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Trial registered on ANZCTR


Registration number
ACTRN12616001134415
Ethics application status
Approved
Date submitted
18/02/2015
Date registered
19/08/2016
Date last updated
23/05/2024
Date data sharing statement initially provided
21/06/2019
Date results provided
23/05/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
What is the difference in the safety of Ketamine versus Propofol when used to sedate Acute Psychiatric/ Psychotic Patients who require Aeromedical Retrieval?
Scientific title
The Safety of Ketamine versus Propofol in the Sedation of Acute Psychiatric/ Psychotic Patients requiring Aeromedical Retrieval - A Randomised Clinical trial
Secondary ID [1] 285924 0
Nil Known
Universal Trial Number (UTN)
U1111-1165-7911
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Suicidal Ideation 294314 0
Depression 294315 0
Acute Psychosis 294316 0
Schizophrenia 294317 0
Attempted Suicide 294318 0
Post Natal Depression 294319 0
Self Harm 294320 0
Personality Disorder 294321 0
Bipolar Disorder 294322 0
Condition category
Condition code
Mental Health 294151 294151 0 0
Psychosis and personality disorders
Mental Health 294152 294152 0 0
Schizophrenia
Mental Health 294153 294153 0 0
Suicide

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Sedation of acute psychiatric patients requiring aeromedical retrieval with Propofol versus Ketamine.

Protocol for Administration

Richmond Agitation Sedation Scale (RASS) will be utilised to measure sedation level.

Propofol:

The initial dose of Midazolam is determined by the RASS of the patient on arrival of the flight crew at the referral centre; a RASS of >+1, in the absence of premedication with a benzodiazepine,would indicate the need for an initial dose of Midazolam at 0.03mg/kg

Propofol (Target RASS 0 to -3):

(If the patient has not had any benzodiazepine): If Richmond agitation Sedation scale (RASS) >0 start with an initial dose of Midazolam 0.03mg/kg IV
Prepare a Propofol syringe (200mg/20mls)
Deliver ONE bolus of Propofol 0.25mg/kg to aim target RASS
If further sedation required commence Propofol infusion to 0.25mg/kg/hr (approx. 3.5mls/hr)
If RASS +1 increase Propofol infusion by 2mls every 5-10mins until target RASS of 0 to -3 is achieved
If RASS +2 or higher, repeat IV Propofol bolus 0.25mg/kg to acutely reduce agitation
If RASS -5 cease Propofol infusion until target RASS achieved, recommence infusion to maintain target RASS.
For a SBP <90 administer a crystalloid bolus of 250mls
Record the RASS, vital signs, and non-invasive end tidal carbon dioxide (ETCO2) levels every 10 minutes until arrival at receiving centre
There is no maximum dose of Propofol to be administered as the timing of the retrieval cannot be strictly quantified.
Please complete the data collection sheet before filing the patient notes


The intervention period can last between 2-8 hrs. There a number of factors that impact on the duration of intervention; the time of preparing the patient at the referral centre, delay in road ambulance transport to the aircraft, the flight time and delays on road ambulance transport from Darwin International Airport to Royal Darwin Hospital. These factors can only be estimates of time as they vary widely, particularly the ambulance waiting periods from referral centres to the aircraft and from the aircraft to the Royal Darwin hospital.
Intervention code [1] 290900 0
Treatment: Drugs
Comparator / control treatment
Richmond Agitation Sedation Scale (RASS) will be utilised to measure sedation level.

The initial dose of Midazolam is determined by the RASS of the patient on arrival of the flight crew at the referral centre; a RASS of >+1, in the absence of premedication with a benzodiazepine, would indicate the need for an initial dose of Midazolam at 0.05mg/kg

Ketamine (Target RASS 0 to -3):

(If the patient has not had any benzodiazepine): If Richmond Agitation Sedation Scale (RASS) >0 start with an initial dose of Midazolam 0.03mg/kg IV
Prepare a Ketamine (200mg/2ml) syringe by adding 200mg/2ml vial with 20mls Normal Saline (10mg/1ml)
Deliver ONE bolus of Ketamine 1mg/kg as aim target RASS
If further sedation required commence ketamine infusion at 1mg/kg/hr
If RASS +2 or higher, repeat IV ketamine Bolus 0.5mg/kg to acutely reduce agitation rather than increasing infusion rate
If RASS -5 cease ketamine infusion until target RASS achieved, recommence infusion to maintain target RASS
Record the RASS, vital signs, and non-invasive end tidal carbon dioxide (ETCO2) levels every 10 minutes until arrival at receiving centre
For a SBP <90 bolus 250mls of crystalloid
There is no maximum dose of Ketamine stipulated as the timing of the retrieval cannot be strictly quantified
Please complete the data collection sheet before filing the patient notes

The intervention period can last between 2-8 hrs. There a number of factors that impact on the duration of intervention; the time of preparing the patient at the referral centre, delay in road ambulance transport to the aircraft, the flight time and delays in road ambulance transport from Darwin International Airport to Royal Darwin Hospital. These factors can only be estimates of time as they vary widely, particularly the ambulance waiting periods from referral centres to the aircraft and from the aircraft to the Royal Darwin hospital. The patients vital signs (BP, HR, ETCO2, an RASS will be monitored 10 minutely for the entire duration of the retrieval.
Control group
Active

Outcomes
Primary outcome [1] 293945 0
Airway complications - suction, airway adjuncts, manoeuvres/manipulation
These are a composite outcomes.

Flight crews will complete in flight data package which includes a tick box yes or no if any of the above outcomes occur. The Principal investigator will then collate all data into a secure access portal specific to this project.
Timepoint [1] 293945 0
The length of aeromedical retrieval from time of initiation of sedation through to the arrival at the accepting centre (approximately 2-4 hours)
Primary outcome [2] 294457 0
Breathing complications - Oxygen saturations<94% any time during sedation, change in ETCO2>10mmHg or absent CO2 waveform, Respiratory Rate <8 for >10secs during sedation, bag valve mask, stimulation, increase in flow rate of supplemental oxygen

Flight crews will complete in flight data package which includes a tick box yes or no if any of the above outcomes occur. The Principal investigator will then collate all data into a secure access portal specific to this project.
Observations (ETCO2, Oxygen saturation, Heart rate, Respiratory Rate and Blood Pressure will be documented 10 minutely for the duration of care provided by the flight crew.
Timepoint [2] 294457 0
The length of aeromedical retrieval from time of initiation of sedation through to the arrival at the accepting centre (approximately 2-4 hours).
Primary outcome [3] 299310 0
Transfer to a medical ward/ED for pulmonary aspiration post retrieval sedation (respiratory signs and symptoms consistent with pulmonary aspiration that were not present before the sedation and occurred within 12hrs of commencement of sedation timeframe (Bhatt, et al., 2009).

The Principal Investigator will review the participants medical records after admission to the receiving facility.
Timepoint [3] 299310 0
Within 12 hours of the commencement of the sedation protocol
Secondary outcome [1] 313364 0
Number of patients requiring (a) bolus only, (b) bolus and baseline protocol infusion or (c) bolus, base line protocol infusion and increase in protocol infusion rate during transport


Flight crews will complete in flight data package which includes a tick box yes or no if any of the above outcomes occur. The Principal investigator will then collate all data into a secure access portal specific to this project.

The Flight Crew will complete the baseline carbon copy observation chart that includes drug dosing and boluses given throughout the retrieval.
Timepoint [1] 313364 0
The length of aeromedical retrieval from time of initiation of sedation through to the arrival at the accepting centre (approximately 2-4 hours).
Secondary outcome [2] 313365 0
Crew satisfaction with sedation

Flight crews will complete in flight data package which includes a Likert Scale specifying the degree of satisfaction the Flight Doctor had with the study drug administration protocol. The Principal investigator will then collate all data into a secure access portal specific to this project.
Timepoint [2] 313365 0
The length of aeromedical retrieval from time of initiation of sedation through to the arrival at the accepting centre (approximately 2-4 hours).
Secondary outcome [3] 326862 0
(This is a Primary Outcome)
Circulation complications - SBP<90, IV fluid bolus

Flight crews will complete in flight data package which includes a tick box yes or no if any of the above outcomes occur. The Principal investigator will then collate all data into a secure access portal specific to this project.

The Flight Crew will complete the baseline carbon copy observation chart that includes drug dosing and boluses given throughout the retrieval.
Timepoint [3] 326862 0
The length of aeromedical retrieval from time of initiation of sedation through to the arrival at the accepting centre (approximately 2-4 hours).

Eligibility
Key inclusion criteria
All adult acute psychiatric patients requiring aeromedical retrieval
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who known to be in their third trimester of pregnancy will be excluded

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)
Patients will receive standard oral sedation before crew arrival, comprising 10mg Olanzapine and 10mg Diazepam. After tasking of an acute psychiatric patient retrieval, the crew logon to the study database and complete the randomisation eligibility. If it is determined that the patient is 18 years or older, a Flight Nurse and a Flight Doctor (crew) are required for the retrieval then the patient will be considered eligible to be randomised.
will receive and open an envelope at the CareFlight Darwin base with a randomised decision of either Ketamine or Propofol sedation. The need for in-flight sedation will be assessed by the crew on arrival at the referral centre. Prior to sedation, sedation level will be assessed via the Richmond Agitation Sedation Scale (RASS). If the patient is found to have a RASS of +1 to +4, they are deemed to require sedation and they are included in the study. The flight crew will open their envelope at this time which will be randomised to Ketamine or Propofol.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a table created by computer software
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
T-Test
95% Confidence Intervals

Sample size: Soomaroo, Mills, & Ross (2014) had a sample size of 262 patients from one year of data from the same proposed patient population; of the 262 patients forty percent required inflight sedation. All patients retrieved via CareFlight NT are entered into the medical retrieval database. A retrospective analysis of the database identified greater than 720 acute psychiatric patients retrieved from February 2012 – February 2015. Thus it is expected approximately 400 patients who will require inflight sedation will be enrolled in this project over a two year period.


Soomaroo, L., Mills, J., & Ross, M. (2014). Aeromedical Retrieval of Acute Psychiatric Patients. Air Medical Journal, 33(6), 304-308.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
The study was ceased after 4 years as recruiting was slow. To get 400 patients recruited to this study, the study would have needed to continue for at least 8 further years. This was not feasible. Requested to change the status by ANZCTR
Date of first participant enrolment
Anticipated
1/09/2016
Actual
16/09/2016
Date of last participant enrolment
Anticipated
16/09/2020
Actual
2/09/2020
Date of last data collection
Anticipated
1/02/2021
Actual
2/09/2020
Sample size
Target
400
Accrual to date
Final
119
Recruitment in Australia
Recruitment state(s)
NT
Recruitment postcode(s) [1] 9087 0
0820 - Darwin International Airport

Funding & Sponsors
Funding source category [1] 290819 0
Charities/Societies/Foundations
Name [1] 290819 0
Emergency Medicine Foundation
Country [1] 290819 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
CareFlight Limited
Address
12 Lancaster Road
Darwin International Airport
EATON, NT 0812, Australia
Country
Australia
Secondary sponsor category [1] 289202 0
Charities/Societies/Foundations
Name [1] 289202 0
CareFlight New South Wales
Address [1] 289202 0

Locked Bag 2002
Wentworthville NSW 2145
Australia
Country [1] 289202 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292162 0
Human Research Ethics Committee - Menzies School of Health Research
Ethics committee address [1] 292162 0
Ethics committee country [1] 292162 0
Australia
Date submitted for ethics approval [1] 292162 0
21/01/2015
Approval date [1] 292162 0
16/09/2015
Ethics approval number [1] 292162 0
HREC-2015-2375

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

Contacts
Principal investigator
Name 53834 0
Miss Jodie A Mills
Address 53834 0
CareFlight Limited NT
12 Lancaster Road Marrara 0812
Country 53834 0
Australia
Phone 53834 0
+61427275411
Fax 53834 0
Email 53834 0
jodie.mills@careflight.org
Contact person for public queries
Name 53835 0
Jodie A Mills
Address 53835 0
CareFlight Limited NT
12 Lancaster Road Marrara 0812
Country 53835 0
Australia
Phone 53835 0
+61427275411
Fax 53835 0
Email 53835 0
jodie.mills@careflight.org
Contact person for scientific queries
Name 53836 0
Jodie A Mills
Address 53836 0
CareFlight Limited NT
12 Lancaster Road Marrara 0812
Country 53836 0
Australia
Phone 53836 0
+61427275411
Fax 53836 0
Email 53836 0
jodie.mills@careflight.org

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No this data will remain the property of the Northern Territory Government.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Plain language summaryNo Final Updates Between 16th September 2016 and 2... [More Details]

Documents added automatically
No additional documents have been identified.