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Trial registered on ANZCTR


Registration number
ACTRN12609000870257
Ethics application status
Approved
Date submitted
18/06/2009
Date registered
7/10/2009
Date last updated
11/10/2010
Type of registration
Prospectively registered

Titles & IDs
Public title
Using n-of-1 trials to determine the effectiveness of paracetamol in advanced
cancer patients on opioids
Scientific title
advanced cancer patients on opioids using n-of-1 trials to determine the effectiveness of paracetamol compared to placebo
outcome: Difference in mean visual analog scale (VAS) for average pain over the last 24 hours on days 2 and 3 of each cycle pair.
Secondary ID [1] 252849 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
advanced cancer 237064 0
Condition category
Condition code
Cancer 237383 237383 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The patient will undergo 3 pairs of 3 day treatments (cycles), making a total of 18 days. 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 pain scores, side effects, which treatment they prefer, and their estimate of which drug they are taking at the time. Data from days 2 and 3 will be used for analysis of that cycle to allow for washout (so day 1 is use das a washout). The drugs being used are long-acting paracetamol 665 mg, and placebo, orally, two capsules three times daily.

At the end of the trial, the order of medications 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 it to a predetermined clinically important change.
Intervention code [1] 236781 0
Treatment: Drugs
Comparator / control treatment
The comparator is identical placebo 665 mg, orally, two capsules three times daily. At this stage we are working out what the placebo will be made of (an inert filler). The patient will undergo 3 pairs of 3 day treatments (cycles), making a total of 18 days. So 9 days will be on active para- cetamol and 9 days will be on comparator.
Control group
Placebo

Outcomes
Primary outcome [1] 238185 0
Difference in mean VAS for average pain over the last 24 hours on days 2 and 3 of each cycle pair.
Timepoint [1] 238185 0
At the end of each pair of treatment periods
Secondary outcome [1] 242492 0
As for the primary endpoint, but using subscales of the Brief Pain Inventory (BPI) (worst pain, pain over last 24 hours, pain right now); Patient's Global Impression of Change (PGIC), changes in physical performance on the AKPS (Australian Karnofsky Performance Scale); changes in use of breakthrough pain relief; and frequency and type of paracetamol side effects.
Timepoint [1] 242492 0
a) Baseline: Age, sex, cancer diagnosis, duration and site of chronic pain, pre-trial analgesia (dose and frequency) and concomitant medications will be collected.
b) Daily self-recording of VAS, BPI, PGIC, any side effects, number of breakthrough medication doses, and any changes in baseline analgesia or concomitant analgesia. The staff will record AKPS at the end of each three day pair.
c) Patient guess of which drug they are taking after each 3 days, and their preferred medicine at the end of each cycle.
d) Compliance check: medication compliance and extent of diary completion at 18 days.

Eligibility
Key inclusion criteria
Patients aged >18 years, with: 1) a clinical diagnosis of chronic cancer-related pain (predominantly nocioceptive rather than neuropathic in origin, Leeds Assessment of Neuropathic Symptoms and Signs (LANNS) score (27) <12), with a Brief Pain Inventory (BPI) (28) average pain score of = 3; 2) a stable baseline dose of opioid (excluding codeine or tramadol) with no more than 2 breakthrough doses of opioid per day. The opioid dose will have been stable for at least 5 days prior to commencing the trial; 3) a stable dose of other regular medications for at least five days before the trial commences. Patients already on paracetamol are eligible, but must stop paracetamol 3 days before the trial; 4) no intervention eg 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. 5) an intact small bowel (necessary for absorption of extended release preparations), no bowel obstruction 6) satisfactory liver function (Aspartate transaminase (AST), Alanine aminotransferase (ALT) = 1.5x upper limit of normal, total bilirubin within
normal range); 7) no known allergy or sensitivity to paracetamol; 8) ability to give fully informed written consent and complete daily pain diaries.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients with: 1) an alcohol intake of >3 units/day; 2) cognitive impairment that in the clinician’s opinion would preclude fully informed consent or ability to complete study requirements; 3) a poor understanding of written English; 4) life expectancy less than 6 weeks.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 237180 0
Government body
Name [1] 237180 0
National Health and Medical Research Council (NHMRC)
Address [1] 237180 0
National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601
Country [1] 237180 0
Australia
Primary sponsor type
University
Name
The University of Queensland
Address
St Lucia Brisbane Queensland 4072
Country
Australia
Secondary sponsor category [1] 4673 0
None
Name [1] 4673 0
Address [1] 4673 0
Country [1] 4673 0
Other collaborator category [1] 711 0
Hospital
Name [1] 711 0
Gold Coast Hospital
Address [1] 711 0
Gold Coast Health Service District
108 Nerang St
Southport Queensland Brisbane 4215
Country [1] 711 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 239273 0
The University of Queensland
Ethics committee address [1] 239273 0
St Lucia Brisbane Queensland 4072
Ethics committee country [1] 239273 0
Australia
Date submitted for ethics approval [1] 239273 0
Approval date [1] 239273 0
Ethics approval number [1] 239273 0

Summary
Brief summary
This study aims to determine the effectiveness of paracetamol for treating pain relief in people with advanced cancer who are currently taking opioids.


Who is it for?
You can join this study if you have advanced cancer with chronic cancer-related pain and you are currently taking opioids to control the pain.

Trial details
Participants will either start treatment with paracetamol in addition to regular opioids or they will start treatment with a non-active compound (*placebo) plus regular opioids. Participants will then cross-over to receive either placebo (if they started by tak! ing paracetamol) or to receive paracetamol (if they started by taking a placebo).

Participants will undergo 3 pairs of 3 day treatments (cycles), making a total of 18 days. The drugs being used are paracetamol 500 mg, and placebo, orally, two capsules three times daily. Participants complete a daily diary recording pain scores, side effects, which treatment they prefer, and their estimate of which drug they are taking at the time.

The study aims to determine the efficacy of paracetamol in alleviating pain in patients with advanced cancer who are taking routine opioids. It will also allow an evaluation of the study techniques (n-of-1 trial design which is when one patient is randomised from one treatment and then to another to allow comparison) and development of appropriate statistical techniques for the analysis of trial data, and where appropriate, provide a means of adjusting for illness progression.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29772 0
Address 29772 0
Country 29772 0
Phone 29772 0
Fax 29772 0
Email 29772 0
Contact person for public queries
Name 13019 0
Jane Nikles
Address 13019 0
School of Medicine
The University of Queensland
Herston Rd
Herston 4006
Country 13019 0
Australia
Phone 13019 0
61 7 3374 3898
Fax 13019 0
Email 13019 0
uqjnikle@uq.edu.au
Contact person for scientific queries
Name 3947 0
Jane Nikles
Address 3947 0
School of Medicine
The University of Queensland
Herston Rd
Herston 4006
Country 3947 0
Australia
Phone 3947 0
61 7 3374 3898
Fax 3947 0
Email 3947 0
uqjnikle@uq.edu.au

No information has been provided regarding IPD availability
Summary results
No Results