Double Bedtime Dosing During Immediate-Release Morphine Administration to Cancer Patients

This study has been completed.
Sponsor:
Information provided by:
Norwegian University of Science and Technology
ClinicalTrials.gov Identifier:
NCT00201539
First received: September 16, 2005
Last updated: August 22, 2008
Last verified: August 2008
  Purpose

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


Condition Intervention Phase
Cancer
Drug: Morphine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double-Blind
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Norwegian University of Science and Technology:

Primary Outcome Measures:
  • Primary efficacy variable
  • Patient rating of average pain intensity during night measured on a 11-point nu-meric rate scale

Secondary Outcome Measures:
  • Secondary efficacy variables
  • 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
  • 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

Estimated Enrollment: 20
Study Start Date: April 2002
Study Completion Date: February 2008
Primary Completion Date: November 2006 (Final data collection date for primary outcome measure)
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00201539

Locations
Norway
St Olavs University Hospital
TRondheim, Norway, 7006
The Norwegian Univeristy of tecknology and science
Trondheim, Norway, 7006
Sponsors and Collaborators
Norwegian University of Science and Technology
Investigators
Principal Investigator: Paal Klepstad, Md,PhD St.Olavs University Hospital, Norway
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00201539     History of Changes
Other Study ID Numbers: OPI 02/001
Study First Received: September 16, 2005
Last Updated: August 22, 2008
Health Authority: Norway: Norwegian Social Science Data Services

Keywords provided by Norwegian University of Science and Technology:
analgesics, opioid/pharmacokinetics
humans
morphine/therapeutic use*
neoplasms
pain/drugtherapy

Additional relevant MeSH terms:
Morphine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014