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

Cicely Saunders Institute of Palliative Care, Policy & Rehabilitation

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

4 Citations (Scopus)

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.

Original language	English
Journal	ERJ Open Research
Volume	9
Issue number	4
Early online date	14 Jul 2023
DOIs	https://doi.org/10.1183/23120541.00167-2023
Publication status	E-pub ahead of print - 14 Jul 2023

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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.",

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",

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T2 - the MABEL trial protocol

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

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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.

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

Abstract

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