methodology Conference (ICTMC) 2024 Book of Abstracts P-279 ; 478.
  4. Poster Presentation. Williams B, Matamba A, Northgraves M, Johnson MJ , Fallon MT P-334 The advantages and disadvantages of using a centrally managed ActiGraph distribution system for collecting physical activity data in a multicentre randomised controlled trial. International Clinical Trials Methodology Conference (ICTMC) 2024 Book of Abstracts P-334 ; 541.
  5. Poster Presentation. Thompson C , Williams B, Matamba A, Northgraves M, Johnson MJ , Fallon MT Strategies to encourage site engagement in the Morphine And BrEathLessness Trial (MABEL)