Morphine for Palliative Treatment of Refractory Dyspnea in Patients With Advanced COPD: Benefits and Respiratory Adverse Effects
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 124
- 试验地点
- 1
- 主要终点
- Disease-specific health-related quality of life (COPD Assessment Test (CAT))
研究概览
简要总结
Dyspnea is the most reported symptom of patients with advanced Chronic Obstructive Pulmonary Disease (COPD) and is undertreated. Morphine is an effective treatment for dyspnea and is recommended in clinical practice guidelines, but questions concerning benefits and concerns about respiratory adverse effects remain. For example, the effect on health-related quality of life and functional capacity is unknown. In one-third of the patients oral sustained release morphine (morphine SR) doesn't relieve dyspnea and it remains unknown whether severity and descriptors of breathlessness may predict a response to morphine. Finally, cost-effectiveness of morphine SR in this patient group is unknown. Therefore, prescription of morphine to patients with COPD is limited.
Objectives of this double blind randomized controlled trial are to study the effect of oral administration of morphine SR on health-related quality of life, respiratory adverse effects, and functional capacity; to explore whether description and severity of breathlessness are related with a clinically relevant response to morphine and to analyse the cost-effectiveness of morphine SR. The study population will consist of 124 clinically stable outpatients with COPD and severe dyspnea despite optimal pharmacological and non-pharmacological treatment.
详细描述
Participants will be outpatients with a confirmed diagnosis of COPD, who suffer from severe dyspnea despite optimal pharmacological and non-pharmacological treatment. Participants will be recruited at CIRO, a center for pulmonary rehabilitation in the Netherlands after they completed a pulmonary rehabilitation program. After providing informed consent, patients will be randomized. Members of the research team who perform measurements will be blinded for treatment allocation.
Patients in the intervention group will receive regular clinical care and morphine SR 10mg, administered twice daily (20mg/24h), which can be increased after one or two weeks to three times per day 10mg (30mg/24h) in non-responders. Patients will be defined as non-responders if the mean dyspnea numeric rating scale (NRS) score was not reduced by 1 point in comparison with baseline. The control group will receive regular clinical care and placebo medication. Patients will receive morphine or placebo for four weeks. In addition, both groups will receive a prescription for a laxative and metoclopramide at the start of the intervention and will be instructed to adjust the dose as needed.
When the intervention period has ended, participants can choose to continue morphine treatment. They will be followed for twelve weeks to assess their healthcare use, use of morphine and number of adverse effects and exacerbations.
Measurements at baseline will include: demographics, medical history, medication, co-morbidities, exercise capacity, respiratory parameters, generic and disease-specific health-related quality of life (HRQoL), severity of dyspnea, sensory and affective dimensions of dyspnea, impact of dyspnea, cognition, level of daytime sleepiness, and functional capacity. A member of the research team will visit patients after 1 and 2 weeks in their home environment to assess adverse effects, compliance, exacerbations, disease-specific HRQoL, mobility, severity of dyspnea, and some respiratory parameters. A member of the research team will call the patient after 2 days and 3 weeks to assess adverse effects, compliance, exacerbations, and severity of dyspnea. After 4 weeks the following measurements will be performed: respiratory parameters, exercise capacity, general and disease-specific HRQoL, sensory and affective dimensions of dyspnea, impact of dyspnea, functional capacity, and adverse effects. Overnight oximetry will be performed in the home environment at baseline and after four weeks. A diary for costs and healthcare use will be filled in during four weeks.
Measurements during the twelve weeks following the intervention include: retrospective cost questionnaire, generic and disease-specific quality of life severity of dyspnea and adverse effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of COPD according to the current Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (GOLD);
- •Optimal pharmacological treatment, including including treatment with a combination of a long-acting muscarinic antagonist and an ultra-long-acting β-agonist;
- •Grade 3 or 4 dyspnea on the mMRC dyspnea scale;
- •Optimal non-pharmacological treatment defined as completed a comprehensive pulmonary rehabilitation program.
排除标准
- •History of substance misuse;
- •Exacerbation of COPD within two weeks of study enrolment;
- •Waiting list for lung transplantation;
- •Pregnant or childbearing potential not using contraception;
- •Renal failure (creatinine clearance <15mL/min);
- •Not being able to read or fill in the questionnaires or diary;
- •Allergy for morphine or its excipients;
- •Concomitant use of irreversible MAO blockers;
- •Use of opioids;
- •History of convulsions;
- •Head injury;
- •Intestinal obstruction;
- •Gastroparesis;
- •Liver disease.
研究组 & 干预措施
control
placebo
干预措施: placebo (Drug)
intervention
sustained release morphine
干预措施: sustained release morphine (Drug)
结局指标
主要结局
Disease-specific health-related quality of life (COPD Assessment Test (CAT))
时间窗: sixteen weeks
Change in disease-specific health-related quality of life in four weeks measured with CAT
Change in partial pressure of CO2 (pCO2)
时间窗: four weeks
Change in pCO2 in four weeks
Change in partial pressure of O2 (pO2)
时间窗: four weeks
Change in pO2 in four weeks
Pulse oximetric saturation (SpO2)
时间窗: four weeks
Change in SpO2 in four weeks
Transcutaneous carbon dioxide (PtcCO2)
时间窗: four weeks
Change in PtcCO2 in four weeks
Oxygen saturation during the night
时间窗: four weeks
Change in oxygen saturation during the night in four weeks using overnight oximetry
Respiratory rate
时间窗: four weeks
Change in respiratory rate in four weeks
次要结局
- Cognition (Montreal Cognitive Assessment, (MoCA)(four weeks)
- distance walked in 6 Minute Walking Test (6-MWT)(four weeks)
- Intake of medication(four weeks)
- Care dependency (Care Dependency Scale (CDS)(four weeks)
- Mobility (Timed 'Up & Go' (TUG) test)(four weeks)
- Sensory and affective dimensions of dyspnea (Multidimensional Dyspnea Profile (MDP)(four weeks)
- Impact of dyspnea (Pulmonary Functional Status and Dyspnea Questionnaire, PFSDQ-M)(four weeks)
- Severity of dyspnea (Numeric Rating Scale (NRS)(sixteen weeks)
- Daytime sleepiness (Epworth Sleep Questionnaire)(four weeks)
- Number of patients with adverse effects(sixteen weeks)
- Number of exacerbations(sixteen weeks)
- Cost of healthcare use in euro's(sixteen weeks)