Effect of Regular, Low-Dose, Extended-release Morphine on Chronic Breathlessness in Chronic Obstructive Pulmonary Disease: The BEAMS Randomized Clinical Trial

Key PointsQuestionDoes regular, low-dose, extended-release morphine improve the intensity of worst breathlessness in people with chronic obstructive pulmonary disease (COPD) and severe chronic breathlessness? FindingsIn this randomized clinical trial including 156 people with COPD and chronic breathlessness, treatment with 8 mg/d and 16 mg/d of oral extended-release morphine for 1 week resulted in a mean difference of -0.3 and -0.3, respectively, for change in the intensity of worst breathlessness compared with placebo; neither difference was statistically significant. The scores range from 0 to 10 (a score of 10 being the worst or most intense) on the numerical rating scale that was used. MeaningExtended-release morphine compared with placebo did not significantly reduce the intensity of worst breathlessness in people with COPD. 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, -47699 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 This randomized clinical trial compares the effect of different doses (8 mg/d or 16 mg/d) of extended-release morphine vs placebo on chronic breathlessness in people with chronic obstructive pulmonary disease (COPD).

Automated summary

This randomized clinical trial compared the effect of different doses (8 mg/d or 16 mg/d) of extended-release morphine versus placebo on chronic breathlessness in people with chronic obstructive pulmonary disease (COPD). The study found that 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.