| 1. |
- Ekström, Magnus, et al.
(författare)
-
Effect of Regular, Low-Dose, Extended-release Morphine on Chronic Breathlessness in Chronic Obstructive Pulmonary Disease : The BEAMS Randomized Clinical Trial
- 2022
-
Ingår i: JAMA. - : American Medical Association (AMA). - 0098-7484. ; 328:20, s. 2022-2032
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Chronic 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.OBJECTIVE: To 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 PARTICIPANTS: Multicenter, 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.INTERVENTIONS: People 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 MEASURES: The 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).RESULTS: Among 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 RELEVANCE: Among 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 REGISTRATION: ClinicalTrials.gov Identifier: NCT02720822.
|
|
| 2. |
- Currow, David, et al.
(författare)
-
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
-
Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 7:7
-
Tidskriftsartikel (refereegranskat)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. Trial registration number NCT02720822; Pre-results.
|
|
| 3. |
- Currow, David C., et al.
(författare)
-
Chronic breathlessness and sleep problems : A population-based survey
- 2021
-
Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 11:8
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives This study aimed to explore the relationship (presence and severity) between chronic breathlessness and sleep problems, independently of diagnoses and health service contact by surveying a large, representative sample of the general population. Setting Analysis of the 2017 South Australian Health Omnibus Survey, an annual, cross-sectional, face-to-face, multistage, clustered area systematic sampling survey carried out in Spring 2017. Chronic breathlessness was self-reported using the ordinal modified Medical Research Council (mMRC; scores 0 (none) to 4 (housebound)) where breathlessness has been present for more than 3 of the previous 6 months. a € Sleep problems - ever' and a € sleep problem - current' were assessed dichotomously. Regression models were adjusted for age; sex and body mass index (BMI). Results 2900 responses were available (mean age 48.2 years (SD=18.6); 51% were female; mean BMI 27. 1 (SD=5.9)). Prevalence was: 2.7% (n=78) sleep problems - past; 6.8% (n=198) sleep problems - current and breathlessness (mMRC 1-4) was 8.8% (n=254). Respondents with sleep problemspast were more likely to be breathless, older with a higher BMI and sleep problems - present also included a higher likelihood of being female. After adjusting for age, sex and BMI, respondents with chronic breathlessness had 1.9 (95% CI=1.0 to 3.5) times the odds of sleep problems - past and sleep problems - current (adjusted OR=2.3; 95% CI=1.6 to 3.3). Conclusions There is a strong association between the two prevalent conditions. Future work will seek to understand if there is a causal relationship using validated sleep assessment tools and whether better managing one condition improves the other.
|
|
| 4. |
- Ferreira, Diana H., et al.
(författare)
-
Extended-Release Morphine for Chronic Breathlessness in Pulmonary Arterial Hypertension—A Randomized, Double-Blind, Placebo-Controlled, Crossover Study
- 2018
-
Ingår i: Journal of Pain and Symptom Management. - : Elsevier BV. - 0885-3924. ; 56:4, s. 483-492
-
Tidskriftsartikel (refereegranskat)abstract
- Context: Pulmonary arterial hypertension (PAH) affects people of all ages and is associated with poor prognosis. Chronic breathlessness affects almost all people with PAH. Objectives: This randomized, placebo-controlled, double-blind, crossover study aimed to evaluate the effects of regular, low-dose, extended-release (ER) morphine for PAH-associated chronic breathlessness. Methods: Participants with PAH-associated chronic breathlessness were randomized to 1) seven days of ER morphine 20 mg, 2) seven-day washout, and 3) seven days of identically looking placebo, or vice versa. Primary end points were breathlessness “right now”—morning and evening—measured with a Visual Analogue Scale. Secondary end points included additional breathlessness measures, quality of life, function, harms, and blinded treatment preference (ACTRN12609000209291). Results: Within a period of seven years, 50 patients were assessed in detail and 23 (46%) were randomized (despite broad eligibility criteria). Four participants withdrew while taking morphine. Nineteen participants completed the study. Breathlessness “right now” was higher on morphine compared with placebo both for morning [mean (M) ± SD 31.7 ± 25 mm vs. 26.9 ± 22 mm; effect size (80% CI) = −0.22 (−0.6 to 0.2)] and evening [(M ± SD 33.5 ± 28 mm vs. 25.6 ± 21 mm; effect size (80% CI) = −0.33 (−0.8 to 0.1)]. All secondary measures of breathlessness were higher with morphine as were nausea and constipation. Conclusion: This study does not support a Phase III study of ER morphine for people with PAH-associated chronic breathlessness. Recruiting to the target sample size was difficult, the direction of effect in every measure of breathlessness favored placebo and morphine generated more harms.
|
|
