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Trial registered on ANZCTR


Registration number
ACTRN12611000343909
Ethics application status
Approved
Date submitted
25/03/2011
Date registered
1/04/2011
Date last updated
14/05/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
Trial of a new water soluble intravenous anaesthetic
Scientific title
Induction of anaesthesia with an intravenous injection of PHAX001, a new water soluble anaesthetic compared with propofol for speed of onset and recovery from anaesthesia.
Secondary ID [1] 259860 0
Nil
Universal Trial Number (UTN)
U1111-1120-2898
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dose effect for induction of anaesthesia 265443 0
Condition category
Condition code
Anaesthesiology 265600 265600 0 0
Anaesthetics

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Volunteer subjects will be given an intravenous injection of the test anaesthetic, PHAX001 or propofol in a subject and observer blinded randomised manner. Each subject will receive only one dose of one of the anaesthetic drugs. Doses will be increased or decreased from one subject to the next according to response. Twenty four subjects will be allocated randomly to receive either propofol or PHAX001; n = 12 per group. Two anaesthetists will be involved, one to care for the patient and the other, the drug administering anaesthetist. The drug administering anaesthetist will break the code for each subject in turn from a computer program after all preparations are made for drug injection i.e., after an individual subject and the caring anaesthetist have been screened by a curtain between them and the drug administering anaesthetist; the code will allocate the drug treatment randomly to that subject - propofol or PHAX001. For the first subject randomised to receive the drug they will be given propofol 2 mg/kg or PHAX001 0.55 mg/kg. The observations and measurements listed below will be made. That subject will not receive any more propofol or PHAX001. The dosing for the next subject to receive a particular drug will be determined by the response of the first subject given that drug. If the first subject did not achieve a bispectral index reading on the EEG monitor (BIS) of 50 or less, then for propofol the dose would be 3 mg/kg in the second subject randomised to receive propofol or PHAX001 0.75 mg/kg in the case of the second subject randomised to receive PHAX001. If the first subject did achieve a BIS of 50 or less, then for propofol the dose would be 1 mg/kg and for PHAX001 0.25 mg/kg. Thereafter the dosing will be: 1) a decrease of dose of 25% if all subjects so far treated with that drug achieved a BIS below 49 or, 2) an increase of dose of 25% if none of the subjects so far treated with that drug had achieved a BIS of 50 or less, or, 3) in the case that there have been some subjects treated with this drug that have achieved BIS values of 50 or less than 50 and others with BIS values of greater than 50 then either: a) if the last subject's response was a BIS of 50 or less, then the dose of drug for the next subject to receive this drug will be mid way between that subject's dose and the dose given to the most recent previous subject given that drug and who achieved a BIS of 50 or above. b) In the case of the last response being a BIS of 50 or greater, then the dose of drug for the next subject to receive this drug will be mid way between the dose for that subject and the dose given to the most recent previous subject given that drug who achieved a BIS of 49 or below. 4) The latter will be repeated for each drug series until the dose range variations have become small and five or six subjects have achieved a BIS value of 50 or less having received the same dose +/- 10% of drug. These 6 doses achieving anaesthetic levels of BIS (50 or less) will be combined to calculate the mean +/- sem induction dose. Time for induction of anaesthesia and recovery will be measured using clinical observations and BIS monitoring. Effects on blood pressure, heart rate and respiration will also be measured.
Intervention code [1] 264282 0
Treatment: Drugs
Comparator / control treatment
The commonly used anaesthetic propofol will be used as comparator. Each subject randomised to be treated with propofol will receive one intravenous injection administered in 15 seconds. The initial dose of propofol to be given to the first subject randomised to receive propofol will be 2mg/kg. The dosing for the next subject randomised to receive propofol will be determined by the response of the first subject given that drug. If the first subject did not achieve a bispectral index reading on the EEG monitor (BIS) of 50 or less, then the next subject randomised to receive propofol will receive 3 mg/kg. If the first subject did achieve a BIS of 50 or less, then for the second subject randomised to receive propofol will be given a dose of 1 mg/kg. Thereafter the dosing will be: 1) decrease of dose of 25% if all subjects so far treated with propofol achieved a BIS of 50 or less or, 2) an increase of dose of 25% if all subjects so far treated with propofol had not achieved a BIS of 50 or less or, 3) in the case that there have been some subjects treated with this drug that have achieved BIS values of 49 or less and others with BIS values that have not fallen below 50 then either: a) if the last subject's response was a BIS of 50 or less, then the dose of propofol for the next subject to receive this drug will be an average of that subject's dose and the dose given to the most recent previous subject given propofol who maintained a BIS value of 50 or above. b) In the case of the last response to propofol being a BIS of 50 or greater, then the dose of drug for the next subject to receive propofol will be an average of the dose for that subject and the dose given to the most recent previous subject given propofol who reached a BIS value of 50 or below. 4) The latter will be repeated for propofol treated subjects alongside the series of patients receiving test drug until the dose range variations have become small and five or six subjects have achieved a BIS value of 50 or less having received the same dose +/- 10% of propofol. These 6 doses achieving anaesthetic levels of BIS will be combined to calculate the mean ± sem induction dose for comparison with that figure calculated for subjects that received PHAX001.
Control group
Active

Outcomes
Primary outcome [1] 262390 0
speed of induction of anaesthesia to BIS level of 50
Timepoint [1] 262390 0
within 60 seconds of drug injection
Secondary outcome [1] 273688 0
time course of anaesthesia
Timepoint [1] 273688 0
speed of onset and recovery from anaesthesia compared with propofol
Secondary outcome [2] 273689 0
side effects
Timepoint [2] 273689 0
Each subject will receive a single dose of either propofol or PHAX001 administered over a time period of 15 seconds. During this 15 second induction the occurrence and timing of side effects such as pain on injection and abnormal muscle movements will be noted. During the injection of drug and for one hour after the drug injection the effects of the drug on blood pressure and heart rate as well as rate and depth of respiration will be measured. For one hour after awakening sleepiness and confusion will be assessed with Richmond Agitation scale and the digital substitution test. Spontaneous complaints of nausea or occurrence of vomiting will also be recorded during this recovery phase.

Eligibility
Key inclusion criteria
male subject age 20-40 with no significant health problems (ASA classification I)
Minimum age
20 Years
Maximum age
40 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
any disease of the cardiovascular or respiratory system; drug abuse/misuse; taking regular medications; excessive alcohol use; smoking cigarettes/cigars

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)
The trial will be advertised by poster. An initial screening interview will be conducted to exclude subjects who do not fulfil the inclusion and exclusion criteria. The subjects will then have an in-depth interview with an investigator at which time the trial will be explained and the subject information and consent form will be discussed and signed. At this time of enrollment the treatment allocation for that subject will be held secret in a computer and unknown to subject or investigators.

Treatment allocation will be by RANDOMIZATION.COM, the code for which will be stored concealed in a computer and only revealed for a subject by the drug administering anaesthetist just before the study of that individual. This would detail treatment type; PHAX001 or propofol. At that stage and thereafter, the subject, the caring anaesthetist and the observers making measurement will continue to be unaware of drug or dose that the subject received because the drug administering anaesthetist will have access to one of the subjects arms for the intravenous injection and the rest of the subject and all personnel will be screened off from view and no verbal communication will occur between drug administering anaesthetist and subject or other personnel for the duration of the study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation schedule will be obtained from RANDOMIZATION.com. This will allocate PHAX001 or propofol to a particular subject. Thereafter the trial is of Bayesian design, the dose given to an individual will be determined by the response in the last subject given that drug. Dose increments/decrements between treatment will be made progressively smaller to "home in" on the effective dose.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
14/11/2013
Actual
14/11/2013
Date of last participant enrolment
Anticipated
30/01/2014
Actual
6/04/2014
Date of last data collection
Anticipated
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 1865 0
Jessie McPherson Private Hospital - Clayton
Recruitment postcode(s) [1] 7648 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 264738 0
Self funded/Unfunded
Name [1] 264738 0
Country [1] 264738 0
Primary sponsor type
Hospital
Name
Southern Health
Address
246 Clayton road
Clayton
Victoria 3168
Country
Australia
Secondary sponsor category [1] 263863 0
University
Name [1] 263863 0
Monash University
Address [1] 263863 0
Monash University
Victoria 3800
Australia
Country [1] 263863 0
Australia
Other collaborator category [1] 251896 0
University
Name [1] 251896 0
Monash University
Address [1] 251896 0
Monash University
Victoria 3800
Australia
Country [1] 251896 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 266724 0
Southern Health Human Research Ethics Committee A
Ethics committee address [1] 266724 0
Ethics committee country [1] 266724 0
Australia
Date submitted for ethics approval [1] 266724 0
20/12/2010
Approval date [1] 266724 0
05/05/2011
Ethics approval number [1] 266724 0
10372A

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32389 0
A/Prof Colin S Goodchild
Address 32389 0
affiliation Monash Institute of Medical Research

Address: Suite 200, 45 Glenferrie Road, Malvern, Victoria 3144
Country 32389 0
Australia
Phone 32389 0
+61 4 1456 1401
Fax 32389 0
Email 32389 0
cgoodfam@bigpond.net.au
Contact person for public queries
Name 15636 0
C S Goodchild
Address 15636 0
Affiliation: Monash Institute of Medical Research

Address: Suite 200, 45 Glenferrie Road, Malvern, Victoria 3144
Country 15636 0
Australia
Phone 15636 0
+61 0414 561 401
Fax 15636 0
+61 3 9885 1144
Email 15636 0
cgoodfam@bigpond.net.au
Contact person for scientific queries
Name 6564 0
C S Goodchild
Address 6564 0
Affiliation: Monash Institute of Medical Research

Address: Suite 200, 45 Glenferrie Road, Malvern, Victoria 3144
Country 6564 0
Australia
Phone 6564 0
+61 0414 561 401
Fax 6564 0
Email 6564 0
cgoodfam@bigpond.net.au

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
EmbaseA phase 1c trial comparing the efficacy and safety of a new aqueous formulation of alphaxalone with propofol.2015https://dx.doi.org/10.1213/ANE.0000000000000856
N.B. These documents automatically identified may not have been verified by the study sponsor.