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

Currow, David; Watts, Gareth John; Johnson, Miriam (Miriam J.); McDonald, Christine F.; Miners, John O.; Somogyi, Andrew; Denehy, Linda; McCaffrey, Nicola; Eckert, Danny J.; McCloud, Philip; Louw, Sandra; Lam, Lawrence T.; Greene, Aine; Fazekas, Belinda; Clark, Katherine C.; Fong, Kwun; Agar, Meera; Joshi, Rohit; Kilbreath, Sharon; Ferreira, Diana H.; Ekström, Magnus

Hull York Medical School; Hull York Medical School
Chronic breathlessness
2017

Journal article


Rights
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
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.

Publisher
The University of Hull
Peer reviewed
Yes
Language
English
Extent
475 KB
Identifier
hull:15405

Journal

Journal title
BMJ Open
Publication date
2017
Publisher
BMJ Publishing Group
DOI
10.1136/ bmjopen-2017-018100
ISSN (Print)
2044-6055
ISSN (Electronic)
2044-6055
Volume
7
Issue
7
Notes

Copy of article first published in: BMJ Open, 2017, v.7, issue 7

Link
Published article
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