Clinical Trial

. 2017 Jul 17;7(7):e018100.

doi: 10.1136/bmjopen-2017-018100.

A pragmatic, phase III, multisite, double-blind, placebo-controlled, parallel-arm, dose increment randomised trial of regular, low-dose extended-release morphine for chronic breathlessness: Breathlessness, Exertion And Morphine Sulfate (BEAMS) study protocol

David Currow^{1

2}, Gareth John Watts³, Miriam Johnson^{2

4}, Christine F McDonald⁵, John O Miners⁶, Andrew A Somogyi⁷, Linda Denehy⁸, Nicola McCaffrey¹, Danny J Eckert⁹, Philip McCloud¹⁰, Sandra Louw¹⁰, Lawrence Lam¹¹, Aine Greene¹², Belinda Fazekas¹, Katherine C Clark^{3

13}, Kwun Fong¹⁴, Meera R Agar^{1

11

15

16}, Rohit Joshi¹⁷, Sharon Kilbreath¹¹, Diana Ferreira¹, Magnus Ekström^{1

18}; Australian national Palliative Care Clinical Studies Collaborative (PaCCSC)

Affiliations

¹ Discipline, Palliative and Supportive Services, Flinders University, Adelaide, Australia.
² Wolfson Palliative Care Research Centre, Hull York Medical School, University of Hull, Hull, UK.
³ Department of Palliative Care, Calvary Mater Newcastle, Newcastle, Australia.
⁴ Hull York Medical School, University of Hull, Hull, UK.
⁵ Department of Austin Health, Respiratory and Sleep Medicine, Austin Hospital, Heidelberg, Australia.
⁶ Clinical Pharmacology School of Medicine, Flinders University, Adelaide, Australia.
⁷ Department of Clinical Pharmacology, Adelaide Medical School, University of Adelaide, Adelaide, Australia.
⁸ School of Health Sciences, University of Melbourne, Parkville, Victoria, Australia.
⁹ Neuroscience Research Australia (NeRA) Randwick, New South Wales, Australia.
¹⁰ MCloud Consulting Group, Belrose, New South Wales, Australia.
¹¹ Faculty of Health, University of Technology Sydney, Sydney, Australia.
¹² Southern Adelaide Palliative Services, Adelaide, South Australia, Australia.
¹³ School of Medicine and Public Health, The University if Newcastle, Newcastle, New South Wales, Australia.
¹⁴ Thoracic Research Centre, The Prince Charles Hospital School of Medicine, University of Queensland, Australia.
¹⁵ Clinical Trials, Ingham Institute of Applied Medical Research, Sydney, Australia.
¹⁶ South West Sydney Clinical School, University of New South Wales, Sydney, Australia.
¹⁷ Department of Medical Oncology, University of Adelaide Lyell MEwin Hospital, Adelaide, Australia.
¹⁸ Department of Respiratory Medicine and Allergology, Institution for Clinical Sciences, Lund University, Sweden.

PMID: 28716797
PMCID: PMC5726102
DOI: 10.1136/bmjopen-2017-018100

Clinical Trial

A pragmatic, phase III, multisite, double-blind, placebo-controlled, parallel-arm, dose increment randomised trial of regular, low-dose extended-release morphine for chronic breathlessness: Breathlessness, Exertion And Morphine Sulfate (BEAMS) study protocol

David Currow et al. BMJ Open. 2017.

. 2017 Jul 17;7(7):e018100.

doi: 10.1136/bmjopen-2017-018100.

Authors

Affiliations

¹ Discipline, Palliative and Supportive Services, Flinders University, Adelaide, Australia.
² Wolfson Palliative Care Research Centre, Hull York Medical School, University of Hull, Hull, UK.
³ Department of Palliative Care, Calvary Mater Newcastle, Newcastle, Australia.
⁴ Hull York Medical School, University of Hull, Hull, UK.
⁵ Department of Austin Health, Respiratory and Sleep Medicine, Austin Hospital, Heidelberg, Australia.
⁶ Clinical Pharmacology School of Medicine, Flinders University, Adelaide, Australia.
⁷ Department of Clinical Pharmacology, Adelaide Medical School, University of Adelaide, Adelaide, Australia.
⁸ School of Health Sciences, University of Melbourne, Parkville, Victoria, Australia.
⁹ Neuroscience Research Australia (NeRA) Randwick, New South Wales, Australia.
¹⁰ MCloud Consulting Group, Belrose, New South Wales, Australia.
¹¹ Faculty of Health, University of Technology Sydney, Sydney, Australia.
¹² Southern Adelaide Palliative Services, Adelaide, South Australia, Australia.
¹³ School of Medicine and Public Health, The University if Newcastle, Newcastle, New South Wales, Australia.
¹⁴ Thoracic Research Centre, The Prince Charles Hospital School of Medicine, University of Queensland, Australia.
¹⁵ Clinical Trials, Ingham Institute of Applied Medical Research, Sydney, Australia.
¹⁶ South West Sydney Clinical School, University of New South Wales, Sydney, Australia.
¹⁷ Department of Medical Oncology, University of Adelaide Lyell MEwin Hospital, Adelaide, Australia.
¹⁸ Department of Respiratory Medicine and Allergology, Institution for Clinical Sciences, Lund University, Sweden.

PMID: 28716797
PMCID: PMC5726102
DOI: 10.1136/bmjopen-2017-018100

Abstract

Introduction: Chronic breathlessness is highly prevalent and distressing to patients and families. No medication is registered for its symptomatic reduction. The strongest evidence is for regular, low-dose, extended- release (ER) oral morphine. A recent large phase III study suggests the subgroup most likely to benefit have chronic obstructive pulmonary disease (COPD) and modified Medical Research Council breathlessness scores of 3 or 4. This protocol is for an adequately powered, parallel-arm, placebo-controlled, multisite, factorial, block-randomised study evaluating regular ER morphine for chronic breathlessness in people with COPD.

Methods and analysis: The primary question is what effect regular ER morphine has on worst breathlessness, measured daily on a 0-10 numerical rating scale. Uniquely, the coprimary outcome will use a FitBit to measure habitual physical activity. Secondary questions include safety and, whether upward titration after initial benefit delivers greater net symptom reduction. Substudies include longitudinal driving simulation, sleep, caregiver, health economic and pharmacogenetic studies. Seventeen centres will recruit 171 participants from respiratory and palliative care. The study has five phases including three randomisation phases to increasing doses of ER morphine. All participants will receive placebo or active laxatives as appropriate. Appropriate statistical analysis of primary and secondary outcomes will be used.

Ethics and dissemination: Ethics approval has been obtained. Results of the study will be submitted for publication in peer-reviewed journals, findings presented at relevant conferences and potentially used to inform registration of ER morphine for chronic breathlessness.

Trial registration number: NCT02720822; Pre-results.

Keywords: chronic breathlessness; opioids; palliative care; protocol; randomised control trial.

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Conflict of interest statement

Competing interests: DCC has received an unrestricted research grant from Mundipharma, is an unpaid member of an advisory board for Helsinn Pharmaceuticals and has consulted Mayne Pharma and received intellectual property payments from them. MJJ has received consulting payments from Mayne Pharma.

References

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A pragmatic, phase III, multisite, double-blind, placebo-controlled, parallel-arm, dose increment randomised trial of regular, low-dose extended-release morphine for chronic breathlessness: Breathlessness, Exertion And Morphine Sulfate (BEAMS) study protocol

Affiliations

A pragmatic, phase III, multisite, double-blind, placebo-controlled, parallel-arm, dose increment randomised trial of regular, low-dose extended-release morphine for chronic breathlessness: Breathlessness, Exertion And Morphine Sulfate (BEAMS) study protocol

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Substances

Associated data

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical