Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12610000447055
Ethics application status
Approved
Date submitted
27/05/2010
Date registered
2/06/2010
Date last updated
29/11/2019
Date data sharing statement initially provided
29/11/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
The effect of low dose intravenous premedication (co-induction) on cardiac output and induction of anaesthesia
Scientific title
To explore the effect during induction of anaesthesia of low dose intravenous premedication (co-induction) with a variety of drugs, on cardiac output and the dose of propofol required for loss of consciousness, in patients requiring insertion of arterial line for surgery
Secondary ID [1] 1179 0
Nil
Secondary ID [2] 288161 0
There is no secondary ID.
Universal Trial Number (UTN)
Trial acronym
COS Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anaesthetics 252365 0
Cardiac output changes 252366 0
Condition category
Condition code
Anaesthesiology 237430 237430 0 0
Anaesthetics

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Administration of a small dose of midazolam (0.03mg/kg), propofol (0.4mg/kg), fentanyl (1.5mcg/kg) or placebo by intravenous bolus, 3 minutes prior to induction of anaesthesia by propofol, infused at a rate of 3ml/kg/hr until loss of consciousness as confirmed by syringe drop.
Intervention code [1] 236823 0
Treatment: Drugs
Comparator / control treatment
Saline bolus administered intravenously 3 mins prior to induction.
Control group
Placebo

Outcomes
Primary outcome [1] 253432 0
Amount of induction drug required (as determined by time to LOC x infusion rate of 3ml/kg/hr) to loss of consciousness (LOC) as determined by:
1. Syringe drop and
2. Lack of response to command
Timepoint [1] 253432 0
Time to LOC measured from 'propofol on' time and determined by:
1. Syringe drop (primary indicator)
2. Lack of response to command (every 30 sec until lack of response)
Bi-Spectral Index monitor (BIS) 'below 60' time is also noted and amount of propofol till this point calculated as above.
Primary outcome [2] 257444 0
Change in cardiac output after "coinduction" as assessed by Vigileo ('Minimally Invasive, Arterial Pressure Cardiac Output Monitor'. utilising FloTrac sensor attatched to an Arterial Line).
Timepoint [2] 257444 0
Monitored continually from insertion of arterial line until induction/LOC.
Secondary outcome [1] 262581 0
Nil
Timepoint [1] 262581 0
Nil

Eligibility
Key inclusion criteria
Surgery requiring insertion of arterial line,
American Society of Anesthetist (ASA) rating 1,2 or 3
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Contra-indication to propofol.
Requirement for specific co-induction drug, other than study drug.

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)
Identify patients fitting inclusion criteria; consult with rostered anaesthetist re patient/procedure suitability.
Inform patient of study and seek consent. Allocate sequential study number to patient. Administer drug at defined time. Co-induction drug concealed in covered syringe. Drug administered by 'outside' anaesthetist, and not in front of theatre anaesthetist or researcher.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised randomisation sequence.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/11/2009
Actual
24/11/2009
Date of last participant enrolment
Anticipated
29/01/2016
Actual
15/12/2015
Date of last data collection
Anticipated
Actual
29/01/2016
Sample size
Target
80
Accrual to date
Final
50
Recruitment outside Australia
Country [1] 1855 0
New Zealand
State/province [1] 1855 0
Christchurch

Funding & Sponsors
Funding source category [1] 256158 0
Charities/Societies/Foundations
Name [1] 256158 0
Christchurch Anaesthesia Education Trust
Country [1] 256158 0
New Zealand
Primary sponsor type
Charities/Societies/Foundations
Name
Christchurch Anaesthesia Education Trust
Address
c/o Dr R French,
Department of Anaesthesia,
Christchurch Hospital,
Private Bag 4710,
Christchurch 8011,
New Zealand
Country
New Zealand
Secondary sponsor category [1] 251500 0
None
Name [1] 251500 0
Address [1] 251500 0
Country [1] 251500 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258261 0
Upper South A Regional Ethics Committee
Ethics committee address [1] 258261 0
Ministry of Health
PO Box 3877 Christchurch 4011
Ethics committee country [1] 258261 0
New Zealand
Date submitted for ethics approval [1] 258261 0
01/10/2008
Approval date [1] 258261 0
13/11/2008
Ethics approval number [1] 258261 0
URA/08/10/065

Summary
Brief summary
There is good evidence of a true synergy between midazolam and propofol induction and data suggests that pre-dosing with propofol also reduces induction requirements. However, there has been no measure of the actual cardiac output changes in any human studies apart from that of Adachi et al.
We plan to explore the relationship between cardiac output and induction doses of propofol in more detail and, in particular, to explore the effect of co-induction agents on cardiac output and to further evaluate cardiac output changes around induction of anaesthesia.
Trial website
Nil
Trial related presentations / publications
Kennedy RR, McKellow MA Effect-site sevoflurane concentrations at awakening are close to MAC-awake while end-tidal concentrations are lower. Anesthesiology 2017 Boston Oct 2017 http://www.asaabstracts.com/strands/asaabstracts/abstract.htm?year=2017&index=7&absnum=4770

Kennedy RR, McKellow MA, Williman J Comparing end-tidal and calculated effect-site sevoflurane concentrations at awakening from anaesthesia. International Society for Anesthetic Pharmacology Annual Meeting, Boston, October 2017 https://www.isaponline.org/download_file/382/238

Kennedy RR, McKellow MA, Williman J. A comparison of age-adjusted effect-site volatile anesthetic concentrations and an effect-site volatile and opioid interaction model to describe the time of awakening after volatile anesthesia. Anesthesiology 2015 San Diego October 2015
Kennedy RR, McKellow MA, Williman J, French RA. The distribution of effect-site sevoflurane concentrations at wake-up: a comparison of two systems. International Society for Anesthetic Pharmacology Annual Meeting San Diego October 2015

Kennedy RR, McKellow MA, Williman J, French RA. The influence of covariates on effect-site age-adjusted MAC fraction estimated by GE-Navigator at the point of first response after inhalational anesthesia. International Society for Anesthetic Pharmacology Annual Meeting San Diego October 2015
Public notes

Contacts
Principal investigator
Name 29800 0
A/Prof Dr R Ross Kennedy
Address 29800 0
Dept of Anaesthesia
Christchurch Hospital
Private Bag 4710
Christchurch 8011
Country 29800 0
New Zealand
Phone 29800 0
+64 3 3640288
Fax 29800 0
+64 3 3640289
Email 29800 0
[email protected]
Contact person for public queries
Name 13047 0
Assoc Prof Ross Kennedy/Margie McKellow
Address 13047 0
c/o Department of Anaesthesia
Christchurch Hospital
Private Bag 4710
Christchurch 8011
Country 13047 0
New Zealand
Phone 13047 0
+64 3 3640288
Fax 13047 0
+64 3 3640289
Email 13047 0
[email protected]
Contact person for scientific queries
Name 3975 0
Assoc Prof Ross Kennedy
Address 3975 0
c/o Department of Anaesthesia
Christchurch Hospital
Private Bag 4710
Christchurch 8011
Country 3975 0
New Zealand
Phone 3975 0
+64 3 3640288
Fax 3975 0
+64 3 3640289
Email 3975 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


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
No additional documents have been identified.