Double Bedtime Dosing During Immediate-release Morphine Administration to Cancer Patients: A Randomized, Double-blind Cross-over Comparison of a Double Bedtime Dose Ver-sus Two Standard Doses at Bedtime and at Night
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 2
- 主要终点
- Primary efficacy variable
研究概览
简要总结
This is a double -blind randomized crossover study to provide evidence for the expert advice based recommendation of the Expert Working Group of the European Association for Palliative Care (EAPC) that patients during treatment with IR morphine are given a double dose at bed-time that replaces the next 4-hourly dose during night. In addition to the primary, blinded clinical part of the study, an experimental part is also included. This part consists of two open study days were morphine IR is given in the same fashion as the clinical study. The aim is to study whether pharmacokinetic data supports the clinical data.
The use of a double-bedtime IR morphine dose is equal to regularly scheduled IR morphine every 4-hour during night in respect to pain relief during night for patients with pain caused by malignant disease
详细描述
PROTOCOL
Double bedtime dosing during immediate-release morphine administration to cancer patients:
A randomized, double-blind cross-over comparison of a double bedtime dose versus two standard doses at bedtime and at night
Introduction
Oral morphine is recommended by the World Health Organization for pain control in moderate or strong cancer pain 1. At our hospital we use the practice recommended by the Expert Working Group of the European Association for Palliative Care for introduction of strong opioids with titration with immediate-release (IR) morphine dosed every 4 hour until an optimal balance between analgesia and side effects is achieved. After the optimal daily dose is defined slow-release (SR) morphine in the same total daily morphine dose is started 2. One of the features of the EPAC guidelines is that patients during treatment with IR morphine are given a double bed-time that replaces the next 4-hourly dose during night 2. The rationale behind this recommendation is that giving a double dose will prolong duration of morphine analgesia and eliminate the need for awaking the patient during night. However, this recommendation is based on expert opinion and not evidence from clinical studies 2. Todd et al. has recently presented results that challenge this approach from a cross-over study in which the patients received either a double bedtime dose or regular doses every 4-hour 3. This study showed that patients receiving a double bedtime dose reported more pain, more use of rescue medications and reported inferior sleep quality compared to patients receiving regularly scheduled doses. A limitation of this study was that they did not perform the study blinded and thus consequently the results are subject to bias. It is a need for a placebo-controlled study before the evidence carries enough weight to change current recommendations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Double
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
- •Patients with malignant disease
- •Age more than 18 year
- •Regular use of oral morphine or pain that indicates start of opioids for moderate or severe pain according to the WHO guidelines for treatment of cancer pain
- •Exclusion criteria
- •Known morphine intolerance
- •History of drug abuse
- •Decreased gastrointestinal uptake of oral medications
- •Pregnancy or breast-feeding
- •General health condition, psychiatric disease or cognitive function failure giving that the patient is not competent to complete questionnaires.
排除标准
- 未提供
研究组 & 干预措施
double dose once
double dose immediate-release oral morphine at bedtime in cancer patients, placebo after 4 hours
干预措施: double dose Morphine (Drug)
double dose once
double dose immediate-release oral morphine at bedtime in cancer patients, placebo after 4 hours
干预措施: placebo (Drug)
single dose twice
single dose immediate-release oral morphine at bedtime in cancer patients, second single dose after 4 hrs
干预措施: single dose Morphine (Drug)
结局指标
主要结局
Primary efficacy variable
Patient rating of average pain intensity during night measured on a 11-point nu-meric rate scale
次要结局
- Pain rating of "pain now" before scheduled morning dose measured on a 11-point numeric rate scale
- Number of rescue opioid medications during night
- Patient overall rating of sleep quality during night measured on a 11-point nu-meric rate scale
- Rating of pain intensity measured on a 11-point numeric rate scale when being awake at night
- Secondary efficacy variables
- Pharmacodynamic time-course efficacy of opioids measured by pupillometri will be obtained during two 4-hourly dose intervals and one 8-hour dose interval after a double dose administration
- Time-course of serum concentrations of morphine, morphine-6-glucurnide (M6G) and morphine-3-glucuronide (M3G) will be obtained during two 4-hourly dose intervals and one 8-hour dose interval after a double dose administration
- Number of episodes being awake during night
- Overall rating of side effects (nausea, xerostomia, tiredeness) during night meas-ured on 11-point numeric rate scales
- Pain preference of treatments: