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

Johnson, MJ; Cockayne, S; Currow, DC; Bell, K; Hicks, K; Fairhurst, C; Gabe, R; Torgerson, D; Jefferson, L; Oxberry, S; Ghosh, J; Hogg, KJ; Murphy, J; Allgar, V; Cleland, JGF; Clark, AL

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

Johnson, MJ Cockayne, S Currow, DC

Bell, K Hicks, K Fairhurst, C Gabe, R Torgerson, D Jefferson, L Oxberry, S Ghosh, J Hogg, KJ Murphy, J Allgar, V Cleland, JGF Clark, AL

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Publication Type:: Journal Article
Citation:: ESC Heart Failure, 2019, 6 (6), pp. 1149 - 1160
Issue Date:: 2019-12-01

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Field	Value	Language
dc.contributor.author	Johnson, MJ	en_US
dc.contributor.author	Cockayne, S	en_US
dc.contributor.author	Currow, DC https://orcid.org/0000-0003-1988-1250	en_US
dc.contributor.author	Bell, K	en_US
dc.contributor.author	Hicks, K	en_US
dc.contributor.author	Fairhurst, C	en_US
dc.contributor.author	Gabe, R	en_US
dc.contributor.author	Torgerson, D	en_US
dc.contributor.author	Jefferson, L	en_US
dc.contributor.author	Oxberry, S	en_US
dc.contributor.author	Ghosh, J	en_US
dc.contributor.author	Hogg, KJ	en_US
dc.contributor.author	Murphy, J	en_US
dc.contributor.author	Allgar, V	en_US
dc.contributor.author	Cleland, JGF	en_US
dc.contributor.author	Clark, AL	en_US
dc.date.available	2019-06-18	en_US
dc.date.issued	2019-12-01	en_US
dc.identifier.citation	ESC Heart Failure, 2019, 6 (6), pp. 1149 - 1160	en_US
dc.identifier.uri	http://hdl.handle.net/10453/139037
dc.description.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.	en_US
dc.relation.ispartof	ESC Heart Failure	en_US
dc.relation.isbasedon	10.1002/ehf2.12498	en_US
dc.rights	info:eu-repo/semantics/openAccess
dc.title	Oral modified release morphine for breathlessness in chronic heart failure: a randomized placebo-controlled trial	en_US
dc.type	Journal Article
utslib.citation.volume	6	en_US
utslib.for	1102 Cardiorespiratory Medicine and Haematology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
pubs.organisational-group	/University of Technology Sydney/Faculty of Health/IMPACCT
utslib.copyright.status	open_access	*
pubs.issue	6	en_US
pubs.publication-status	Published	en_US
pubs.volume	6	en_US

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.

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http://hdl.handle.net/10453/139037