ANZCTR - Registration

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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

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]

NIL

Universal Trial Number (UTN)

Trial acronym

RECOGNISED

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Depression

Delirium

Postoperative Cognitive Dysfunction

Condition category

Condition code

Anaesthesiology

Anaesthetics

Neurological

Dementias

Surgery

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]

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]

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]

Neuropsychological testing at baseline (prior to surgery), Day 7 and 3 months postoperatively.

Primary outcome [2]

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]

Neuropsychological assessment at baseline, day 7 and 3 months.

Secondary outcome [1]

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]

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]

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]

Neuropsychological assessment at 1-3 years postoperatively.

Secondary outcome [3]

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]

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]

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]

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]

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]

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

Sex

Both males and females

Can healthy volunteers participate?

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

5/06/2015

Date of last participant enrolment

Anticipated

5/06/2017

Actual

3/01/2018

Date of last data collection

Anticipated

Actual

2/07/2019

Sample size

Target

145

Accrual to date

Final

145

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

St Vincent's Hospital (Melbourne) Ltd - Fitzroy

Recruitment postcode(s) [1]

3065 - Fitzroy

Funding & Sponsors

Funding source category [1]

Other Collaborative groups

Name [1]

Australian and New Zealand College of Anaesthetists

Address [1]

630 St Kilda Road
Melbourne
3004
VICTORIA

Country [1]

Australia

Primary sponsor type

Hospital

Name

St Vincent's Hospital

Address

PO Box 2900
Fitzroy
VIC 3065

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

St Vincent's Hospital

Ethics committee address [1]

PO Box 2900
Fitzroy
VIC 3065

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

16/10/2014

Approval date [1]

12/12/2014

Ethics approval number [1]

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

A/Prof David Scott

Address

St Vincent's Hospital
PO Box 2900
Fitzroy VIC
3065

Country

Australia

Phone

+61 3 9231 4252

Fax

[email protected]

Contact person for public queries

Name

Erika Fortunato

Address

St Vincent's Hospital
PO Box 2900
Fitzroy VIC
3065

Country

Australia

Phone

+61 3 9231 2072

Fax

[email protected]

Contact person for scientific queries

Name

Lisbeth Evered

Address

St Vincent's Hospital
PO Box 2900
Fitzroy VIC
3065

Country

Australia

Phone

+61 3 9231 2251

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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?

Doc. No.	Type	Email
6321	Study protocol	[email protected]
6322	Statistical analysis plan	[email protected]
6323	Informed consent form	[email protected]
6324	Clinical study report	[email protected]
6325	Ethical approval	[email protected]
6326	Analytic code	[email protected]

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Examining Subjective Psychological Experiences of Postoperative Delirium in Older Cardiac Surgery Patients.	2023	https://dx.doi.org/10.1213/ANE.0000000000006226

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically