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Trial registered on ANZCTR


Registration number
ACTRN12617001341314
Ethics application status
Approved
Date submitted
14/09/2017
Date registered
21/09/2017
Date last updated
27/08/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Tramadol/Paracetamol (Zaldiar) compared with oxycodone and paracetamol for the management of post-operative pain following major surgery in gynaecology oncology patients
Scientific title
Tramadol/Paracetamol (Zaldiar) compared with oxycodone and paracetamol for the management of post-operative pain following major surgery in gynaecology oncology: comparison of post-operative nausea and constipation
Secondary ID [1] 292888 0
Nil known
Universal Trial Number (UTN)
U1111-1202-1630
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post-operative pain 304734 0
Condition category
Condition code
Anaesthesiology 304048 304048 0 0
Pain management
Cancer 304109 304109 0 0
Cervical (cervix)
Cancer 304110 304110 0 0
Ovarian and primary peritoneal
Cancer 304111 304111 0 0
Womb (Uterine or endometrial cancer)
Cancer 304112 304112 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
• Group A (intervention group)
Patients randomised to group A will have the following post-operative oral medication, once they are deemed suitable for discharge oral analgesia by the treating team:
o Tramadol/paracetamol orally 37.5 mg/325 mg, two tablets 4 times per day (to continue for one week on discharge)

Patients will be asked on day 7 post discharge how many tablets they have not used in that period
Intervention code [1] 299125 0
Treatment: Drugs
Comparator / control treatment
• Group B (usual care group)
Patients randomised to group B will have the following post-operative oral medication, once they are deemed suitable for discharge oral analgesia by the treating team:
o Paracetamol orally 500mg, two tablets 4 times per day (to continue for one week on discharge)
o Oxycodone orally 5mg, one - two tablets as needed (maximum 4 times per day) (to continue for one week on discharge)
Control group
Active

Outcomes
Primary outcome [1] 303381 0
• To compare the rates of post-operative nausea in the two groups

As per the validated International Pain Outcomes questionnaire the following is asked on day 7 and 14 post discharge:
Have you had any of the following side effects (nausea, vomiting, drowsiness, constipation) since your discharge from hospital? Please circle "0" if no; if yes, circle the one number that best shows the severity of each (on a scale of 0-10)
Timepoint [1] 303381 0
7 days post discharge (primary endpoint) and 14 days post discharge
Primary outcome [2] 303382 0
• To compare the rates of post-operative constipation in the two groups

As per the validated International Pain Outcomes questionnaire the following is asked on day 7 and 14 post discharge:
Have you had any of the following side effects (nausea, vomiting, drowsiness, constipation) since your discharge from hospital? Please circle "0" if no; if yes, circle the one number that best shows the severity of each (on a scale of 0-10)
Timepoint [2] 303382 0
7 days post discharge (primary endpoint) and 14 days post discharge
Secondary outcome [1] 338777 0
• To record the rate of any adverse event in each group

As per the validated International Pain Outcomes questionnaire the following is asked on day 7 and 14 post discharge:
Have you had any of the following side effects (nausea, vomiting, drowsiness, constipation) since your discharge from hospital? Please circle "0" if no; if yes, circle the one number that best shows the severity of each (on a scale of 0-10). Other adverse events asked about in the questionnaire are

For each option below, please choose the number that best describes how much ("0" being
never and "10" being all of the time), since your discharge from hospital, pain interfered with
or prevented you from

4a doing activities in bed such as turning, sitting up, changing position
4b breathing deeply or coughing
4c sleeping


Pain can affect our mood and emotions.
For each option below, please choose the number that best shows how much, since your
discharge from hospital, pain caused you to feel. ("0" being never and "10" being all of the
time)

5a Anxious
5b Helpless

Need to seek additional pain relief

Paracetamol (all adverse events are uncommon)
Dermatologic: Skin rash
Endocrine & metabolic: Decreased serum bicarbonate, decreased serum calcium, decreased serum sodium, hyperchloremia, hyperuricemia, increased serum glucose
Genitourinary: Nephrotoxicity (with chronic overdose)
Hematologic & oncologic: Anemia, leukopenia, neutropenia, pancytopenia
Hepatic: Increased serum alkaline phosphatase, increased serum bilirubin
Hypersensitivity: Hypersensitivity reaction (rare)
Renal: Hyperammonemia, renal disease (analgesic)

Oxycodone
Central nervous system: Drowsiness (23%), headache, dizziness (9% to 13%)
Dermatologic: Pruritus (6% to 13%)
Gastrointestinal: Nausea (15% to 23%), constipation (adults 23%), vomiting (12% to 21%)
Miscellaneous: Fever (1% to 11%)


Tramadol
Cardiovascular: Flushing (8% to 16%)
Central nervous system: Dizziness (10% to 33%), headache (4% to 32%), drowsiness (7% to 25%), central nervous system stimulation (7% to 14%), insomnia (2% to 11%)
Dermatologic: Pruritus (3% to 12%)
Gastrointestinal: Constipation (9% to 46%), nausea (15% to 40%), vomiting (5% to 17%), xerostomia (3% to 13%), dyspepsia (1% to 13%)
Neuromuscular & skeletal: Weakness (4% to 12%)
Timepoint [1] 338777 0
7 and 14 days post discharge
Secondary outcome [2] 338778 0
• To determine the rate of readmission

Patients are followed up by our unit with a clinical review 2-6 weeks post op, where they will be asked if they have been admitted to any other unit in the post-operative period. Patients however are discharged with our contact details and readmissions come back to our unit and under the care of our team and so we are aware of them when this happens.
Timepoint [2] 338778 0
7 and 28 days post-operatively
Secondary outcome [3] 338779 0
• To determine the rate of perceived inadequate pain relief in each group

As per the validated International Pain Outcomes questionnaire the following is asked on day 7 and 14 post discharge:

Since your discharge, how well controlled do you feel
your pain has been?
Please choose the percentage (0-100%) that best shows
how much relief you have received from all of your
pain treatments.
Timepoint [3] 338779 0
7 and 14 days post discharge
Secondary outcome [4] 338780 0
• To determine the need to additional pain relief in each group

As per the validated International Pain Outcomes questionnaire the following is asked on day 7 and 14 post discharge:

Since discharge, have you sought additional pain relief other than what you were sent home
with from any of the following

8a Emergency department
8b General practitioner
8c Pharmacist
8d Other

9 Would you have liked to be discharged with more pain treatment that you received?
Timepoint [4] 338780 0
7 and 14 days post discharge

Eligibility
Key inclusion criteria
• Patients planned for major surgery for both benign and malignant in the department of gynaecological oncology will be approached for recruitment into the study.
• Aged 18 or over
• English speaking
• Willingness to give written informed consent, and willingness to participate to and comply with the study.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
• Non-English speaking or unable to provide informed consent
• Patients with a documented allergy or contraindication to any of the drugs included in group A or B
• Patients with a history of a psychological illness or condition such as to interfere with the patient's ability to understand the requirements of the study.

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)
Allocation is concealed by central randomisation by the gynaecology patient management system
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will take place via a dedicated module to the gynaecology patient management system in a 1:1 ratio (intervention: control).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Based on an assumed rate of 40% nausea associated with oxycodone and a rate of 20% associated with tramadol, we calculate that a sample size of 79 in each group is needed to detect a 50% reduction in nausea with a power of 80%. Allowing for a 15% attrition rate, we aim to recruit 93 participants in each group.

Analysis
Analysis will be as intention to treat. Data will be summarised using means and standard deviations or medians, interquartile ranges and ranges for continuous data and frequency distributions for categorical data. Univariate comparisons will be made using independent t-tests for continuous outcomes and Chi-square or Fisher exact tests for categorical comparisons. We plan to conduct a multivariable logistic regression analysis for the nominal primary outcomes, adjusting for the variables below. All tests will be two-sided and a p-value <0.05 will be considered statistically significant for the overall analysis.

Variables
The following factors will be adjusted for
- Age (<65 compared with 65 or older)
- Mode of surgery (open or laparoscopic)
- Use of TAP blocks in the peri-operative period
- Use of PCA in the post-operative period
- Amount of opioid use prior to discharge
- Malignant or benign pathology

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/11/2018
Actual
Date of last participant enrolment
Anticipated
31/07/2019
Actual
Date of last data collection
Anticipated
28/08/2019
Actual
Sample size
Target
186
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 9027 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment postcode(s) [1] 17503 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 297515 0
Hospital
Name [1] 297515 0
Chris O'Brien Lifehouse
Country [1] 297515 0
Australia
Primary sponsor type
Hospital
Name
Chris O'Brien Lifehouse
Address
119-143 Missenden Rd, Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 296522 0
None
Name [1] 296522 0
Address [1] 296522 0
Country [1] 296522 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298614 0
Sydney Local Health District Ethics Review Committee
Ethics committee address [1] 298614 0
575 Canterbury Rd, Campsie NSW 2194, Australia
Ethics committee country [1] 298614 0
Australia
Date submitted for ethics approval [1] 298614 0
14/09/2017
Approval date [1] 298614 0
10/04/2018
Ethics approval number [1] 298614 0

Summary
Brief summary
This study aims to investigate the efficacy and safety of tramadol/paracetamol combined dosing compared with paracetamol and oxycodone for pain management following major surgery in gynaecology oncology patients.

Who is it for?
You may be eligible to join this study if you are a female aged 18 years or more who is planned for major surgery for either benign or malignant tumours in gynaecological oncology.

Study details
Participants in this study will be randomly allocated (by chance) to one of two groups. Participants in one group will take oral Tramadol/paracetamol for post-operative pain management in the week following hospital discharge. Participants in the other group will take oral paracetamol and oxycodone in the week following discharge.

All participants will be followed-up for 28 days in order to evaluate post-operative nausea, constipation, adverse events, hospital re-admission rates, and efficacy of pain relief. We hope to determine whether Tramadol / paracetamol is a safe, effective, and well-tolerated option for post-operative pain management.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 77658 0
Prof Sam Saidi
Address 77658 0
Chris O'Brien Lifehouse
119-143 Missenden Rd, Camperdown NSW 2050
Country 77658 0
Australia
Phone 77658 0
+61285140258
Fax 77658 0
Email 77658 0
[email protected]
Contact person for public queries
Name 77659 0
Emma Allanson
Address 77659 0
Chris O'Brien Lifehouse
119-143 Missenden Rd, Camperdown NSW 2050
Country 77659 0
Australia
Phone 77659 0
+61285140730
Fax 77659 0
Email 77659 0
[email protected]
Contact person for scientific queries
Name 77660 0
Emma Allanson
Address 77660 0
Chris O'Brien Lifehouse
119-143 Missenden Rd, Camperdown NSW 2050
Country 77660 0
Australia
Phone 77660 0
+61285140730
Fax 77660 0
Email 77660 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

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.