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Trial registered on ANZCTR


Registration number
ACTRN12621000240842
Ethics application status
Approved
Date submitted
3/12/2020
Date registered
8/03/2021
Date last updated
8/03/2021
Date data sharing statement initially provided
8/03/2021
Date results information initially provided
8/03/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
Comparing Oral and Sublingual Ketamine Lozenges as Rescue Analgesics in Adults with Acute Pain
Scientific title
Comparing Oral and Sublingual Ketamine Lozenges as Rescue Analgesics in Adults with Acute pain
Secondary ID [1] 303213 0
nil known
Universal Trial Number (UTN)
Trial acronym
OSKet
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Pain 319195 0
Condition category
Condition code
Anaesthesiology 317160 317160 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Inpatients with acute pain rated as 5 or more on numerical rating scales (NRS) started on ketamine lozenges were recruited after informed consent. The primary aim is to compare clinical efficacy of oral and sublingual ketamine lozenges.

Patients were randomised to receive ketamine 50mg lozenge sublingually with placebo lozenge orally or ketamine 50mg lozenge orally with placebo lozenge sublingually on each treatment day. A pharmacist did the randomisation, enabling researchers administering the treatment over two days to remain blinded. Participants were asked to swallow first lozenge and then suck on second lozenge until it has dissolved completely on both days. Participants were asked the question if the lozenge has dissolved completely on each treatment day. Time to first effect and meaningful effects were documented by research staff. Participants were then given a timer and data collection sheet. Participants were advised on how to score their pain at rest and at set intervals during the trial. Pain scores were self recorded half hourly for first two hours, then hourly for next two hours.


Side effects were recorded for each treatment period.

Patients satisfaction and global impression of change were recorded at the end of each treatment periods by research staff.
Intervention code [1] 318688 0
Treatment: Drugs
Comparator / control treatment
Randomised, double-blind cross-over study design. Patients were randomised to either 50mg sublingual ketamine lozenge and oral placebo lozenge or 50mg oral ketamine lozenge and sublingual placebo lozenge over two treatment days. Placebo treatment used is also a lozenge made of glucose. Participants were asked to either swallow (Oral route) or suck on the placebo lozenge (sublingual route) depending on the treatment days. Placebo lozenges were made to look similar to ketamine lozenges in colour, size and shape. Placebo lozenges were also flavoured to mimic taste of active ketamine lozenges. Patients acted as their own controls. There is a minimum washout of 24 hours between treatment days.
Control group
Placebo

Outcomes
Primary outcome [1] 325243 0
Participants self-reported pain scores using Numeric Pain Rating Scale at rest at set interval.
Timepoint [1] 325243 0
Pain scores prior to treatment as t=0
Pain scores self-recorded at half hourly interval for first two hours, then hourly for next two hours.

Primary outcome [2] 325244 0
Time to first effect
Timepoint [2] 325244 0
Research staff records time to first effect using timer.
Primary outcome [3] 326255 0
Time to meaningful pain relief
Timepoint [3] 326255 0
Research staff records time to meaningful pain relief.
Secondary outcome [1] 387322 0
Global impression of change as per IMPACT statement questioned at end of each treatment day. Participants were asked if they were " better", "unchanged", or "worse" after each treatment day.
Timepoint [1] 387322 0
Research staff conducted study-specific questionnaires at end of each treatment day.
Secondary outcome [2] 390758 0
Side effects were documeneted by research staff at end of treatment period. A list of known side effects to ketamine such as nausea, vomiting, hallucinations, sedations, lightheadedness were asked. Sedation as rated using sedation scale 0-4
Timepoint [2] 390758 0
Assessed at end of treatment period by reseach staff in semi-structured interview.
Secondary outcome [3] 390759 0
Patient satisfaction questionaires using categories: satisfied, unsatisfied used.
Timepoint [3] 390759 0
Research staff assessed participants' satisfaction with treatment day at end of period for both days.

Eligibility
Key inclusion criteria
1) 18years old or above
2) Inpatients with acute breakthrough pain of 5 or more on numerical rating scale who required additional medication and previously responded to sublingual ketamine.
3) able to self-assess pain scores on NRS
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients with known contraindications to ketamine such as: allergy to ketamine; severe cardiovascular disease; history of stroke or cerebral trauma; significant liver disease.

Pregnant women or breastfeeding mothers.

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 by trial pharmacist who prepared the medications to be administered for each treatment period.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Crossover
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Friedman repeated measures ANOVA on ranks test for comparing pain scores at each time points to baseline pain scores for each treatment day.
Random effects regression model was applied to mean pain scores at each time points when comparing differences in the two treatment days.
Random effects regression model also used for comparing global impression of change; patient satisfaction; time to first effect and time to meaningful effects.
Adverse effects were analysed using repeated measures of logistic model

Recruitment
Recruitment status
Completed
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)
WA

Funding & Sponsors
Funding source category [1] 306827 0
University
Name [1] 306827 0
Univertisy of Western Australia
Address [1] 306827 0
UWA Discipline of Anaesthesiology and Pain Medicine
Level 4 MRF Building, Royal Perth hospital
GPO BOX X2213 Perth WA 6847 Australia
Country [1] 306827 0
Australia
Primary sponsor type
University
Name
University of Western Australia
Address
UWA Discipline of Anaesthesiology and Pain Medicine
Level 4 MRF Building, Royal Perth hospital
GPO BOX X2213 Perth WA 6847 Australia
Country
Australia
Secondary sponsor category [1] 307386 0
Hospital
Name [1] 307386 0
Royal Perth Hospital
Address [1] 307386 0
Victoria Square Perth
WA 6000
Country [1] 307386 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306987 0
Royal Perth Hospital Ethics Committee
Ethics committee address [1] 306987 0
Victoria Square, Perth WA 6000
Ethics committee country [1] 306987 0
Australia
Date submitted for ethics approval [1] 306987 0
06/08/2007
Approval date [1] 306987 0
18/01/2008
Ethics approval number [1] 306987 0
EC2007/122

Summary
Brief summary
Case reports and case series have documented efficacy of either sublingual or oral ketamine. They have not been compared with each other in past. The study aims to compare the efficacy between the two routes and their side effects profile in hope of guiding future practice.
Trial website
Trial related presentations / publications

Public notes

Contacts
Principal investigator
Name 105662 0
Dr Chui Chin Chong
Address 105662 0
Royal Perth Hospital
Victoria Square
Perth
WA
6000
Country 105662 0
Australia
Phone 105662 0
+61 892242244
Fax 105662 0
Email 105662 0
chui.chong@health.wa.gov.au
Contact person for public queries
Name 105663 0
Prof Stephan Schug
Address 105663 0
Royal Perth Hospital
MRF building
Perth WA
6000
Country 105663 0
Australia
Phone 105663 0
+61 8 64880000
Fax 105663 0
Email 105663 0
stephan.schug@uwa.edu.au
Contact person for scientific queries
Name 105664 0
Dr Chui Chin Chong
Address 105664 0
Royal Perth Hospital
Victoria Square
Perth
WA
6000
Country 105664 0
Australia
Phone 105664 0
+61 892242244
Fax 105664 0
Email 105664 0
chui.chong@health.wa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All data collected can be shared upon request at authors' discretion.
When will data be available (start and end dates)?
Trial has finished and can be made available upon request to author to Chui.chong@heatlh.wa.gov.au within 5 years after publication at discretion of authors.
Available to whom?
Data can be available to researchers affiliated with universities or hospitals who requests subject to investigators' discretions.
Available for what types of analyses?
Raw data may be used/included in reviews or meta-analysis.
How or where can data be obtained?
Data can be obtained via email request to trial investigators subject to their discretions. Please email chui.chong@health.wa.gov.au. Results are being prepared for publication.
What supporting documents are/will be available?
Informed consent form
Ethical approval
How or where can supporting documents be obtained?
Type [1] 9291 0
Informed consent form
Citation [1] 9291 0
Link [1] 9291 0
Email [1] 9291 0
Other [1] 9291 0
Type [2] 9293 0
Ethical approval
Citation [2] 9293 0
Please see attached ethical approval report from RPH Ethics Committee.
Link [2] 9293 0
Email [2] 9293 0
Other [2] 9293 0
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Yes
Other publication details
Citation type [1] 9722 0
Presentation
Citation/DOI/link/details [1] 9722 0
Presented at ANZCA ASM Melbourne 2013 in the FPM Dean's Prize session.
Attachments [1] 9722 0
Results – basic reporting
Results – plain English summary
Ketamine given sublingually and orally produced similar analgesic effects. Sublingual ketamine has faster onset of action and possibly higher rate of adverse effects.