Double Bedtime Dosing During Immediate-release Morphine Administration to Cancer Patients
Information source: Norwegian University of Science and Technology
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cancer
Intervention: single dose Morphine (Drug); double dose Morphine (Drug); placebo (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Norwegian University of Science and Technology Official(s) and/or principal investigator(s): Paal Klepstad, Md,PhD, Principal Investigator, Affiliation: St.Olavs University Hospital, Norway
Summary
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
Clinical Details
Official title: 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
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double-Blind, Primary Purpose: Treatment
Primary outcome: Primary efficacy variablePatient rating of average pain intensity during night measured on a 11-point nu-meric rate scale
Secondary outcome: Secondary efficacy variablesPain 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 Number of episodes being awake during night Rating of pain intensity measured on a 11-point numeric rate scale when being awake at night Overall rating of side effects (nausea, xerostomia, tiredeness) during night meas-ured on 11-point numeric rate scales Pain preference of treatments: 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 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
Detailed description:
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.
Besides a clinical study it is also relevant to obtain pharmacokinetic observations during
double bedtime and regularly IR morphine dosing. Repeated blood sampling will disturb the
patients during night and hence confound the clinical observations (e. g. sleep quality).
Consequently, the blood samples will not be obtained in the same dosing interval where the
clinical data are obtained.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- 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.
Locations and Contacts
St Olavs University Hospital, TRondheim 7006, Norway
The Norwegian Univeristy of tecknology and science, Trondheim 7006, Norway
Additional Information
Starting date: April 2002
Last updated: April 7, 2015
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