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Trial registered on ANZCTR


Registration number
ACTRN12617000787381
Ethics application status
Approved
Date submitted
17/05/2017
Date registered
30/05/2017
Date last updated
22/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of Ketamine in combination with Dexmedetomidine or Fentanyl on measures of cognition, sedation and behaviour in healthy adults
Scientific title
The Effects of Ketamine Infusion in Combination with Dexmedetomidine or Fentanyl on Acute Pain and Cognitive Functioning in healthy adults
Secondary ID [1] 291921 0
Nil
Universal Trial Number (UTN)
U1111-1196-5847
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Drugged Driving 303246 0
Acute care 303247 0
Neurocognition 303248 0
Condition category
Condition code
Injuries and Accidents 302669 302669 0 0
Other injuries and accidents
Anaesthesiology 302670 302670 0 0
Anaesthetics
Mental Health 302671 302671 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will have two distinct treatment arms, where participants will receive either a combination of intravenous ketamine and Fentanyl, or intravenous ketamine and Dexmedetomidine.

In all cases, participants will begin by receiving a bolus dose of 0.3mg/kg intravenous ketamine, to be immediately followed by a ketamine only intravenous infusion of 0.15mg/kg/hr for one hour (total ketamine infusion of three hours for each study arm). After this one-hour ketamine only period, participants will then receive either:
-Receive three 25mcg intravenous injections of Fentanyl at 1.5, 2 and 2.5 hrs after ketamine infusion commencement (if in KET/FENT arm)
OR
-Receive additional 0.7mcg/kg/hr intravenous infusion of Dexmedetomidine commencing one hour post ketamine-only infusion, for a duration of two hours (if in KET/DEX arm).
Intervention code [1] 298041 0
Treatment: Drugs
Comparator / control treatment
We are comparing the sedating, cognitive and behavioural effects of between the two treatments (KET/FENT or KET/DEX)
Control group
Active

Outcomes
Primary outcome [1] 302073 0
Associations between the treatment combinations (Ketamine/Fentanyl or Ketamine/Dexmedetomidine) and neurocognitive ability (CANTAB computerised battery).
Timepoint [1] 302073 0
After administration of treatment combination (Ketamine/Fentanyl or Ketamine/Dexmedetomidine). Specifically, this will occur at baseline, 1 hour post treatment (following cessation of the ketamine and combination treatment), and 1.5 hours post treatment and at 2 hours-post treatment. This will be assessed using the CANTAB cognitive battery; where reaction time, spatial working memory and verbal recognition memory will be assessed.
Primary outcome [2] 302076 0
Associations between the treatment combinations (Ketamine/Fentanyl or Ketamine/Dexmedetomidine) and objective and subjective sedation (Visual Analogue Scale and Algometer).

Objective and subjective sedation will be taken as a composite.
Timepoint [2] 302076 0
After administration of treatment combination (Ketamine/Fentanyl or Ketamine/Dexmedetomidine). Specifically, this will occur at baseline, 1 hour post treatment commencement, 1.5 hours post combination treatment commencement (both for KET/FENT and KET/DEX) and at 2 hours-post treatment cessation. This will be assessed using the Visual Analogue scale of alertness (CANTAB BATTERY) and the Algometer (in conjunction with a visual pain scale); where pain detection and/or pain tolerance threshold will be assessed.
Primary outcome [3] 302077 0
Associations between the treatment combinations (Ketamine/Fentanyl or Ketamine/Dexmedetomidine) and driving performance (highway driving scenario).
Timepoint [3] 302077 0
After administration of treatment combination (Ketamine/Fentanyl or Ketamine/Dexmedetomidine). Specifically, this will occur at baseline, 1 hour post treatment commencement, 1.5 hours post treatment commencement and at 2 hours-post treatment cessation. This will be assessed using the Forum 8 portable driving simulator. Weaving of the car, expressed as standard deviation of the lateral position (SDLP), standard deviation of speed (SDS, km/h) and lapses will be assessed.
Secondary outcome [1] 334978 0
Level of alertness over time as a function of treatment. This will be assessed using subjective alertness questions which comprise part of the CANTAB battery.
Timepoint [1] 334978 0
After administration of treatment (ketamine combined with either Fentanyl or Dexmedetomidine). Specifically, this will occur at baseline, at 1 hour post Ketamine-only treatment, at 1 hour post-commencement of combination treatment and at 2-hours post treatment

Eligibility
Key inclusion criteria
Aged between 21 and 45 years.
Hold a full drivers licence (no ‘P’ plates).
No known allergic reaction to ketamine or other related opioids.
Have no history of past substance abuse or current abuse of illicit drugs.
Have no pre-existing physical or neurological conditions, no previous or current history of severe psychiatric, cardiac, endocrine, gastrointestinal, or bleeding disorders.
Not currently pregnant or lactating
Minimum age
21 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Inability to speak or read English.
Taking any form of medication within 5 days of admission (except for prophylactic antibiotics, contraceptive pill or other routine medications to treat benign conditions, such as antibiotics to treat acne) and agree not to take any medication throughout the study.
Unable to participate in scheduled visit, treatment plan, tests and other trial procedures according to the protocol.
Current participation in any other trials involving investigational or marketed products within 30 days prior to the screening visit.

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)
Randomisation will be achieved via a secure interactive web based system using permuted block minimisation. It will be stratified to males and females to eliminate baseline discrepancies. A total of 20 patients will be randomised to KET/FENT and 20 patients will be randomised KET/DEX.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
This study will employ a between subjects design, and will be open label.
Phase
Phase 1
Type of endpoint/s
Efficacy
Statistical methods / analysis
Demographic data will be presented with summary statistics (number of participants, mean, standard deviation, median and range). The number and percentage of subjects will be presented for categorical variables.
All statistical tests will be performed two tailed at the 5% significance level and performed using IBM SPSS statistical package. Z scores for the distribution will be calculated for each variable and displayed in histogram form. Out of range values will be recoded as missing values.
Demographic data will be presented with summary statistics (number of participants, mean, standard deviation, median and range). Pressure pain algometer analysis will be reported as mean +/- SEM. Neurocognitive, subjective, sedation index scores and neurobehavioural data derived from the CANTAB task, Algometer and the driving task will be analysed using separate Linear Fixed Effects Models. Appropriate covariance structure will be interpreted as to best fit the data. Time will be entered into the model as the repeated measures factor and CANTAB outcome measures, Algometer scores and driving performance scores will be included as the outcome variable. Where a main effect is observed, post-hoc paired t-tests with Bonferroni correction for multiple comparisons will be conducted to contrast each time point to baseline score.
Correlations between CANTAB VAS scores and performance outcomes on CANTAB tasks and the driving simulator across time points as function of treatment will be conducted using Pearson product moment coefficient r.
Linear regression models will be used to assess associations between whole blood concentrations of both ketamine and norketamine and dexmedetomidine or fentanyl (separate for KET/FENT and KET/DEX) and performance on target CANTAB and driving simulator variables.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
18/07/2017
Actual
14/07/2017
Date of last participant enrolment
Anticipated
17/10/2017
Actual
14/02/2018
Date of last data collection
Anticipated
2/03/2018
Actual
2/03/2018
Sample size
Target
41
Accrual to date
Final
41
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 296427 0
Hospital
Name [1] 296427 0
Monash Medical Centre
Country [1] 296427 0
Australia
Primary sponsor type
Hospital
Name
Monash Medical Centre
Address
Monash Medical Centre
246 Clayton Road
Clayton
Victoria 3168
Country
Australia
Secondary sponsor category [1] 295380 0
None
Name [1] 295380 0
Address [1] 295380 0
Country [1] 295380 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297654 0
Monash Health Human Research Ethics Committee
Ethics committee address [1] 297654 0
Monash Medical Centre 246 Clayton Road Clayton Victoria 3168
Ethics committee country [1] 297654 0
Australia
Date submitted for ethics approval [1] 297654 0
17/05/2017
Approval date [1] 297654 0
07/07/2017
Ethics approval number [1] 297654 0
HREC/17/MonH/230

Summary
Brief summary
Both alone and in combination, the effects of Ketamine, Fentanyl and Dexmedetomidine are effective at providing analgesia to patients in the ICU. However, these drug combinations can potentially also have very important consequences for tasks involving complex cognitive and behavioural ability, which includes making important clinical decisions (in a clinical setting both during and post-treatment), and driving a car (post treatment discharge). Currently, it is unclear which clinically indicated drug combination (either KET/DEX or KET/FENT) has more favourable effects on sedation, alertness and cognitive/neurobehavioral outcomes.

We therefore seek to test whether sub-anaesthetic KET/DEX combination will yield in better analgesic and alertness level when compared to KET/FENT, and if there are any differences in cognitive and neurobehavioral abilities between these drug conditions.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 74722 0
Prof Yahya Shehabi
Address 74722 0
Director of Research,
Critical Care and Peri-Operative Medicine
Monash Health
246 Clayton Road
Clayton, Victoria 3168
Country 74722 0
Australia
Phone 74722 0
+61 3 9594 2730
Fax 74722 0
Email 74722 0
[email protected]
Contact person for public queries
Name 74723 0
Amie Hayley
Address 74723 0
Mail H20
Swinburne University of Technology,
Faculty of Health, Arts and Design
School of Health Sciences
Centre for Human Psychopharmacology
PO Box 218 Hawthorn, Victoria, 3122 Australia
Country 74723 0
Australia
Phone 74723 0
+61 3 9214 5585
Fax 74723 0
Email 74723 0
[email protected]
Contact person for scientific queries
Name 74724 0
Amie Hayley
Address 74724 0
Mail H20
Swinburne University of Technology,
Faculty of Health, Arts and Design
School of Health Sciences
Centre for Human Psychopharmacology
PO Box 218 Hawthorn, Victoria, 3122 Australia
Country 74724 0
Australia
Phone 74724 0
+61 3 9214 5585
Fax 74724 0
Email 74724 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
SourceTitleYear of PublicationDOI
EmbaseDriving Simulator Performance after Administration of Analgesic Doses of Ketamine with Dexmedetomidine or Fentanyl.2019https://dx.doi.org/10.1097/JCP.0000000000001101
EmbaseNeurocognitive performance under combined regimens of ketamine-dexmedetomidine and ketamine-fentanyl in healthy adults: A randomised trial.2019https://dx.doi.org/10.1016/j.pnpbp.2019.109647
N.B. These documents automatically identified may not have been verified by the study sponsor.