Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12606000269538
Ethics application status
Approved
Date submitted
20/06/2006
Date registered
29/06/2006
Date last updated
30/09/2009
Type of registration
Prospectively registered

Titles & IDs
Public title
The use of opioids to relieve dysponea in the palliative care setting.
Scientific title
A prospective, dose ranging effectiveness study of sustained-release opioids in the subjective sensation of dyspnoea in opioid naive patients in the palliative care setting.
Secondary ID [1] 272 0
OID06
Universal Trial Number (UTN)
Trial acronym
Opioids in Dyspnoea
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dyspnoea 1246 0
Condition category
Condition code
Respiratory 1330 1330 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Stage one. Open label dose ranging.
Eligible, consenting patients will be commenced on 10mg Sustained Release (SR) morphine (Kapanol) daily.
A diary will be completed twice daily by the participant for 2 days prior to intervention and then for 7 days. On Day 7 the participant will be visited at home and assessed for;
1. Side effects. Little or no side effects will continue the assessment.
2. Benefit. The participant will then be assessed for benefit from the intervention. No benefit will lead to an increased dose of SR morphine by 10mg for a further 7 days.
Participants will continue increasing doses of SR morphine until a dose provides benefit without side effects (to a maximum of 30mg daily). If participants continue to 30mg without side effects, but also without benefit they exit the study at that point and do not continue to stage 2.

Stage two. Long term effectiveness study.
Eligible participants will have reached a SR morphine dose where side effects are absent (or acceptable/minimal) and benefit has been established. Participants will remain on the dose established as part of Stage one.
A diary will be completed at weekly intervals to record ongoing dyspnoea scores, ongoing acceptability, and the emergence of any complications. In addition, participants will be monitored by telephone weekly for 2 months, then monthly until exit from the study.
Stage two will continue until
• Participant withdraws
• The participant is withdrawn, if the AKPS score falls to 30 or below
• Study completion; until participant numbers have been reached,.
• Or until death
Follow-up will include file review for hospitalisation, cessation of opioids, and introduction of other therapies such as oxygen.
Intervention code [1] 1153 0
Treatment: Drugs
Comparator / control treatment
No comparator.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 1817 0
Sensation of dyspnoea as average of morning scores
Timepoint [1] 1817 0
Monthly of previous 3 days.
Primary outcome [2] 1818 0
Sensation of dyspnoea as average of the evening scores
Timepoint [2] 1818 0
Monthly of previous 3 days.
Secondary outcome [1] 3182 0
To document and compare differential side effects and participant burden from varying doses. A safety monitoring telephone call will be made on day 4. On Day 7 the participant will be visited at home and assessed for;
1. Side effects. Unacceptable side effects will end the intervention as the participant experienced side effects from the lowest possible dose. Participation will end. Little or no side effects will continue the assessment.
2. Benefit. The participant will then be assessed for benefit from the intervention.
Timepoint [1] 3182 0
Secondary outcome [2] 3183 0
To document and determine the long term benefit of the dose. A diary will be completed at weekly intervals to record ongoing dyspnoea scores, ongoing acceptability, and the emergence of any complications.
Timepoint [2] 3183 0
In addition, participants will be monitored by telephone weekly for 2 months, then monthly until exit from the study.

Eligibility
Key inclusion criteria
Specialist relevant has assessed participant to have received maximal treatment (including reversing anaemia) • On stable medications for the previous 7 days• Participant has dyspnoea score greater than or equal to 2 on the Modified Medical Research Council dyspnoea scale • In the treating clinician's estimation, the participant has a prognosis of at least one month.• On stable oxygen needs.
Minimum age
18 Years
Maximum age
Not stated
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Pregnancy, any chance of pregnancy, or breastfeeding• On regular opioid medications, including codeine preparations. • Confusion (MMSE<24/30)• AKPS score of <50• Uncontrolled nausea or vomiting.• True adverse reaction(s) or hypersensitivity to previous opioids.• A creatinine clearance of <15ml/min. • Gastrointestinal obstruction.• Concomitant use of Monoamine Oxidase Inhibitor(s) (MAOIs) in the last 2 weeks.• Past history of substance misuse• Unwilling or unable to complete study measures.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Open label
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3 / Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
3/07/2006
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 1457 0
Hospital
Name [1] 1457 0
Repatriation General Hospital
Country [1] 1457 0
Australia
Primary sponsor type
Hospital
Name
Repatriation General Hospital
Address
Country
Australia
Secondary sponsor category [1] 1286 0
None
Name [1] 1286 0
None
Address [1] 1286 0
Country [1] 1286 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 2835 0
Repatriation General Hospital
Ethics committee address [1] 2835 0
Daw Park, SA 5051
Ethics committee country [1] 2835 0
Australia
Date submitted for ethics approval [1] 2835 0
Approval date [1] 2835 0
11/05/2006
Ethics approval number [1] 2835 0
05/06

Summary
Brief summary
Breathlessness is a very distressing and difficult symptom commonly experienced towards the end of life. There are published research findings to show that the use of low dose long acting morphine can help the sensation of breathlessness, without side effects such as drowsiness and respiratory depression. There are now even lower doses of sustained release morphine available than when initial studies were done which may offer similar benefits and potentially fewer side effects. Initial studies in this area were short (one week) and long term benefits and side effects have not been well studied.
This study will try to determine the optimal dose of morphine for breathlessness, which may be lower or higher than those previously reported in the literature, and if there is long term benefit. This will be done through the use of a 2 stage study. In stage 1, consenting participants will start on a small dose of morphine for one week, and then slowly increase the dose if there has been no benefit over a period of up to 3 weeks according to the participant reports of breathlessness and side effects. Participants will be asked to complete a simple twice daily diary throughout stage one, and will be monitored by visits to their home weekly and telephone calls between visits by the study nurse. When participants have been on a dose of morphine for one week which provides relief from breathlessness, without side effects, they will be entered into the second stage of the study.
The second stage will ask participants to continue on the morphine dose determined in stage one long term to determine if that dose continues to provide benefit over a prolonged period. Participants will be monitored via regular telephone calls for the duration of the study or until the participant withdraws. They will also be asked to maintain a simple weekly diary for this time to provide ongoing information about their response to the morphine and any side effects.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 35285 0
Address 35285 0
Country 35285 0
Phone 35285 0
Fax 35285 0
Email 35285 0
Contact person for public queries
Name 10342 0
Belinda Fazekas
Address 10342 0
Southern Adelaide Palliative Services
700 Goodwood Road,
Daw PArk, SA, 5041
Country 10342 0
Australia
Phone 10342 0
08 8275 1057
Fax 10342 0
08 8374 0350
Email 10342 0
[email protected]
Contact person for scientific queries
Name 1270 0
Belinda Fazekas
Address 1270 0
Southern Adelaide Palliative Services
700 Goodwood Road
Daw Park SA 5041
Country 1270 0
Australia
Phone 1270 0
08 8275 1057
Fax 1270 0
08 8374 0350
Email 1270 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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