Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12610000893000
Ethics application status
Not yet submitted
Date submitted
18/10/2010
Date registered
20/10/2010
Date last updated
20/10/2010
Type of registration
Prospectively registered

Titles & IDs
Public title
A Single Patient Multiple Cross-Over Study To Determine The Efficacy Of Paracetamol In Relieving Pain Suffered By Patients With Advanced Cancer Taking Regular Opioids.
Scientific title
A Single Patient Multiple Cross-Over Study To Determine The Efficacy Of Paracetamol In Relieving Pain Suffered By Patients With Advanced Cancer Taking Regular Opioids.
Secondary ID [1] 252901 0
None
Universal Trial Number (UTN)
None
Trial acronym
None
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Stage Cancer Patients 258437 0
Condition category
Condition code
Cancer 258602 258602 0 0
Other cancer types
Anaesthesiology 258620 258620 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The Intervention treatment will be SR paracetamol 665 mg tabs (encapsulated) to be taken orally with water.

The patient will be randomly assigned to one drug. The patient will then be administerd the drug 3 to 4 times daily in a 3 day period. The drug will then be switched. The patient will then be administered the second drug 3 to 4 times daily for a 3 day period. The 6 day period is called a cycle. The cycle will be repeated 3 times.

A washout period will be registered on the first day of each 3 day period. On these day, pain scores will not be included in the final analysis.
Intervention code [1] 257433 0
Treatment: Drugs
Comparator / control treatment
A matching placebo. The Placebo will be taken orally with water.

The patient will be randomly assigned to one drug. The patient will then be administerd the drug 3 to 4 times daily in a 3 day period. The drug will then be switched. The patient will then be administered the second drug 3 to 4 times daily for a 3 day period. The 6 day period is called a cycle. The cycle will be repeated 3 times.

A washout period will be registered on the first day of each 3 day period. On these day, pain scores will not be included in the final analysis.
Control group
Placebo

Outcomes
Primary outcome [1] 259450 0
The primary outcome is an average pain score measured by a Brief Pain Inventory (BPI). This 11-point numerical scale encompasses an assessment of average pain, worst pain, pain right now and pain relief as well as the impact on daily functioning. The BPI has demonstrated reliability and validity across cultures and languages. A clinically significant response is a BPI average score reduction of 2 points from baseline score
Timepoint [1] 259450 0
The BPI will be measured 24 hours preceding the trial. The BPI will also be measured daily. The mean average pain scores of paracetamol cycles will be compared with the mean average pain scores in placebo cycles.
Secondary outcome [1] 266006 0
The number of breakthrough doses in a single day while patient is on trial. A breakthrough dose is defined as an unregular opiod dose required by the patient due to uncontrolled pain while on trial.
Timepoint [1] 266006 0
The breakthrough dose will be recorded by the patient daily in the patient diary. The number of regular opoid doses for the patient will be determined by there physicain before trial conmencement.
Secondary outcome [2] 266007 0
The Patient Global Impression of Changes is a patient rated 7 point scale provides information about the patient perception of their change in pain, specifically their improvement since the commencement of the study. This
will allow the investigators to compare the pain rating using the Numerical Rating Scheme (NRS) with patient perception of improvement. The results of this scale over the study period will assist to determine the clinical significance of any improvement seen.
Timepoint [2] 266007 0
The Patient Global Impression of Change will be measured at the end of each 6 day cycle. Consequently, measurements will be taken on day 6,12 and 18 of the trial.

Eligibility
Key inclusion criteria
a) aged >18 years
b) a clinical diagnosis of chronic cancer-related pain with a Brief Pain Inventory (BPI) average pain score of < 3 over previous 24 hours;
c) taking a regular dose of opioid analgesia (excluding codeine or tramadol) with no change in baseline opioid dose in the 48 hours prior to study
d) no more than three doses of breakthrough opioid/day in the 48 hours prior to trial commencement and no increase in dose of breakthrough during this time
e) a stable dose of other regular pain medications (i.e. coanalgesics) for at least 48 hours prior to trial commencement. Patients already on paracetamol are eligible, but must also stop paracetamol 3 days before the trial;
f) no intervention e.g. radiotherapy, chemotherapy, surgery that might alter pain levels during the 2 weeks prior to the study period or plans to undergo such during the study period;
g) an intact Gastro Intestinal tract (necessary for absorption of extended release preparations), i.e. no bowel obstruction, no colostomy/ileostomy
h) ability to give fully informed written consent and complete all trial requirements including daily pain diaries.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
a) liver function (Aspartate Transaminase (AST), Alanine Transaminase (ALT)) >1.5x upper limit of normal, total bilirubin outside normal range;
b) allergy or sensitivity to paracetamol
c) cognitive impairment that in the clinician’s opinion would preclude fully informed consent or ability to complete study requirements
d) life expectancy less than 6 weeks
e) a poor understanding of written or spoken English that would preclude completion of all trial requirements

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
A suitable candidate for the trial will be detected by physicians or research nurses in the palliative care wards and services in selected Queensland Hospitals. The patient will be given fully informed consent. Once consent is obtained, the patient will be screened to determine if the patient meets the selection/exclusion criteria. If the patient meets the selective criteria, the patient will be given a script to be filled by the hospital pharmacy. The intervention and placebo will be packaged in identical bottles. The bottles will be defined by a set of numbers on the lid and bottle. The pharmacy will have a record of the bottle number and medication in that bottle. The order of intervetion is randomly determined within the pharmacy.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The hospital pharmacy will use a randomly computer generated code to determine the randomisation of the intervention.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
This is a single patient trial. In a Single Patient trial, the patient typically undergoes 3 pairs of treatment periods. As paracetamol has a short half life, the clinical effect is rapidly evident. Therefore, an appropriate duration of each “treatment” period is 3 days (thus each treatment pair is 6 days), making a total of 18 days for patients who complete the full trial. (Patients who fail to complete the full trial will contribute completed cycles to the final analysis). In order to account for medication or placebo “wash out”, no measure of efficacy is taken on the first day of each 3-day period. The order of drugs in each cycle will be determined by random allocation, blinded to both clinician and patient. Patients complete a daily diary recording symptom scores using validated measures for dry mouth and related symptoms, the presence of any side effects, which treatment they prefer, and their estimate of which drug they believe they are taking at the time. At the end of the trial, the order of medications within each of the three cycles is unmasked, and compared with the patient’s observations. Repeated results in the same direction favouring the treatment can be reported in terms of a probability that the result is true. The clinical importance of the result is described by comparing the result to a predetermined clinically important change.
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
1/11/2010
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 3351 0
4101
Recruitment postcode(s) [2] 3352 0
4305
Recruitment postcode(s) [3] 3353 0
4215
Recruitment postcode(s) [4] 3354 0
4029

Funding & Sponsors
Funding source category [1] 257870 0
Government body
Name [1] 257870 0
National Health and Medical Research Council
Country [1] 257870 0
Australia
Primary sponsor type
University
Name
The University of Queensland
Address
The University of Queensland
Building 8
11 Salisbury Road
IPSWICH QLD 4305
Country
Australia
Secondary sponsor category [1] 257071 0
Hospital
Name [1] 257071 0
Mater Hospital
Address [1] 257071 0
Mater Hospital
Raymond Terrace
South Brisbane Qld 4101
Country [1] 257071 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 259899 0
Ethics committee address [1] 259899 0
Ethics committee country [1] 259899 0
Date submitted for ethics approval [1] 259899 0
15/08/2010
Approval date [1] 259899 0
Ethics approval number [1] 259899 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31796 0
Address 31796 0
Country 31796 0
Phone 31796 0
Fax 31796 0
Email 31796 0
Contact person for public queries
Name 15043 0
Professor Geoffrey Mitchell
Address 15043 0
The University of Queensland
Ipswich Campus
Building 12, Level 4, Room 407
11 Salisbury Road
Ipswich, QLD
4305
Country 15043 0
Australia
Phone 15043 0
+61 0412 775 117
Fax 15043 0
Email 15043 0
[email protected]
Contact person for scientific queries
Name 5971 0
Professor Geoffrey Mitchell
Address 5971 0
The University of Queensland
Ipswich Campus
Building 12, Level 4, Room 407
11 Salisbury Road
Ipswich, QLD
4305
Country 5971 0
Australia
Phone 5971 0
+61 0412 775 117
Fax 5971 0
Email 5971 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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