Consenting adults (1:1, stratified by site and causal disease) with a modified Medical Research Council breathlessness score of 3 or higher due to cardiorespiratory conditions were randomly assigned to receive 5–10 mg twice daily oral long-acting morphine or placebo (as well as a blinded laxative) for 56 days in this trial conducted across 11 centers.
Using a numerical rating scale (NRS; 0 = not breathless at all; 10 = worst conceivable breathlessness), the main result was the worst breathlessness score for the previous 24 hours on day 28. Quality of life, morphine-related toxicities, physical activity levels, and worst cough NRS were secondary outcomes. The patients were eligible to be included in effectiveness and safety analyses if they received at least one dosage of the trial medication.
Only 3 individuals did not get the allotted therapy out of the 143 people who were randomly randomized to receive either morphine or a placebo (67 participants) between March 18, 2021, and October 26, 2023. The participants were primarily White (132 [94%]), male (93 [66%]), and their mean age was 70·5 (SD 9·4) years. By day 28, 66 (99%) of the morphine group and 64 (88%) of the placebo group achieved 90% or higher adherence.
With the exception of the better cough seen on day 56, researchers did not find any indication of a difference in the worst breathlessness at day 28 (morphine 6·19 [95% CI 5·57 to 6·81] vs placebo 6·10 [5·44 to 6·76]; adjusted mean difference 0·09 [95% CI –0·57 to 0·75], p=0·78]) or any secondary measure.
After multiple-measures adjustment, the increase in moderate to vigorous physical activity at day 28 (adjusted mean difference 9·51 min/day [0·54–18·48]) was not statistically significant.
Significant adverse events (15 vs. three, of which three in the morphine group and none in the placebo group were judged to be attributable to the study), study medication withdrawals (13 vs. two), and adverse events were more common in the morphine group (251 vs. 162). No one died as a result of therapy. Overall, the findings of this study states that there is no proof that morphine lessens the severity of the severe dyspnea.
Reference:
Johnson, M. J., Williams, B., Keerie, C., Tuck, S., Hart, S., Bajwah, S., Chaudhuri, N., Pearson, M., Cohen, J., Evans, R. A., Currow, D. C., Higginson, I. J., Hall, P., Atter, M., Norrie, J., Fallon, M. T., & MABEL collaborative. (2025). Morphine for chronic breathlessness (MABEL) in the UK: a multi-site, parallel-group, dose titration, double-blind, randomised, placebo-controlled trial. The Lancet. Respiratory Medicine. https://doi.org/10.1016/S2213-2600(25)00205-X
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