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

NCT ID: NCT00201539

Last Updated: 2015-04-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-04-30
• Study Completion Date: 2008-02-29

Brief 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

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.

Conditions

Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

double dose once

double dose immediate-release oral morphine at bedtime in cancer patients, placebo after 4 hours

Group Type: ACTIVE_COMPARATOR

double dose Morphine

Intervention Type: DRUG

placebo

Intervention Type: DRUG

purchased from the manufacturer of morphine tablets (Nycomed Pharma, Oslo, Norway)

single dose twice

single dose immediate-release oral morphine at bedtime in cancer patients, second single dose after 4 hrs

Group Type: EXPERIMENTAL

single dose Morphine

Intervention Type: DRUG

Interventions

single dose Morphine

Intervention Type: DRUG

double dose Morphine

Intervention Type: DRUG

placebo

purchased from the manufacturer of morphine tablets (Nycomed Pharma, Oslo, Norway)

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Norwegian University of Science and Technology

OTHER

Sponsor Role: lead

Principal Investigators

Paal Klepstad, Md,PhD

Role: PRINCIPAL_INVESTIGATOR

St.Olavs University Hospital, Norway

Locations

The Norwegian Univeristy of tecknology and science

Trondheim, Trondheim, Norway

St Olavs University Hospital

Trondheim, , Norway

Countries

Norway

References

Dale O, Piribauer M, Kaasa S, Moksnes K, Knobel H, Klepstad P. A double-blind, randomized, crossover comparison between single-dose and double-dose immediate-release oral morphine at bedtime in cancer patients. J Pain Symptom Manage. 2009 Jan;37(1):68-76. doi: 10.1016/j.jpainsymman.2007.12.016. Epub 2008 May 27.

Reference Type: RESULT

PMID: 18504090 (View on PubMed)

Other Identifiers

OPI 02/001

Identifier Type: -

Identifier Source: org_study_id