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.

2017-07-17

Currow, David

Watts, Gareth John

Johnson, Miriam

McDonald, Christine F

Miners, John O

Somogyi, Andrew A

Denehy, Linda

McCaffrey, Nicola

Eckert, Danny J

McCloud, Philip

Louw, Sandra

Lam, Lawrence

Greene, Aine

Fazekas, Belinda

Clark, Katherine C

Fong, Kwun

Agar, Meera R

Joshi, Rohit

Kilbreath, Sharon

Ferreira, Diana

Ekström, Magnus

chronic breathlessness

opioids

palliative care

protocol

randomised control trial

Journal Article

0000-0003-1988-1250

0000-0001-6481-3391

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10.1136/bmjopen-2017-018100

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. 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 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. NCT02720822; Pre-results.

link

BMJ Open 2017; 7(7): e018100

BMJ Open