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

Johnson, Miriam J.; Cockayne, Sarah; Currow, David C.; Bell, Kerry; Hicks, Kate; Fairhurst, Caroline; Gabe, Rhian; Torgerson, David; Jefferson, Laura; Oxberry, Stephen; Ghosh, Justin; Hogg, Karen; Murphy, Jeremy; Allgar, Victoria; Cleland, John; Clark, Andrew

Authors

Sarah Cockayne

David C. Currow

Kerry Bell

Kate Hicks

Caroline Fairhurst

Rhian Gabe

David Torgerson

Laura Jefferson

Stephen Oxberry

Justin Ghosh

Karen Hogg

Jeremy Murphy

Victoria Allgar

John Cleland

Andrew Clark



Abstract

© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology. Aims: Morphine 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 results: Parallel 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. Conclusions: We 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.

Citation

Hogg, K. J., Cleland, J. G., Clark, A. L., Johnson, M. J., Cockayne, S., Currow, D. C., …Clark, A. (2019). Oral modified release morphine for breathlessness in chronic heart failure: a randomized placebo-controlled trial. ESC Heart Failure, 6(6), 1149-1160. https://doi.org/10.1002/ehf2.12498

Journal Article Type Article
Acceptance Date Jun 18, 2019
Online Publication Date Aug 6, 2019
Publication Date Dec 1, 2019
Deposit Date Jun 27, 2019
Publicly Available Date Sep 10, 2019
Journal ESC Heart Failure
Electronic ISSN 2055-5822
Publisher Wiley Open Access
Peer Reviewed Peer Reviewed
Volume 6
Issue 6
Pages 1149-1160
DOI https://doi.org/10.1002/ehf2.12498
Keywords Heart failure; Randomized controlled trial; Morphine; Breathlessness; Dyspnea
Public URL https://hull-repository.worktribe.com/output/2047965
Publisher URL https://onlinelibrary.wiley.com/doi/full/10.1002/ehf2.12498
Related Public URLs http://eprints.whiterose.ac.uk/147608/

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Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/

Copyright Statement
©2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology. ESC HEART FAILURE ESC Heart Failure(2019)Published online in Wiley Online Library (wileyonlinelibrary.com) DOI:10.1002/ehf2.12498 This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.





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