Modified-release morphine or placebo for chronic breathlessness; the MABEL trial protocol

Kathryn Date; Bronwen Williams; Judith Cohen; Nazia Chaudhuri; Sabrina Bajwah; Mark Pearson; Irene J. Higginson; John Norrie; Catriona Keerie; Sharon Tuck; Peter S Hall; David C. Currow; Marie T Fallon; Miriam Johnson

doi:10.1183/23120541.00167-2023

Modified-release morphine or placebo for chronic breathlessness; the MABEL trial protocol

Kathryn Date, Bronwen Williams^*, Judith Cohen, Nazia Chaudhuri, Sabrina Bajwah, Mark Pearson, Irene J. Higginson, John Norrie, Catriona Keerie, Sharon Tuck, Peter S Hall, David C. Currow, Marie T Fallon, Miriam Johnson

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

Chronic breathlessness, a persistent and disabling symptom despite optimal treatment of underlying causes, is a frightening symptom with serious and widespread impact on patients and their carers. Clinical guidelines support the use of morphine for the relief of chronic breathlessness in common long-term conditions, but questions remain around clinical effectiveness, safety and longer-term (>7 days) administration. This trial will evaluate the effectiveness of low-dose oral modified release morphine in chronic breathlessness.

This is a multicentre, parallel group, double-blind, randomised, placebo-controlled trial. Participants [n=158] will be opioid-naïve with chronic breathlessness due to heart or lung disease, cancer or post-COVID-19. Participants will be randomised 1:1 to 5 mg oral modified-release morphine/placebo twice daily and docusate/placebo 100 mg twice daily for 56 days. Non-responders at Day 7 will dose escalate to 10 mg morphine/placebo twice daily at Day 15.

The primary endpoint (Day 28) measure will be worst breathlessness severity (past 24 h). Secondary outcome measures include worst cough, distress, pain; functional status; physical activity; quality of life; and early identification and management of morphine-related side effects. At Day 56, participants may opt to take open-label, oral modified-release morphine as part of usual care and complete quarterly breathlessness and toxicity questionnaires.

The study is powered to be able to reject the null hypothesis and an embedded normalisation process theory-informed qualitative sub-study will explore the adoption of morphine as a first-line pharmacological treatment for chronic breathlessness in clinical practice if effective.

Original language	English
Number of pages	15
Journal	ERJ Open Research
Volume	9
Issue number	4
Early online date	15 Jun 2023
DOIs	https://doi.org/10.1183/23120541.00167-2023
Publication status	E-pub ahead of print - 15 Jun 2023

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Date, K., Williams, B., Cohen, J., Chaudhuri, N., Bajwah, S., Pearson, M., Higginson, I. J., Norrie, J., Keerie, C., Tuck, S., Hall, P. S., Currow, D. C., Fallon, M. T., & Johnson, M. (2023). Modified-release morphine or placebo for chronic breathlessness; the MABEL trial protocol. ERJ Open Research, 9(4). Advance online publication. https://doi.org/10.1183/23120541.00167-2023

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title = "Modified-release morphine or placebo for chronic breathlessness; the MABEL trial protocol",

abstract = "Chronic breathlessness, a persistent and disabling symptom despite optimal treatment of underlying causes, is a frightening symptom with serious and widespread impact on patients and their carers. Clinical guidelines support the use of morphine for the relief of chronic breathlessness in common long-term conditions, but questions remain around clinical effectiveness, safety and longer-term (>7 days) administration. This trial will evaluate the effectiveness of low-dose oral modified release morphine in chronic breathlessness.This is a multicentre, parallel group, double-blind, randomised, placebo-controlled trial. Participants [n=158] will be opioid-na{\"i}ve with chronic breathlessness due to heart or lung disease, cancer or post-COVID-19. Participants will be randomised 1:1 to 5 mg oral modified-release morphine/placebo twice daily and docusate/placebo 100 mg twice daily for 56 days. Non-responders at Day 7 will dose escalate to 10 mg morphine/placebo twice daily at Day 15.The primary endpoint (Day 28) measure will be worst breathlessness severity (past 24 h). Secondary outcome measures include worst cough, distress, pain; functional status; physical activity; quality of life; and early identification and management of morphine-related side effects. At Day 56, participants may opt to take open-label, oral modified-release morphine as part of usual care and complete quarterly breathlessness and toxicity questionnaires.The study is powered to be able to reject the null hypothesis and an embedded normalisation process theory-informed qualitative sub-study will explore the adoption of morphine as a first-line pharmacological treatment for chronic breathlessness in clinical practice if effective.",

author = "Kathryn Date and Bronwen Williams and Judith Cohen and Nazia Chaudhuri and Sabrina Bajwah and Mark Pearson and Higginson, {Irene J.} and John Norrie and Catriona Keerie and Sharon Tuck and Hall, {Peter S} and Currow, {David C.} and Fallon, {Marie T} and Miriam Johnson",

note = "This paper presents independent research funded by the National Institute for Health Research (NIHR) for a commissioned call under the Health Technology Assessment programme (HTA Project: 17/34/01). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.",

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doi = "10.1183/23120541.00167-2023",

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AU - Date, Kathryn

AU - Williams, Bronwen

AU - Cohen, Judith

AU - Chaudhuri, Nazia

AU - Bajwah, Sabrina

AU - Pearson, Mark

AU - Higginson, Irene J.

AU - Norrie, John

AU - Keerie, Catriona

AU - Tuck, Sharon

AU - Hall, Peter S

AU - Currow, David C.

AU - Fallon, Marie T

AU - Johnson, Miriam

N1 - This paper presents independent research funded by the National Institute for Health Research (NIHR) for a commissioned call under the Health Technology Assessment programme (HTA Project: 17/34/01). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.

PY - 2023/6/15

Y1 - 2023/6/15

N2 - Chronic breathlessness, a persistent and disabling symptom despite optimal treatment of underlying causes, is a frightening symptom with serious and widespread impact on patients and their carers. Clinical guidelines support the use of morphine for the relief of chronic breathlessness in common long-term conditions, but questions remain around clinical effectiveness, safety and longer-term (>7 days) administration. This trial will evaluate the effectiveness of low-dose oral modified release morphine in chronic breathlessness.This is a multicentre, parallel group, double-blind, randomised, placebo-controlled trial. Participants [n=158] will be opioid-naïve with chronic breathlessness due to heart or lung disease, cancer or post-COVID-19. Participants will be randomised 1:1 to 5 mg oral modified-release morphine/placebo twice daily and docusate/placebo 100 mg twice daily for 56 days. Non-responders at Day 7 will dose escalate to 10 mg morphine/placebo twice daily at Day 15.The primary endpoint (Day 28) measure will be worst breathlessness severity (past 24 h). Secondary outcome measures include worst cough, distress, pain; functional status; physical activity; quality of life; and early identification and management of morphine-related side effects. At Day 56, participants may opt to take open-label, oral modified-release morphine as part of usual care and complete quarterly breathlessness and toxicity questionnaires.The study is powered to be able to reject the null hypothesis and an embedded normalisation process theory-informed qualitative sub-study will explore the adoption of morphine as a first-line pharmacological treatment for chronic breathlessness in clinical practice if effective.

AB - Chronic breathlessness, a persistent and disabling symptom despite optimal treatment of underlying causes, is a frightening symptom with serious and widespread impact on patients and their carers. Clinical guidelines support the use of morphine for the relief of chronic breathlessness in common long-term conditions, but questions remain around clinical effectiveness, safety and longer-term (>7 days) administration. This trial will evaluate the effectiveness of low-dose oral modified release morphine in chronic breathlessness.This is a multicentre, parallel group, double-blind, randomised, placebo-controlled trial. Participants [n=158] will be opioid-naïve with chronic breathlessness due to heart or lung disease, cancer or post-COVID-19. Participants will be randomised 1:1 to 5 mg oral modified-release morphine/placebo twice daily and docusate/placebo 100 mg twice daily for 56 days. Non-responders at Day 7 will dose escalate to 10 mg morphine/placebo twice daily at Day 15.The primary endpoint (Day 28) measure will be worst breathlessness severity (past 24 h). Secondary outcome measures include worst cough, distress, pain; functional status; physical activity; quality of life; and early identification and management of morphine-related side effects. At Day 56, participants may opt to take open-label, oral modified-release morphine as part of usual care and complete quarterly breathlessness and toxicity questionnaires.The study is powered to be able to reject the null hypothesis and an embedded normalisation process theory-informed qualitative sub-study will explore the adoption of morphine as a first-line pharmacological treatment for chronic breathlessness in clinical practice if effective.

U2 - 10.1183/23120541.00167-2023

DO - 10.1183/23120541.00167-2023

M3 - Article

SN - 2312-0541

VL - 9

JO - ERJ Open Research

JF - ERJ Open Research

IS - 4

ER -

Modified-release morphine or placebo for chronic breathlessness; the MABEL trial protocol

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