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

April 7, 2015 updated by: Norwegian University of Science and Technology

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Norway
      • TRondheim, Norway, 7006
        • St Olavs University Hospital
      • Trondheim, Norway, 7006
        • The Norwegian Univeristy of tecknology and science

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: double dose once
double dose immediate-release oral morphine at bedtime in cancer patients, placebo after 4 hours
Drug: double dose Morphine
Drug: placebo
purchased from the manufacturer of morphine tablets (Nycomed Pharma, Oslo, Norway)
Experimental: single dose twice
single dose immediate-release oral morphine at bedtime in cancer patients, second single dose after 4 hrs
Drug: single dose Morphine

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Norwegian University of Science and Technology

Investigators

  • Principal Investigator: Paal Klepstad, Md,PhD, St.Olavs University Hospital, Norway

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2002

Primary Completion (Actual)

November 1, 2006

Study Completion (Actual)

February 1, 2008

Study Registration Dates

First Submitted

September 16, 2005

First Submitted That Met QC Criteria

September 16, 2005

First Posted (Estimate)

September 20, 2005

Study Record Updates

Last Update Posted (Estimate)

April 8, 2015

Last Update Submitted That Met QC Criteria

April 7, 2015

Last Verified

April 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OPI 02/001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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