Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12609000968279
Ethics application status
Approved
Date submitted
9/11/2009
Date registered
9/11/2009
Date last updated
9/07/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
A Randomised Controlled Trial Investigating Possible Additive Analgesic
Effects of Paracetamol in Palliative Patients using Low-dose Strong Opioids
Scientific title
A Randomised Controlled Trial Investigating Possible Additive Analgesic
Effects of Paracetamol in Palliative Patients using Low-dose Strong Opioids
Secondary ID [1] 1126 0
NIL
Universal Trial Number (UTN)
Trial acronym
BSPCC_RCT_Paracetamol2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Analgesic benefits of paracetamol for palliative patients using low-dose strong opioids 252101 0
Condition category
Condition code
Public Health 252307 252307 0 0
Health service research

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All patients will receive five days of paracetamol (two 500mg tablets per oral four times a day) and five days of an identical appearing placebo. The primary outcome, pain, will be assessed subjectively by patients completing a daily diary ( of numerical ratings of pain on an 11 point Likert-type scale with values ranging from 0 (none) to 10 (unbearable), for each of the 5 days of both treatments. In addition, the numbers of breakthrough medications used each day will be recorded. Secondary outcomes of subjective ratings of nausea and vomiting, cognitive impairment (drowsiness and unclear thinking), constipation and overall feeling of well-being will also be assessed using 11 point Likert-type scales. A one day washout period dictates that only data from the last four days of each treatment arm will be analysed to exclude the influence of possible carryover effects.
At the completion of the study patients will be asked to rank their global satisfaction with the two treatments. They will be given the option of continuing with paracetamol and asked the reason for their choice.
Intervention code [1] 241494 0
Treatment: Drugs
Comparator / control treatment
Patients will receive 5 days of active treatment (two oral 500mg tablets) followed by 5 days of identical appearing placebo only without the active ingredient or vice versa, thus each patient acts as their own control
Control group
Placebo

Outcomes
Primary outcome [1] 253181 0
Mean difference in pain ratings as rated on an 11 point Likert-type scale over the 2 treatment arms
Timepoint [1] 253181 0
Participants will keep a daily diary for the 10 day trial period. Mean pain ratings over the last 4 days of the two 5 day treatment conditions (active and placebo) will be computed for each participant
Primary outcome [2] 253182 0
Mean difference in number of breakthrough / rescue medications required by each participant over the 2 treatment arms
Timepoint [2] 253182 0
Participants will keep a daily diary for the 10 day trial period and record all breakthrough / rescue medications. The mean number of breakthrough medications will be compared across treatment conditions using a paired t-test.

In addition, differences in rated pain will be further investigated controlling for number of breakthrough medications required. This is to determine whether any differences that may be found in rated pain are maintained when breakthrough medications are held constant and will be analysed in a regression analysis.
Secondary outcome [1] 262106 0
Mean difference in nausea /vomiting ratings as rated on an 11 point Likert-type scale over the 2 treatment arms
Timepoint [1] 262106 0
Participants will keep a daily diary for the 10 day trial period. Mean nausea/vomiting ratings over the last 4 days of the two 5 day treatment conditions (active and placebo) will be computed for each participant
Secondary outcome [2] 262107 0
Mean difference in cognitive impairment ratings as rated on an 11 point Likert-type scale over the 2 treatment arms
Timepoint [2] 262107 0
Participants will keep a daily diary for the 10 day trial period. Mean cognitive impairment over the last 4 days of the two 5 day treatment conditions (active and placebo) will be computed for each participant
Secondary outcome [3] 262108 0
Mean difference in constipation ratings as rated on an 11 point Likert-type scale over the 2 treatment arms
Timepoint [3] 262108 0
Participants will keep a daily diary for the 10 day trial period. Mean constipation over the last 4 days of the two 5 day treatment conditions (active and placebo) will be computed for each participant
Secondary outcome [4] 262109 0
Mean difference in feelings of overall well-being ratings as rated on an 11 point Likert-type scale over the 2 treatment arms
Timepoint [4] 262109 0
Participants will keep a daily diary for the 10 day trial period. Mean feeling of overall well-beingover the last 4 days of the two 5 day treatment conditions (active and placebo) will be computed for each participant

Eligibility
Key inclusion criteria
1.Patients taking the equivalent of 50mg of oral morphine or less in a 24 hour period
2.Patients on stable (+/- 30% of total daily requirement) doses of opioid and non opioid analgesics for at least one week prior to recruitment
3.Baseline pain score greater than or equal to two
4.Prepared to take oral paracetamol (4 gm daily) if not currently prescribed
5.If currently prescribed, prepared to stop their usual dose of paracetamol and use of any breakthrough medications with a paracetamol additive
6.Ability to give informed consent in English
Mini Mental State Examination score of at least 25 out of 30 (to be repeated at 5 day intervals)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1.Palliative patients less than 18 years of age
2.Patients whose pain is considered clinically to be primarily neuropathic
3.Patients who have received treatments in the two weeks before the study that are likely to impact on pain levels (eg radiotherapy) or who receive such therapy during the study period
4.Expected survival less than 2 weeks
5.Patients clinically jaundiced
6.Patients experiencing regular febrile events
7.Any patient who, in the researchers’ opinion, is unable to comply with the protocol

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)
Central randomisation by phone
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation using a randomisation table created by a software system
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/01/2010
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 2175 0
4355
Recruitment postcode(s) [2] 2176 0
4113
Recruitment postcode(s) [3] 2177 0
4350
Recruitment postcode(s) [4] 2178 0
4114
Recruitment postcode(s) [5] 2179 0
4129
Recruitment postcode(s) [6] 2180 0
4131
Recruitment postcode(s) [7] 2181 0
4178
Recruitment postcode(s) [8] 2182 0
4165
Recruitment postcode(s) [9] 2183 0
4064
Recruitment postcode(s) [10] 2184 0
4102
Recruitment postcode(s) [11] 2185 0
4179
Recruitment postcode(s) [12] 2186 0
4108
Recruitment postcode(s) [13] 2187 0
4555
Recruitment postcode(s) [14] 2188 0
4030
Recruitment postcode(s) [15] 2189 0
4169
Recruitment postcode(s) [16] 2190 0
4073
Recruitment postcode(s) [17] 2191 0
4567
Recruitment postcode(s) [18] 2192 0
4551
Recruitment postcode(s) [19] 2193 0
4558
Recruitment postcode(s) [20] 2194 0
4573
Recruitment postcode(s) [21] 2195 0
4110
Recruitment postcode(s) [22] 2196 0
4103
Recruitment postcode(s) [23] 2197 0
4170
Recruitment postcode(s) [24] 2198 0
4171
Recruitment postcode(s) [25] 2199 0
4077
Recruitment postcode(s) [26] 2200 0
4163
Recruitment postcode(s) [27] 2201 0
4121
Recruitment postcode(s) [28] 2202 0
4073
Recruitment postcode(s) [29] 2203 0
4109
Recruitment postcode(s) [30] 2204 0
4119
Recruitment postcode(s) [31] 2205 0
4104
Recruitment postcode(s) [32] 2206 0
4115
Recruitment postcode(s) [33] 2207 0
4075

Funding & Sponsors
Funding source category [1] 243961 0
Other Collaborative groups
Name [1] 243961 0
Brisbane South Palliative Care Collaborative
Country [1] 243961 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Brisbane South Palliative Care Collaborative
Address
PO Box 4069
Eight Mile Plains
Brisbane QLD 4113
Country
Australia
Secondary sponsor category [1] 251315 0
None
Name [1] 251315 0
Address [1] 251315 0
Country [1] 251315 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 244077 0
Princess Alexandra Hospital
Ethics committee address [1] 244077 0
Office of the Human Research Ethics Committee
Ipswich Road
Wooloongabba QLD 4102
Ethics committee country [1] 244077 0
Australia
Date submitted for ethics approval [1] 244077 0
04/08/2009
Approval date [1] 244077 0
29/08/2009
Ethics approval number [1] 244077 0
HREC/09/QPAH/204

Summary
Brief summary
There is little evidence base to direct physicians as to when to use paracetamol for the management of pain in palliative patients who require opioids. In particular, it is not known whether the addition of eight large paracetamol tablets (4gm) to the daily medications of patients, using low-dose strong opioids, improves pain control or merely adds to patients’ tablet burden. This study is a double-blind randomised controlled trial, designed to investigate any analgesic benefits of paracetamol for patients using low-dose strong opioids. It requires patients to take either 4gm of paracetamol or placebo in addition to their usual daily opioids for five days and then to swap to placebo or 4gm of paracetamol for the next five days. Patients are asked to complete a daily diary throughout the ten day study period that records subjective
and objective measures of pain control, aspects of common opioid side effects and quality of life. These records will be quantitatively analysed for statistical significance using paired t-test.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30455 0
Address 30455 0
Country 30455 0
Phone 30455 0
Fax 30455 0
Email 30455 0
Contact person for public queries
Name 13702 0
Fiona Israel
Address 13702 0
17 McKechnie Drive
Eight Mile Plains Qld 4113
Country 13702 0
Australia
Phone 13702 0
+ 61 7 3169 9875
Fax 13702 0
+ 61 7 3169 9885
Email 13702 0
[email protected]
Contact person for scientific queries
Name 4630 0
A/Prof Liz Reymond
Address 4630 0
17 McKechnie Drive
Eight Mile Plains Qld 4113
Country 4630 0
Australia
Phone 4630 0
+ 61 7 3169 9867
Fax 4630 0
+ 61 7 3169 9885
Email 4630 0
[email protected]

No information has been provided regarding IPD availability


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No Supporting Document Provided



Results publications and other study-related documents

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