CancerPhase 3NCT00201539
Double Bedtime Dosing During Immediate-release Morphine Administration to Cancer Patients
A Phase 3 study testing single dose Morphine and double dose Morphine in people with Cancer, run by Norwegian University of Science and Technology at 2 sites in Norway.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- single dose Morphine and double dose Morphine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19 participants
- Where
- 2 sitesNorway
- Study dates
- Apr 2002to Feb 2008
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
Norway2 sites
The Norwegian Univeristy of tecknology and science
Trondheim, Trondheim, 7006
St Olavs University Hospital
Trondheim, 7006
About this study
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
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
Read the 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
- Being tested
- single dose Morphine, double dose Morphine, placebo
- Keywords
- analgesics, opioid/pharmacokinetics, humans, morphine/therapeutic use*, neoplasms, pain/drugtherapy
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
single dose MorphineDrug
double dose MorphineDrug
placeboDrug
purchased from the manufacturer of morphine tablets (Nycomed Pharma, Oslo, Norway)
| Study group | Role | What they receive |
|---|---|---|
| double dose once | Active comparator | double dose immediate-release oral morphine at bedtime in cancer patients, placebo after 4 hours Receives: Drug: double dose Morphine; Drug: placebo |
| single dose twice | Experimental | single dose immediate-release oral morphine at bedtime in cancer patients, second single dose after 4 hrs Receives: Drug: single dose Morphine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary efficacy variable
Patient rating of average pain intensity during night measured on a 11-point nu-meric rate scale
Secondary outcomes (10)
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2005 (estimated)
- Study startApr 2002
- Primary completionNov 2006
- Study completionFeb 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by Norwegian University of Science and TechnologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Norwegian University of Science and Technology
- Sponsor type
- University, hospital or other
- Investigators
- Paal Klepstad, Md,PhD, Principal investigator, St.Olavs University Hospital, Norway
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00201539
- Sponsor's protocol ID
- OPI 02/001
- Status last verified
- Apr 2015
- First submitted
- 16 Sep 2005
- Last updated
- 8 Apr 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 18504090
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00201539
- Acronym / sponsor ID
- OPI 02/001
- Conditions
- Cancer
- Keywords
- analgesics, opioid/pharmacokinetics, humans, morphine/therapeutic use*, neoplasms, pain/drugtherapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Norwegian University of Science and TechnologyUniversity, hospital or other
- Study start
- Apr 2002
- Primary completion
- Nov 2006 (actual)
- Study completion
- Feb 2008 (actual)
- First posted
- 20 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| double dose once | Active comparator | Drug: double dose Morphine, Drug: placebodouble dose immediate-release oral morphine at bedtime in cancer patients, placebo after 4 hours |
| single dose twice | Experimental | Drug: single dose Morphinesingle dose immediate-release oral morphine at bedtime in cancer patients, second single dose after 4 hrs |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| single dose Morphine | Drug | single dose twice |
| double dose Morphine | Drug | double dose once |
| placebopurchased from the manufacturer of morphine tablets (Nycomed Pharma, Oslo, Norway) | Drug | double dose once |
Primary outcome
Primary efficacy variable
Patient rating of average pain intensity during night measured on a 11-point nu-meric rate scale
10 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2015.
- Results publication: PubMed 18504090Dale 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paal Klepstad, Md,PhD principal investigator
St.Olavs University Hospital, Norway
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing single dose Morphine and double dose Morphine in people with Cancer, run by Norwegian University of Science and Technology at 2 sites in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary efficacy variable. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00201539, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2015; AzTrials last refreshed its copy on 3 Nov 2026.