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Trial registered on ANZCTR


Registration number
ACTRN12616000111471
Ethics application status
Approved
Date submitted
19/01/2016
Date registered
2/02/2016
Date last updated
13/12/2018
Date data sharing statement initially provided
13/12/2018
Date results information initially provided
13/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluation of the effect of targeted mild therapeutic hypercapnia during and after cardiopulmonary bypass on cerebral oxygenation and neuropsychological outcomes
Scientific title
A Pilot, Randomised, Unblinded, Feasibility, Safety and Biochemical and Physiological Efficacy Study of Targeted Mild Therapeutic Hypercapnia in Patients Undergoing Cardiopulmonary Bypass
Secondary ID [1] 288369 0
Nil known
Universal Trial Number (UTN)
Trial acronym
The CO2 in CPB Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiac surgery 297363 0
Low cerebral oxygenation 297364 0
Condition category
Condition code
Cardiovascular 297552 297552 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Following blinded allocation, ETCO2 adjustment to target mild hypercapnia (50-55mmHg) will be made using ventilator settings (respiratory rate) throughout the procedure by the treating anaesthetist. ETCO2 levels, as measured using capnography, are similar to arterial levels - while the patient is on bypass, blood gases will be used to measure blood CO2 levels.
Intervention code [1] 293670 0
Treatment: Other
Comparator / control treatment
Following blinded allocation, ETCO2 adjustment to target mild hypercapnia (35-45mmHg) will be made using ventilator settings (respiratory rate) throughout the procedure by the treating anaesthetist.
Control group
Active

Outcomes
Primary outcome [1] 297107 0
Cerebral oxygenation as measured by Near-Infrared Spectroscopy
Timepoint [1] 297107 0
Five-minutely over the course of the surgery, fifteen-minutely over the 12 hours post-operatively, and continuously for a period of five minutes on days 2 and 3 post-operatively
Secondary outcome [1] 320033 0
Hospital mortality, as recorded from scanned hospital medical records
Timepoint [1] 320033 0
Over the entire hospital stay
Secondary outcome [2] 320034 0
Intensive care unit mortality, as recorded from scanned hospital medical records
Timepoint [2] 320034 0
Over the entire intensive care unit stay
Secondary outcome [3] 320035 0
Hospital length of stay, as recorded from scanned hospital medical records
Timepoint [3] 320035 0
From hospital admission to discharge
Secondary outcome [4] 320036 0
Intensive care unit length of stay, as recorded from scanned hospital medical records
Timepoint [4] 320036 0
From intensive care unit admission to discharge
Secondary outcome [5] 320037 0
Discharge destination, as recorded from scanned hospital medical records
Timepoint [5] 320037 0
At time of discharge from hospital
Secondary outcome [6] 320038 0
Rey Auditory Verbal Learning test score - this test measures short-term auditory-verbal memory and learning
Timepoint [6] 320038 0
Baseline measurement once pre-operatively and assessed again on day five post-operatively
Secondary outcome [7] 320039 0
Trail-Making A & B Tests - this test measures visual attention and task switching
Timepoint [7] 320039 0
Baseline measurement once pre-operatively and assessed again on day five post-operatively
Secondary outcome [8] 320040 0
Grooved Pegboard Test - this test measures manual dexterity
Timepoint [8] 320040 0
Baseline measurement once pre-operatively and assessed again on day five post-operatively
Secondary outcome [9] 320041 0
Mini-Mental State Examination - this test generally measures cognitive impairment
Timepoint [9] 320041 0
Baseline measurement once pre-operatively and assessed again on day five post-operatively

Eligibility
Key inclusion criteria
1. Admitted to the Austin Hospital for elective cardiac surgery
2. Aged 18 years or older
3. Able to speak and read English
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Pre-operative Mini-Mental State Examination score < 24
2. Emergency cases
3. History of neuropsychiatric disorders
4. Contraindications to increased CO2 levels, such as right-sided heart failure, pulmonary hypertension, metabolic acidosis
5. Aortic arch surgery

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)
1. Each envelope will contain a study arm allocation as well as a copy of a simplified version of the study protocol and a Patient Information and Consent Form.
2. Every patient who participates in any study-related procedure will be assigned a unique patient number.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
1. Computer generated sets of random allocations will be produced by the Research Co-ordinator in advance of the study.
2. Randomisation will be by means of sealed envelopes with permuted blocks of variable size.
3. Randomisation will be stratified by type of surgery.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/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] 5115 0
Austin Health - Austin Hospital - Heidelberg

Funding & Sponsors
Funding source category [1] 292719 0
Hospital
Name [1] 292719 0
Austin Hospital
Address [1] 292719 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country [1] 292719 0
Australia
Primary sponsor type
Hospital
Name
Austin Health
Address
Austin Health
145 Studley Road
Heidelberg VIC 3084
Country
Australia
Secondary sponsor category [1] 291450 0
Individual
Name [1] 291450 0
Professor Rinaldo Bellomo
Address [1] 291450 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country [1] 291450 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294208 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 294208 0
Austin Health
145 Studley Road
Heidelberg VIC 3084
Ethics committee country [1] 294208 0
Australia
Date submitted for ethics approval [1] 294208 0
25/11/2015
Approval date [1] 294208 0
06/01/2016
Ethics approval number [1] 294208 0
HREC/15/Austin/504

Summary
Brief summary
Cardiopulmonary bypass (CPB) is commonly used in cardiac surgery to maintain blood flow to the brain. However, loss of pulse pressure during CPB means that brain blood flow may be low and brain oxygen levels may fall. This may be bad and affect brain performance after surgery. Oxygen levels in the brain can be monitored with Near Infrared Spectroscopy (NIRS) and brain performance can be assessed with psychological tests. One way to improve brain blood flow and oxygen levels may be to target a slightly higher carbon dioxide (CO2) concentration in the blood during and after CPB. This is because even a slight increase in CO2 can open up the blood vessels to the brain, increase blood flow to it and increase oxygen levels for brain cells. However, targeting such slightly higher CO2 levels in this setting has not been formally studied.

The aim of this study is to compare the changes in cerebral oxygen levels (SctO2) and psychological test-assessed brain performance when a mildly increased CO2 level is targeted compared with a normal CO2 level during and after CPB. We plan to study forty adult patients having CPB (twenty targeting normal CO2 levels and twenty targeting mildly increased CO2 levels), and to measure their SctO2 and psychological test performance prior to surgery and before hospital discharge.

The information derived from our investigation will be used by doctors to improve oxygen levels in the brain of patients during and after CPB in the future.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 62898 0
Prof Rinaldo Bellomo
Address 62898 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country 62898 0
Australia
Phone 62898 0
+61 3 9496 5992
Fax 62898 0
+61 3 9496 3932
Email 62898 0
rinaldo.bellomo@austin.org.au
Contact person for public queries
Name 62899 0
A/Prof Glenn Eastwood
Address 62899 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country 62899 0
Australia
Phone 62899 0
+61 3 9496 4835
Fax 62899 0
+61 3 9496 3932
Email 62899 0
glenn.eastwood@austin.org.au
Contact person for scientific queries
Name 62900 0
Prof Rinaldo Bellomo
Address 62900 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country 62900 0
Australia
Phone 62900 0
+61 3 9496 5992
Fax 62900 0
+61 3 9496 3932
Email 62900 0
rinaldo.bellomo@austin.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
Pilot feasibility study conducted at one centre.
What supporting documents are/will be available?
No other documents available
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?
No
Results – basic reporting
Results – plain English summary
Trend towards benefit of targeted mild therapeutic hypercapnia (slightly higher than normal targeting of blood carbon dioxide level) on cerebral oxygenation during cardiopulmonary bypass; non-inferior safety outcomes of intervention; finding of ongoing cerebral oxygen desaturation post-operatively across both intervention & control groups.