title: A randomized controlled trial on the benefits and respiratory adverse effects of morphine for refractory dyspnea in patients with COPD: Protocol of the MORDYC study.
abstract: Dyspnea is one of the most reported symptoms of patients with advanced Chronic Obstructive Pulmonary Disease (COPD) and is often undertreated. Morphine has proven to be an effective treatment for dyspnea and is recommended in clinical practice guidelines, but questions concerning benefits and respiratory adverse effects remain. This study primarily evaluates the impact of oral sustained release morphine (morphine SR) on health-related quality of life and respiratory adverse effects in patients with COPD. Secondary objectives include the impact on exercise capacity, the relationship between description and severity of dyspnea and the presence of a clinically relevant response to morphine, and cost-effectiveness. A single-center, randomized, double blind, placebo controlled intervention study will be performed in 124 patients with COPD who recently completed a comprehensive pulmonary rehabilitation program. Participants will receive 20-30 mg/24h morphine SR or placebo for four weeks. After the intervention, participants will be followed for twelve weeks. Outcomes include: the COPD Assessment Test, six minute walking test, Multidimensional Dyspnea Scale and a cost diary. Furthermore, lung function and arterial blood gasses will be measured. These measures will be assessed during a baseline and outcome assessment, two home visits, two phone calls, and three follow-up assessments. The intervention and control group will be compared using uni- and multivariate regression analysis and logistic regression analysis. Finally, an economic evaluation will be performed from a societal and healthcare perspective. The current manuscript describes the rationale and methods of this study and provides an outline of the possible strengths, weaknesses and clinical consequences.
authors.affiliation: Department of Health Services Research, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. Electronic address: c.vandenberg@maastrichtuniversity.nl.
authors.forename: C A
authors.initials: CA
authors.lastname: Verberkt
authors.affiliation: Centre of Expertise for Palliative Care, Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.
authors.forename: M H J
authors.initials: MH
authors.lastname: van den Beuken-van Everdingen
authors.affiliation: CIRO, Centre of Expertise for Chronic Organ Failure, Horn, The Netherlands.
authors.forename: F M E
authors.initials: FM
authors.lastname: Franssen
authors.affiliation: Department of Clinical Epidemiology and Medical Technology Assessment, CAPHRI School for Public Health and Primary Care, Faculty of Health, Medicine and Life Sciences, Maastricht University,Maastricht, The Netherlands.
authors.forename: C D
authors.initials: CD
authors.lastname: Dirksen
authors.affiliation: Department of Health Services Research, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands; Department of Family Medicine, Maastricht University, Maastricht, The Netherlands.
authors.forename: J M G A
authors.initials: JM
authors.lastname: Schols
authors.affiliation: CIRO, Centre of Expertise for Chronic Organ Failure, Horn, The Netherlands; Department of Respiratory Medicine, Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands.
authors.forename: E F M
authors.initials: EF
authors.lastname: Wouters
authors.affiliation: Centre of Expertise for Palliative Care, Maastricht University Medical Centre (MUMC+), Maastricht, The Netherlands; CIRO, Centre of Expertise for Chronic Organ Failure, Horn, The Netherlands.
authors.forename: D J A
authors.initials: DJ
authors.lastname: Janssen
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000627:therapeutic use*; D002985:Clinical Protocols; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004417:Dyspnea / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications*; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D009020:Morphine
keywords: Adverse effects; Chronic Obstructive Pulmonary Disease; Clinical effectiveness; Dyspnea; Morphine; Research protocol