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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

Currow, David; Watts, Gareth John; Johnson, Miriam; McDonald, Christine F.; Miners, John O.; Somogyi, Andrew A; Denehy, Linda; McCaffrey, Nicola; Eckert, Danny J. and McCloud, Philip, et al. (2017) In BMJ Open 7(7).
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... (More)

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.

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published
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keywords
chronic breathlessness, opioids, palliative care, protocol, randomised control trial
in
BMJ Open
volume
7
issue
7
publisher
British Medical Journal Publishing Group
external identifiers
  • scopus:85025111360
ISSN
2044-6055
DOI
10.1136/bmjopen-2017-018100
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English
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yes
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aaa364a6-8c0b-4679-815f-818d0ac0d86b
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2017-08-29 14:29:45
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2017-08-30 03:00:02
@article{aaa364a6-8c0b-4679-815f-818d0ac0d86b,
  abstract     = {<p>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.</p>},
  articleno    = {e018100},
  author       = {Currow, David and Watts, Gareth John and Johnson, Miriam and McDonald, Christine F. and Miners, John O. and Somogyi, Andrew A and Denehy, Linda and McCaffrey, Nicola and Eckert, Danny J. and McCloud, Philip and Louw, Sandra and Lam, Lawrence and Greene, Aine and Fazekas, Belinda and Clark, Katherine C. and Fong, Kwun and Agar, Meera R. and Joshi, Rohit and Kilbreath, Sharon and Ferreira, Diana and Ekström, Magnus and , },
  issn         = {2044-6055},
  keyword      = {chronic breathlessness,opioids,palliative care,protocol,randomised control trial},
  language     = {eng},
  month        = {07},
  number       = {7},
  publisher    = {British Medical Journal Publishing Group},
  series       = {BMJ Open},
  title        = {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},
  url          = {http://dx.doi.org/10.1136/bmjopen-2017-018100},
  volume       = {7},
  year         = {2017},
}