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 Higginson; John Norrie; Catriona Keerie; Sharon Tuck; Peter Hall; David Currow; Marie 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 Higginson
, John Norrie
, Catriona Keerie
, Sharon Tuck
, Peter Hall
, David Currow
, Marie Fallon
, Miriam Johnson

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

7 Citations (Scopus)

47 Downloads (Pure)

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-naïve with chronic breathlessness due to heart or lung disease, cancer or post-coronavirus disease 2019. 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 end-point (Day 28) measure will be worst breathlessness severity (previous 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 substudy will explore the adoption of morphine as a first-line pharmacological treatment for chronic breathlessness in clinical practice if effective. [Abstract copyright: Copyright ©The authors 2023.]

Original language	English
Article number	00167-2023
Pages (from-to)	1-16
Number of pages	16
Journal	ERJ Open Research
Volume	9
Issue number	4
Early online date	14 Aug 2023
DOIs	https://doi.org/10.1183/23120541.00167-2023
Publication status	Published online - 14 Aug 2023

Bibliographical note

Funding Information:
Support statement: 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. Funding information for this article has been deposited with the Crossref Funder Registry.

Funding Information:
We wish to acknowledge the contributions of the sponsor (Hull University Teaching Hospitals NHS Trust) and participating sites that have contributed to study recruitment: University Hospitals Birmingham NHS Foundation Trust, North Bristol NHS Trust, Fife Health Board, Greater Glasgow Health Board, Hull University Teaching Hospitals NHS Trust, Leeds Teaching Hospitals NHS Trust, University Hospitals of Leicester NHS Trust, Lothian Health Board, Manchester University NHS Foundation Trust and University Hospitals Plymouth NHS Trust. We would also like to thank the members of the Trial Management Group, Trial Steering Group, and Data Monitoring and Ethics Committee for their ongoing support. Finally, we would like to express our thanks and gratitude to all participants and carers that took the time to participate in this study. This study is registered at EudraCT with identifier number 2019-002479-33. It is intended that individual participant data that underlie the results reported in final results papers will be made available for sharing for research purposes after de-identification. Data will not be shared until after completion of the final study report to the funder but will then be available with no end date. Final anonymised clinical trial datasets and metadata will be produced in accordance with participant consent, and stored in an appropriate format to enable discoverability and sharing in the University of Hull’s data repository HYDRA. Publications will include data availability statements.

Publisher Copyright:
© The authors 2023.

Funding

Funding Information: Support statement: 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. Funding information for this article has been deposited with the Crossref Funder Registry. Funding Information: We wish to acknowledge the contributions of the sponsor (Hull University Teaching Hospitals NHS Trust) and participating sites that have contributed to study recruitment: University Hospitals Birmingham NHS Foundation Trust, North Bristol NHS Trust, Fife Health Board, Greater Glasgow Health Board, Hull University Teaching Hospitals NHS Trust, Leeds Teaching Hospitals NHS Trust, University Hospitals of Leicester NHS Trust, Lothian Health Board, Manchester University NHS Foundation Trust and University Hospitals Plymouth NHS Trust. We would also like to thank the members of the Trial Management Group, Trial Steering Group, and Data Monitoring and Ethics Committee for their ongoing support. Finally, we would like to express our thanks and gratitude to all participants and carers that took the time to participate in this study. This study is registered at EudraCT with identifier number 2019-002479-33. It is intended that individual participant data that underlie the results reported in final results papers will be made available for sharing for research purposes after de-identification. Data will not be shared until after completion of the final study report to the funder but will then be available with no end date. Final anonymised clinical trial datasets and metadata will be produced in accordance with participant consent, and stored in an appropriate format to enable discoverability and sharing in the University of Hull’s data repository HYDRA. Publications will include data availability statements. Publisher Copyright: © The authors 2023.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1183/23120541.00167-2023

23120541.00167-2023.fullFinal published version, 501 KBLicence: CC BY-NC

Cite this

Date, K., Williams, B., Cohen, J., Chaudhuri, N., Bajwah, S., Pearson, M., Higginson, I., Norrie, J., Keerie, C., Tuck, S., Hall, P., Currow, D., Fallon, M., & Johnson, M. (2023). Modified-release morphine or placebo for chronic breathlessness: the MABEL trial protocol. ERJ Open Research, 9(4), 1-16. Article 00167-2023. 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-coronavirus disease 2019. 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 end-point (Day 28) measure will be worst breathlessness severity (previous 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 substudy will explore the adoption of morphine as a first-line pharmacological treatment for chronic breathlessness in clinical practice if effective. [Abstract copyright: Copyright {\textcopyright}The authors 2023.]",

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

note = "Funding Information: Support statement: 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. Funding information for this article has been deposited with the Crossref Funder Registry. Funding Information: We wish to acknowledge the contributions of the sponsor (Hull University Teaching Hospitals NHS Trust) and participating sites that have contributed to study recruitment: University Hospitals Birmingham NHS Foundation Trust, North Bristol NHS Trust, Fife Health Board, Greater Glasgow Health Board, Hull University Teaching Hospitals NHS Trust, Leeds Teaching Hospitals NHS Trust, University Hospitals of Leicester NHS Trust, Lothian Health Board, Manchester University NHS Foundation Trust and University Hospitals Plymouth NHS Trust. We would also like to thank the members of the Trial Management Group, Trial Steering Group, and Data Monitoring and Ethics Committee for their ongoing support. Finally, we would like to express our thanks and gratitude to all participants and carers that took the time to participate in this study. This study is registered at EudraCT with identifier number 2019-002479-33. It is intended that individual participant data that underlie the results reported in final results papers will be made available for sharing for research purposes after de-identification. Data will not be shared until after completion of the final study report to the funder but will then be available with no end date. Final anonymised clinical trial datasets and metadata will be produced in accordance with participant consent, and stored in an appropriate format to enable discoverability and sharing in the University of Hull{\textquoteright}s data repository HYDRA. Publications will include data availability statements. Publisher Copyright: {\textcopyright} The authors 2023.",

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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

AU - Norrie, John

AU - Keerie, Catriona

AU - Tuck, Sharon

AU - Hall, Peter

AU - Currow, David

AU - Fallon, Marie

AU - Johnson, Miriam

N1 - Funding Information: Support statement: 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. Funding information for this article has been deposited with the Crossref Funder Registry. Funding Information: We wish to acknowledge the contributions of the sponsor (Hull University Teaching Hospitals NHS Trust) and participating sites that have contributed to study recruitment: University Hospitals Birmingham NHS Foundation Trust, North Bristol NHS Trust, Fife Health Board, Greater Glasgow Health Board, Hull University Teaching Hospitals NHS Trust, Leeds Teaching Hospitals NHS Trust, University Hospitals of Leicester NHS Trust, Lothian Health Board, Manchester University NHS Foundation Trust and University Hospitals Plymouth NHS Trust. We would also like to thank the members of the Trial Management Group, Trial Steering Group, and Data Monitoring and Ethics Committee for their ongoing support. Finally, we would like to express our thanks and gratitude to all participants and carers that took the time to participate in this study. This study is registered at EudraCT with identifier number 2019-002479-33. It is intended that individual participant data that underlie the results reported in final results papers will be made available for sharing for research purposes after de-identification. Data will not be shared until after completion of the final study report to the funder but will then be available with no end date. Final anonymised clinical trial datasets and metadata will be produced in accordance with participant consent, and stored in an appropriate format to enable discoverability and sharing in the University of Hull’s data repository HYDRA. Publications will include data availability statements. Publisher Copyright: © The authors 2023.

PY - 2023/8/14

Y1 - 2023/8/14

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-coronavirus disease 2019. 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 end-point (Day 28) measure will be worst breathlessness severity (previous 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 substudy will explore the adoption of morphine as a first-line pharmacological treatment for chronic breathlessness in clinical practice if effective. [Abstract copyright: Copyright ©The authors 2023.]

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-coronavirus disease 2019. 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 end-point (Day 28) measure will be worst breathlessness severity (previous 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 substudy will explore the adoption of morphine as a first-line pharmacological treatment for chronic breathlessness in clinical practice if effective. [Abstract copyright: Copyright ©The authors 2023.]

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ER -

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

Abstract

Bibliographical note

Funding

UN SDGs

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