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Trial registered on ANZCTR


Registration number
ACTRN12615001074583
Ethics application status
Approved
Date submitted
10/04/2015
Date registered
13/10/2015
Date last updated
8/01/2020
Date data sharing statement initially provided
8/01/2020
Date results information initially provided
8/01/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
Perioperative Ketamine to Reduce Postoperative Delirium and Depression - The RECOGNISED Study
Scientific title
Perioperative Ketamine to Reduce Postoperative Delirium and Depression in elderly patients undergoing cardiac and major vascular surgery (The RECOGNISED Study)
Secondary ID [1] 286505 0
NIL
Universal Trial Number (UTN)
Trial acronym
RECOGNISED
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depression
294719 0
Delirium 294720 0
Postoperative Cognitive Dysfunction 294721 0
Condition category
Condition code
Anaesthesiology 295008 295008 0 0
Anaesthetics
Neurological 295009 295009 0 0
Dementias
Surgery 295010 295010 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants involved in study will be randomly assigned to either a ketamine group or a control group before undergoing cardiac or major vascular surgery. Ketamine is proposed as a neuroprotective drug from delirium and depression postoperatively as they are a common in the elderly population undergoing cardiac and major vascular surgery. Ketamine/saline will be administered intravenously as a single dose (0.5mg/kg) fifteen minutes following anaesthetic induction. No further alterations or additions to anaesthetic or surgical technique are required.
Intervention code [1] 291598 0
Prevention
Comparator / control treatment
Patients who are randomised to the control group will be given a saline dose intravenously. Anaesthetic treatment will be at the discression of the treating anaesthetist that is appropriate to the type of surgery.
Control group
Placebo

Outcomes
Primary outcome [1] 294762 0
To measure the incidence of delirium using the 3 minute Diagnostic Confusion Assessment Method (3D-CAM) in the perioperative period after cardiac and major vascular surgery in patients with baseline cognitive impairment receiving ketamine compared to placebo.
Timepoint [1] 294762 0
Neuropsychological testing at baseline (prior to surgery), Day 7 and 3 months postoperatively.
Primary outcome [2] 296304 0
To measure the incidence of depression in patients with baseline cognitive impairment given ketamine compared to placebo, postoperatively and at 3 months following cardiac and major vascular surgery.
Timepoint [2] 296304 0
Neuropsychological assessment at baseline, day 7 and 3 months.
Secondary outcome [1] 314010 0
To measure circulatory mediators of inflammation sequentially in patients given ketamine compared to placebo and identify any associations with delirium, depression and early postoperative cognitive dysfunction. Blood samples will be analysed using an ELISA for a series of interleukins, tumor necrosis factor-a, C-reactive protein and interferon (alpha, beta and gamma). This is a composite outcome.
Timepoint [1] 314010 0
Neuropsychological testing at baseline and day 7 and 3 months postoperatively. Blood samples will be taken prior to induction, at 30 minutes post surgical incision and at 6, 24 and 48 hours post surgery.
Secondary outcome [2] 378562 0
To assess changes in cognitive function after cardiac and major vascular surgery in patients with baseline cognitive impairment receiving ketamine compared to placebo.
Timepoint [2] 378562 0
Neuropsychological assessment at 1-3 years postoperatively.
Secondary outcome [3] 378563 0
To measure circulatory mediators of inflammation sequentially in patients given ketamine compared to placebo and identify any associations with delirium. Analyses will be exploratory, looking for an association between delirium and a range of cytokines as potential biomarkers (e.g. IFN-a, IFN-ß, IL-1a, IL-8).
Timepoint [3] 378563 0
Blood samples will be taken prior to induction, at 30 minutes post surgical incision, and at 6, 24 and 48 hours post surgery.
Secondary outcome [4] 378564 0
To measure circulatory mediators of inflammation sequentially in patients given ketamine compared to placebo and identify any associations with cognitive decline. Analyses will be exploratory, looking for an association between cognitive decline and a range of cytokines as potential biomarkers (e.g. IFN-a, IFN-ß, IL-1a, IL-8).
Timepoint [4] 378564 0
Blood samples will be taken prior to induction, at 30 minutes post surgical incision, and at 6, 24 and 48 hours post surgery.
Secondary outcome [5] 378565 0
To measure circulatory mediators of inflammation sequentially in patients given ketamine compared to placebo and identify any associations with neuronal injury. Analyses will be exploratory, looking for an association between neuronal injury and a range of cytokines as potential biomarkers (e.g. IFN-a, IFN-ß, IL-1a, IL-8). This change was made prior to enrolment commencement.
Timepoint [5] 378565 0
Blood samples will be taken prior to induction, at 30 minutes post surgical incision, and at 6, 24 and 48 hours post surgery.

Eligibility
Key inclusion criteria
1. Patients age 60 years or older, scheduled for cardiac or major vascular surgery (greater than 2 hours).
2. Mini Mental State Examination score between 16 and 25
3. Provide written and informed consent.
4. Reside within reasonable prosimity to St Vincent's Hospital Melbourne for neuropsychological testing
Minimum age
60 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Prior neurological deficit (eg Stroke)
2. Contraindication to neuropsychological testing such as language, visual or hearing impairment
3. Associated medical problems that may lead to significant complications and subsequent loss to follow-up
4. Anticipated ICU stay greater than 24 hours
5. Patients on psychoactive drugs (not antidepressants)
6. Patients unable to consent independently to their surgery on account of cognitive impairment.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients presenting at cardiac or vascular preadmission clinic at St Vincent's Hospital Melbourne and are eligible will be approached for the research. Once consented patients will be randomised by computer generated random-permuted block sequence to receive either intravenous ketamine 0.5mg/kg or intravenous placebo (saline); the anaesthetist will be blinded to the allocation and all other aspects of clinical management of the patient will be the standard of care. All postoperative assessments will be conducted by researchers blinded to treatment allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
An external person to the study will set up the computer generated random-permuted block sequence for randomisation. Half of the patients recruited will recieve ketamine and the other half are to recieve the placebo. Assignment for each patient will be in a sealed envelope and only made known to the treating anaesthetist. Research staff will be blind for the entirety of the process.
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
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis

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)
VIC
Recruitment hospital [1] 3688 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 9512 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 291071 0
Other Collaborative groups
Name [1] 291071 0
Australian and New Zealand College of Anaesthetists
Address [1] 291071 0
630 St Kilda Road
Melbourne
3004
VICTORIA
Country [1] 291071 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's Hospital
Address
PO Box 2900
Fitzroy
VIC 3065
Country
Australia
Secondary sponsor category [1] 289751 0
None
Name [1] 289751 0
Address [1] 289751 0
Country [1] 289751 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292655 0
St Vincent's Hospital
Ethics committee address [1] 292655 0
PO Box 2900
Fitzroy
VIC 3065
Ethics committee country [1] 292655 0
Australia
Date submitted for ethics approval [1] 292655 0
16/10/2014
Approval date [1] 292655 0
12/12/2014
Ethics approval number [1] 292655 0
HREC-D 151/15

Summary
Brief summary
This study aims to invesitgate the neuroprotective effects of ketamine in elderly patients undergoing cardiac and major vascular surgery. Delirium and depression are common effects of cardiac and major vascular surgery. Ketamine is believed to have a protective effect against delirium and depression. Participants will undergo neuropsychological testing prior to surgery and again at day 7 and 3 months postoperatively. Deliriuma and depression will be measured during patient hospital stay. Additionally, inflammatory bloods will be taken to assess the role inflammation plays in the role of postoperative cognitive dysfunction.
Trial website
http://www.cognition.org.au
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 56422 0
A/Prof David Scott
Address 56422 0
St Vincent's Hospital
PO Box 2900
Fitzroy VIC
3065
Country 56422 0
Australia
Phone 56422 0
+61 3 9231 4252
Fax 56422 0
Email 56422 0
David.SCOTT@svha.org.au
Contact person for public queries
Name 56423 0
Ms Erika Fortunato
Address 56423 0
St Vincent's Hospital
PO Box 2900
Fitzroy VIC
3065
Country 56423 0
Australia
Phone 56423 0
+61 3 9231 2072
Fax 56423 0
Email 56423 0
erika.fortunato@svha.org.au
Contact person for scientific queries
Name 56424 0
A/Prof Lisbeth Evered
Address 56424 0
St Vincent's Hospital
PO Box 2900
Fitzroy VIC
3065
Country 56424 0
Australia
Phone 56424 0
+61 3 9231 2251
Fax 56424 0
Email 56424 0
Lis.EVERED@svha.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
It is intended that the IPD will be made available for this trial but specific details have not yet been ascertained.
What supporting documents are/will be available?
Study protocol
Statistical analysis plan
Informed consent form
Clinical study report
Ethical approval
Analytic code
How or where can supporting documents be obtained?
Type [1] 6321 0
Study protocol
Citation [1] 6321 0
Link [1] 6321 0
Email [1] 6321 0
lis.evered@svha.org.au
Other [1] 6321 0
Attachment [1] 6321 0
Type [2] 6322 0
Statistical analysis plan
Citation [2] 6322 0
Link [2] 6322 0
Email [2] 6322 0
lis.evered@svha.org.au
Other [2] 6322 0
Attachment [2] 6322 0
Type [3] 6323 0
Informed consent form
Citation [3] 6323 0
Link [3] 6323 0
Email [3] 6323 0
lis.evered@svha.org.au
Other [3] 6323 0
Attachment [3] 6323 0
Type [4] 6324 0
Clinical study report
Citation [4] 6324 0
Link [4] 6324 0
Email [4] 6324 0
lis.evered@svha.org.au
Other [4] 6324 0
Attachment [4] 6324 0
Type [5] 6325 0
Ethical approval
Citation [5] 6325 0
Link [5] 6325 0
Email [5] 6325 0
lis.evered@svha.org.au
Other [5] 6325 0
Attachment [5] 6325 0
Type [6] 6326 0
Analytic code
Citation [6] 6326 0
Link [6] 6326 0
Email [6] 6326 0
lis.evered@svha.org.au
Other [6] 6326 0
Attachment [6] 6326 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?
Results – basic reporting
Results – plain English summary