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Trial registered on ANZCTR


Registration number
ACTRN12616000085471
Ethics application status
Approved
Date submitted
17/12/2015
Date registered
27/01/2016
Date last updated
4/06/2019
Date data sharing statement initially provided
6/03/2019
Date results information initially provided
6/03/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Comparison of upper airway properties during dexmedetomidine and propofol sedation
Scientific title
Comparison of upper airway properties during light and deep levels of dexmedetomidine and propofol sedation in healthy individuals
Secondary ID [1] 287742 0
ANZCA 16/030
Universal Trial Number (UTN)
U1111-1175-8788
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
anaesthesia safety 296609 0
Condition category
Condition code
Anaesthesiology 296848 296848 0 0
Other anaesthesiology

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A randomised cross over study design will be employed. 20 healthy volunteers will participate in two daytime anaesthesia studies during which they will receive light or deep sedation with intravenous dexmedetomidine or propofol in randomized order on two separate days. Study days are separated by at least 1 week. Airway collapsibility (pharyngeal critical pressure; Pcrit and pharyngeal closing pressure; Pclose), neuromuscular responsiveness derived from genioglossus EMG (EMGgg), and sedation depth (Observer’s Assessment of Alertness/Sedation (OAAS) Scale, Richmond Agitation Sedation Scale (RASS), University of Michigan Sedation Scale (UMSS) and processed EEG/EMG (Bispectral Index Score; BIS)) will be assessed at light and deep levels of sedation. Pclose will also be assessed at 2 minute intervals following cessation of drug infusion. EEG (O1,C3,F3,M2), End-tidal CO2 (EtCO2), transcutaneous CO2 (TcCO2) and oesophageal pressure (Pes) will be monitored continuously.

Drug dosing involves a bolus dose (10 minutes at 0,6 microg/kg (DEX) or 4,5 mg/kg/h (= 75 microg/kg/min)(Propofol)) followed by a maintenance infusion aiming for light sedation (DEX: 0,5 microg/kg/h; Propofol 2,5 mg/kg/h (= 42 microg/kg/min)) then deep sedation (DEX: 1,5 microg/kg/h; Propofol 5 mg/kg/h (= 83 microg/kg/min)). At each level of sedation 20 mins is allowed for attainment of steady state prior to beginning measurements. Venous blood samples will be collected at baseline and completion of measurements at light and deep sedation levels for determining drug plasma concentrations. The first measurement will be made at completion of the 30min bolus/steady state period and sedation will not extend beyond 75 mins from the time of the start of the first measurement.
Intervention code [1] 293138 0
Treatment: Drugs
Comparator / control treatment
Propofol: drug dosing involves a bolus dose (10 minutes at 4,5 mg/kg/h (= 75 microg/kg/min)) followed by a maintenance infusion aiming for light sedation (2,5 mg/kg/h (= 42 microg/kg/min)) then deep sedation (5 mg/kg/h (= 83 microg/kg/min)). At each level of sedation 20 mins is allowed for attainment of steady state prior to beginning measurements. Venous blood samples will be collected at baseline and completion of measurements at light and deep sedation levels for determining drug plasma concentrations. The first measurement will be made at completion of the 30min bolus/steady state period and sedation will not extend beyond 75 mins from the time of the start of the first measurement.
Control group
Active

Outcomes
Primary outcome [1] 296456 0
Airway collapsibility 1. pharyngeal critical pressure technique (Pcrit) where applied nasal pressure is lowered during early expiration for 5 breaths to a pressure eliciting flow limitation and then returned to the holding pressure. Following a recovery period to allow all physiological measurements to stabilise nasal pressure is again lowered to induce a different degree of flow limitation. A minimum of three pressure reductions inducing variable degrees of flow limitation (identified from no further increase in flow despite 3cmH2O increase in negative pressure as assessed by Pes) are required to produce a single Pcrit measurement from the relationship between airflow and pressure. Pcrit is the pressure at which flow would be zero. Any breaths associated with arousal or variations in sleep stage are excluded. 2. airway collapsing pressure (Pclose) technique where airflow is abruptly occluded with a pneumatic balloon valve for a maximum of 5 inspiratory efforts. The mask pressure (Pmask) at which the point of divergence between Pmask and Pes the Pclose. Note that if there is any degree of mask leak Pclose is unable to be determined, although the measurement of Pcrit is possible and remains the gold standard method of assessing upper airway collapsibility. The measurement of Pclose was unable to be performed in the majority of participants.
Timepoint [1] 296456 0
At the completion of the 20 minute stabilisation period during both light and deep sedation. Pcrit is performed first followed by 3 Pcloses.
Secondary outcome [1] 318487 0
neuromuscular responsiveness (genioglossus EMG; EMGgg), phasic and tonic EMGgg
Timepoint [1] 318487 0
At the completion of the 20 minute stabilisation period during assessments of pcrit (pressure reductions) during both light and deep sedation.
Secondary outcome [2] 319828 0
arousability (sedation depth), OASS, RASS, UMSS
Timepoint [2] 319828 0
At the completion of the assessments of airway collapsibility during both light and deep sedation
Secondary outcome [3] 319830 0
Apneas, mean frequency and duration as identified from the pneumotach-dervied airflow signal will be reported.
Timepoint [3] 319830 0
At any time during drug infusion
Secondary outcome [4] 320193 0
Bispectral Index (BIS), mean, maximum and minimum values
Timepoint [4] 320193 0
From the completion of the 20 minute stabilisation period during assessments of pcrit, pclose and arousal assessment during both light and deep sedation.

Eligibility
Key inclusion criteria
healthy volunteers
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
known cardiovascular or respiratory disease
uncontrolled hypertension or diabetes
current smoking
BMI >37kg/m2
history of hypotension, bradycardia, kidney/liver impairment
pregnancy
elevated anaesthesia risk

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 4
Type of endpoint(s)
Safety
Statistical methods / analysis
Two-way repeated measures analysis of variance (ANOVA) will be utilised to determine whether, for a given level of sedation, upper airway collapsibility differs during light and deep dexmedetomidine and propofol sedation
Since we do not have any data on dexmedetomidine on upper airway collapsibility a proper power analysis was not possible to make. Therefore, after 10 completed patients and interims analysis will be done and power will be recalculated.

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)
WA
Recruitment hospital [1] 4512 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 12118 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 292285 0
Charities/Societies/Foundations
Name [1] 292285 0
Australian and New Zealand College of Anaesthestists
Address [1] 292285 0
Australian and New Zealand College of Anaesthetists
ANZCA House,
630 St Kilda Road,
Melbourne, Victoria 3004,
Australia.
Country [1] 292285 0
Australia
Primary sponsor type
Hospital
Name
Sir Charles Gairdner Hospital
Address
Hospital Avenue,
Nedlands
WA 6009
Country
Australia
Secondary sponsor category [1] 290969 0
Hospital
Name [1] 290969 0
Karolinska University Hospital
Address [1] 290969 0
Karolinska University Hospital, Solna
SE-171 76 Stockholm
Sweden
Country [1] 290969 0
Sweden

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293758 0
Sir Charles Gairdner Hospital
Ethics committee address [1] 293758 0
Hospital Avenue
Nedlands
WA 6009
Ethics committee country [1] 293758 0
Australia
Date submitted for ethics approval [1] 293758 0
29/06/2015
Approval date [1] 293758 0
21/07/2015
Ethics approval number [1] 293758 0
2009-037

Summary
Brief summary
Dexmedetomidine is increasingly used for procedural and intensive care unit sedation. This growing popularity is based on the belief that it has relatively little impact on both ventilatory drive and upper airway collapsibility, in contrast to benzodiazepines and propofol, which are known to depress ventilation and predispose to upper airway obstruction. However, we have preliminary data demonstrating that, at similar levels of sedation, the degree of upper airway collapsibility observed with dexmedetomidine is similar to that with propofol. Formal evaluation is now required. This study will compare the effects of dexmedetomidine and propofol on upper airway function in healthy people. Information gained from this study will improve our understanding of the effects of dexmedetomidine and its safe use for procedural and intensive care unit sedation

Aim:
To compare the degree of upper airway collapsibility and mechanisms underlying it during light and deep levels of dexmedetomidine and propofol sedation in healthy individuals

Hypothesis:
Upper airway collapsibility will increase with increasing depth of sedation but will be similar at comparable depths of dexmedetomidine and propofol sedation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 61198 0
Dr Jennifer Walsh
Address 61198 0
Department of pulmonary physiology and sleep medicine
QEII Medical Centre
Internal mailbox 201
Hospital Avenue
Nedlands
WA 6009
Country 61198 0
Australia
Phone 61198 0
+61 8 9346 1070
Fax 61198 0
Email 61198 0
Jennifer.walsh@health.wa.gov.au
Contact person for public queries
Name 61199 0
Dr Jennifer Walsh
Address 61199 0
Department of pulmonary physiology and sleep medicine
QEII Medical Centre
Internal mailbox 201
Hospital Avenue
Nedlands
WA 6009
Country 61199 0
Australia
Phone 61199 0
+61 8 9346 1070
Fax 61199 0
Email 61199 0
Jennifer.walsh@health.wa.gov.au
Contact person for scientific queries
Name 61200 0
Dr Jennifer Walsh
Address 61200 0
Department of pulmonary physiology and sleep medicine
QEII Medical Centre
Internal mailbox 201
Hospital Avenue
Nedlands
WA 6009
Country 61200 0
Australia
Phone 61200 0
+61 8 9346 1070
Fax 61200 0
Email 61200 0
Jennifer.walsh@health.wa.gov.au

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?
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary