Effect of Regular, Low-Dose, Extended-release Morphine on Chronic Breathlessness in Chronic Obstructive Pulmonary Disease
Author:
Ekström Magnus12, Ferreira Diana3, Chang Sungwon2, Louw Sandra4, Johnson Miriam J.5, Eckert Danny J.6, Fazekas Belinda2, Clark Katherine J.78, Agar Meera R.2, Currow David C.39, McDonald Christine10, Miners John10, Kirkpatrick Carl10, Somogyi Andrew10, Denehy Linda10, McCaffrey Nikki10, Lam Lawrence10, Greene Aine10, Le Brian10, Clark Katherine10, Fong Kwun10, Agar Meera10, Joshi Rohit10, Kilbreath Sharon10, Ferreira Diana10, Clow Angela10, Smith Nina10, Ryan Richella10, Booth Sara10, Martin Peter10, Kanathigoda Suharsha10, Sheehan Caitlin10, Lee Jessica10, Allcroft Peter10, Cameron-Taylor Erica10, Good Philip10, Welch Louise10, Chye Richard10, Phillip Jennifer10, Wheatley John10, krishnan Anu10, Epton Michael10, Aggarwal Rajesh10, McCloud Philip10, Chan Jessie10, Bellamy Douglas10, Bellemore Frances10, Bhatarai Priyanka10, Biggins Helen10, Birch Mary-Rose10, Burke Lesley10, Burns Tracey10, Byfieldt Naomi10, Charlesworth Diana10, Collins Gillian10, Cooper Helen10, Cosic Urska10, Courtney Deborah10, Cupples Georgie10, Dowd Anna10, Dunleavey Ruth10, Edgar Terence10, Fischer Amanda10, Fuhrmeister Lisa10, Gesling Jan10, Hart Rosetta10, Hopkinson Kim10, Kaczurowski Michelle10, Kidd Sally10, Kingi Ngaire10, Margitanovic Vera10, McCarthy Gillian10, O'Reilly Robin10, Perry Mary10, Raymond Bronwyn10, Saward Di10, Shanon-Honson Aaron10, Sullivan Karyn10, Tonkin Michelle10, Vandersman Zac10, West Penny10, Wilcock Julie10, Storer Malina10, Nestor Sarah10, Thristiawati Safrina10, Sidhu Manraaj10,
Affiliation:
1. Faculty of Medicine, Department of Clinical Sciences, Respiratory Medicine, Allergology, and Palliative Medicine, Lund University, Lund, Sweden 2. Faculty of Health Improving Palliative, Aged, and Chronic Care Through Clinical Research and Translation, University of Technology Sydney, Ultimo, Australia 3. Faculty of Science, Medicine, and Health, University of Wollongong, Wollongong, Australia 4. McCloud Consulting Group, Belrose, Australia 5. Wolfson Palliative Care Research Centre, Hull York Medical School, University of Hull, Hull, England 6. Adelaide Institute for Sleep Health, Flinders University, Adelaide, Australia 7. Palliative Care Network, Northern Sydney Local Health District, Sydney, Australia 8. Northern Clinical School, University of Sydney, Sydney, Australia 9. Palliative and Supportive Services, Flinders University, Adelaide, Australia 10. for the Australian National Palliative Care Clinical Studies Collaborative
Abstract
ImportanceChronic breathlessness is common in people with chronic obstructive pulmonary disease (COPD). Regular, low-dose, extended-release morphine may relieve breathlessness, but evidence about its efficacy and dosing is needed.ObjectiveTo determine the effect of different doses of extended-release morphine on worst breathlessness in people with COPD after 1 week of treatment.Design, Setting, and ParticipantsMulticenter, double-blind, placebo-controlled randomized clinical trial including people with COPD and chronic breathlessness (defined as a modified Medical Research Council score of 3 to 4) conducted at 20 centers in Australia. People were enrolled between September 1, 2016, and November 20, 2019, and followed up through December 26, 2019.InterventionsPeople were randomized 1:1:1 to 8 mg/d or 16 mg/d of oral extended-release morphine or placebo during week 1. At the start of weeks 2 and 3, people were randomized 1:1 to 8 mg/d of extended-release morphine, which was added to the prior week’s dose, or placebo.Main Outcomes and MeasuresThe primary outcome was change in the intensity of worst breathlessness on a numerical rating scale (score range, 0 [none] to 10 [being worst or most intense]) using the mean score at baseline (from days −3 to −1) to the mean score after week 1 of treatment (from days 5 to 7) in the 8 mg/d and 16 mg/d of extended-release morphine groups vs the placebo group. Secondary outcomes included change in daily step count measured using an actigraphy device from baseline (day −1) to the mean step count from week 3 (from days 19 to 21).ResultsAmong the 160 people randomized, 156 were included in the primary analyses (median age, 72 years [IQR, 67 to 78 years]; 48% were women) and 138 (88%) completed treatment at week 1 (48 in the 8 mg/d of morphine group, 43 in the 16 mg/d of morphine group, and 47 in the placebo group). The change in the intensity of worst breathlessness at week 1 was not significantly different between the 8 mg/d of morphine group and the placebo group (mean difference, −0.3 [95% CI, −0.9 to 0.4]) or between the 16 mg/d of morphine group and the placebo group (mean difference, −0.3 [95%, CI, −1.0 to 0.4]). At week 3, the secondary outcome of change in mean daily step count was not significantly different between the 8 mg/d of morphine group and the placebo group (mean difference, −1453 [95% CI, −3310 to 405]), between the 16 mg/d of morphine group and the placebo group (mean difference, −1312 [95% CI, −3220 to 596]), between the 24 mg/d of morphine group and the placebo group (mean difference, −692 [95% CI, −2553 to 1170]), or between the 32 mg/d of morphine group and the placebo group (mean difference, −1924 [95% CI, −47 699 to 921]).Conclusions and RelevanceAmong people with COPD and severe chronic breathlessness, daily low-dose, extended-release morphine did not significantly reduce the intensity of worst breathlessness after 1 week of treatment. These findings do not support the use of these doses of extended-release morphine to relieve breathlessness.Trial RegistrationClinicalTrials.gov Identifier: NCT02720822
Publisher
American Medical Association (AMA)
Cited by
36 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献
|
|