Oral modified release morphine for breathlessness in chronic heart failure: a randomized placebo‐controlled trial

Authors

• Miriam J. Johnson, University of Hull
• Sarah Cockayne, University of York
• David C. Currow, University of Hull
• Kerry Bell, University of York
• Kate Hicks, University of York
• Caroline Fairhurst, University of York
• Rhian Gabe, University of York
• David Torgerson, University of York
• Laura Jefferson, University of York
• Stephen Oxberry, Calderdale and Huddersfield NHS Foundation Trust
• Justin Ghosh, York Teaching Hospital NHS Foundation Trust
• Karen J. Hogg, University of Glasgow
• Jeremy Murphy, County Durham and Darlington NHS Foundation Trust
• Victoria Allgar, Peninsula Medical School
• John G.F. Cleland, University of Glasgow
• Andrew L. Clark, Hull University Teaching Hospitals NHS Trust

ORCID

• Victoria Allgar: 0000-0002-5228-2623

Abstract

AbstractAimsMorphine is shown to relieve chronic breathlessness in chronic obstructive pulmonary disease. There are no definitive data in people with heart failure. We aimed to determine the effectiveness and cost‐effectiveness of 12 weeks morphine therapy for the relief of chronic breathlessness in people with chronic heart failure compared with placebo.Methods and resultsParallel group, double‐blind, randomized, placebo‐controlled, phase III trial of 20 mg daily oral modified release morphine was conducted in 13 sites in England and Scotland: hospital/community cardiology or palliative care outpatients. The primary analysis compared between‐group numerical rating scale average breathlessness/24 hours at week 4 using a covariance pattern linear mixed model. Secondary outcomes included treatment‐emergent harms (worse or new). The trial closed early due to slow recruitment, randomizing 45 participants [average age 72 (range 39–89) years; 84% men; 98% New York Heart Association class III]. For the primary analysis, the adjusted mean difference was 0.26 (95% confidence interval, −0.86 to 1.37) in favour of placebo. All other breathlessness measures improved in both groups (week 4 change‐from‐baseline) but by more in those assigned to morphine. Neither group was excessively drowsy at baseline or week 4. There were no between‐group differences in quality of life (Kansas) or cognition (Montreal) at any time point. There was no exercise‐related desaturation and no change between baseline and week 4 in either group. There was no change in vital signs at week 4. The natriuretic peptide measures fell in both groups but by more in the morphine group [morphine 2169 (1092, 3851) pg/mL vs. placebo 2851 (1694, 5437)] pg/mL. There was no excess serious adverse events in the morphine group. Treatment‐emergent harms during the first week were more common in the morphine group; all apart from 1 were ≤ grade 2.ConclusionsWe could not answer our primary objectives due to inadequate power. However, we provide novel placebo‐controlled medium‐term benefit and safety data useful for clinical practice and future trial design. Morphine should only be prescribed in this population when other measures are unhelpful and with early management of side effects.

DOI Link

10.1002/ehf2.12498

Publication Date

2019-01-01

Publication Title

ESC heart failure

Volume

6

Issue

6

Embargo Period

9999-12-31

First Page

1149

Last Page

1160

Recommended Citation

Johnson, M., Cockayne, S., Currow, D., Bell, K., Hicks, K., Fairhurst, C., Gabe, R., Torgerson, D., Jefferson, L., Oxberry, S., Ghosh, J., Hogg, K., Murphy, J., Allgar, V., Cleland, J., & Clark, A. (2019) 'Oral modified release morphine for breathlessness in chronic heart failure: a randomized placebo‐controlled trial', ESC heart failure, 6(6), pp. 1149-1160. Available at: 10.1002/ehf2.12498