Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000548134
Ethics application status
Approved
Date submitted
2/04/2019
Date registered
8/04/2019
Date last updated
10/06/2022
Date data sharing statement initially provided
8/04/2019
Date results information initially provided
8/02/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of sevoflurane versus propofol on cerebral autoregulation during anaesthesia for robot-assisted laparoscopic prostatectomy
Scientific title
A randomized comparison of the effects of Propofol versus Sevoflurane on cerebral autoregulation when conducting general anaesthesia for robot-assisted prostate surgery.
Secondary ID [1] 297803 0
Nil known
Universal Trial Number (UTN)
U1111-1230-6239
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
anaesthesia 312165 0
cerebral autoregulation 312167 0
Condition category
Condition code
Anaesthesiology 310713 310713 0 0
Anaesthetics

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients undergoing robotic prostate surgery will have anaesthesia initiated by Propofol. After initiation, patients will then be randomised to have their anaesthesia maintained using the volatile anaesthetic agent, sevoflurane, or the intravenous agent, propofol.

A Bispectral Index (BIS) monitor will be used to measure the depth of anaesthesia in subjects. The target BIS score is 45 +/- 5. The dosage of Propofol or Sevoflurane will vary between subjects in order to keep the BIS constant. Propofol and Sevoflurane will be constantly administered throughout the operation.
Autoregulation will be tested at hourly intervals, starting before the initiation of the steep Trendelenburg position and every hour thereafter. Autoregulation testing will require the administration of phenylephrine. Phenylephrine will be administered in order to alter Mean Arterial Pressure (MAP) between 80-100 mmHg. This is required in order to test cerebral autoregulation. Cerebral autoregulation will be tested using a TransCranial Doppler (TCD) machine. The TCD will gather blood flow velocity data from the middle cerebral artery, this will be combined with data on MAP to calculate the auto regulation index (ARI).
The intraoperative opioid will be remifentanil, administered by a target-controlled infusion with a targeted effect-site concentration of 2 mcg/mL - 4 mcg/mL.
Intervention code [1] 314044 0
Treatment: Drugs
Comparator / control treatment
Inhalational Sevoflurane
Control group
Active

Outcomes
Primary outcome [1] 319562 0
Cerebral autoregulation will be assessed using a TransCranial Doppler (TCD). This will measure blood flow velocity in the Middle Cerebral Artery (MCA) relative to alterations in Mean Arterial Pressure (MAP). An Autoregulation Index (ARI) will be calculated and cerebral autoregulation will be said to be intact if ARI greater than 0.4 and will be said to not be intact if ARI is equal to or less than 0.4.
Timepoint [1] 319562 0
The last ARI calculated whilst in the Steep Trendelenburg position before returning to the supine position will be used as the primary timepoint to determine whether cerebral autoregulation has been left intact (ARI great than 0.4) or not (ARI less than or equal to 0.4).
Secondary outcome [1] 406035 0
Cerebral autoregulation was assessed at other stages during RALP, including before the initation of the steep Trendelenburg position. This will be assessed via measurement of blood flow velocity in the Middle Cerebral Artery (MCA) relative to alterations in Mean Arterial Pressure (MAP). From this, an Autoregulation Index (ARI) will be calculated and cerebral autoregulation will be said to be intact if ARI greater than 0.4 and will be said to not be intact if ARI is equal to or less than 0.4.
Timepoint [1] 406035 0
Before the imitation of the steep Trendelenburg position, and hourly after steep Trendelenburg positioning (excluding final test of autoregulation)

Eligibility
Key inclusion criteria
Robotic prostatectomy
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
History of cerebral vascular disease
Intracranial pathology
Allergy to Propofol.
Contraindication to Sevoflurane, including malignant hyperthermia or history of severe postoperative nausea and vomiting.

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 induction of anaesthesia will be carried out using Propofol, after which, numbered opaque envelopes containing a random sequence will be opened and used to allocate the anaesthetic agent used to maintain anaesthesia.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permutated block randomisation was used to randomise patients
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other design features
The patient will be blind to group allocation.
The treating anaesthetist and investigator will be aware of the anaesthetic agent during data collection.
Investigators will be blind to the agent at the time of data analysis.
Phase
Phase 4
Type of endpoint/s
Pharmacodynamics
Statistical methods / analysis
The Fisher’s exact test was used to compare the proportion of patients in the final test of cerebral autoregulation who had their autoregulation impaired between the propofol and sevoflurane groups

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
24/05/2019
Actual
24/05/2019
Date of last participant enrolment
Anticipated
1/03/2020
Actual
9/10/2020
Date of last data collection
Anticipated
8/03/2020
Actual
9/10/2020
Sample size
Target
30
Accrual to date
Final
30
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 13510 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 14356 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment postcode(s) [1] 26129 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 310726 0
Hospital
Name [1] 310726 0
Royal Prince Alfred Hospital
Country [1] 310726 0
Australia
Primary sponsor type
Government body
Name
Sydney Local Health District
Address
575 Canterbury Rd, Campsie NSW 2194
Country
Australia
Secondary sponsor category [1] 302232 0
None
Name [1] 302232 0
Address [1] 302232 0
Country [1] 302232 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303000 0
Sydney Local Health District Human Research Ethics Committee (RPAH Zone)
Ethics committee address [1] 303000 0
Level 11, KGV Building Missenden Road
CAMPERDOWN NSW 2050
Ethics committee country [1] 303000 0
Australia
Date submitted for ethics approval [1] 303000 0
18/03/2019
Approval date [1] 303000 0
10/05/2019
Ethics approval number [1] 303000 0

Summary
Brief summary
Currently there is no standard anesthetic agent recommended for robotic pelvic and abdominal surgery. Anaesthetic agents have variable effects on the cerebral vasculature and it has been hypothesized that some may be more suitable for robotic pelvic and abdominal surgery than others. For instance, Sevoflurane, a volatile anesthetic agent, increases cerebral vasodilation and hence decreases vascular resistance. This may impair cerebral autoregulation. Propofol, an intravenous agent, has not been shown to affect cerebral vasodilation.
A feature of robotic surgery is the requirement for carbon dioxide pneumoperitoneum in conjunction with steep head-down positioning. We hypothesise that the cerebrovasodilatory effects of carbon dioxide combined with the potential for oedema from head-down positioning could render the brain particularly susceptible to the vasodilatory effects of volatile anaesthetics, including sevoflurane.
Cerebral oedema is a recognised, although rare, complication of robotic prostate surgery. These are long procedures with the patient in a steep head-down position. Previous studies have shown alterations in cerebral blood flow towards the end of surgery. Therefore, the primary outcome of this study will be the last cerebral autoregulation recording at the end of surgery, with a comparison between patients with their anaesthesia maintained with propofol or sevoflurane
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 92130 0
Dr Tim McCulloch
Address 92130 0
Sydney Local Health District, Post Office Box M30 Missenden Road NSW 2050
Country 92130 0
Australia
Phone 92130 0
+61 2 9515 6111
Fax 92130 0
Email 92130 0
[email protected]
Contact person for public queries
Name 92131 0
Mr Tomas Robertson
Address 92131 0
Sydney Local Health District, Post Office Box M30 Missenden Road Camperdown NSW 2050
Country 92131 0
Australia
Phone 92131 0
+61 448162684
Fax 92131 0
Email 92131 0
[email protected]
Contact person for scientific queries
Name 92132 0
Mr Tomas Robertson
Address 92132 0
Sydney Local Health District, Post Office Box M30 Missenden Road NSW 2050
Country 92132 0
Australia
Phone 92132 0
+61 448162684
Fax 92132 0
Email 92132 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Data will be available which does not allow identification of individuals. This may include recordings of cerebral autoregulation, data collection forms and other non identifiable data.
When will data be available (start and end dates)?
Data will be available immediately after publication and available up to 5 years post publication
Available to whom?
Availability will be available on a case by case basis based on approval from the Sydney Local Health District.
Available for what types of analyses?
For any research purpose
How or where can data be obtained?
Access subject to approval via the Principal Investigator


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
1750Study protocol    377268-(Uploaded-17-11-2021-22-07-33)-Study-related document.docx



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes 15 May 2022 Robertson TJ, McCulloch TJ, Paleolo... [More Details]
Basic resultsNo 377268-(Uploaded-08-06-2022-18-08-10)-Basic results summary.docx
Plain language summaryNo Patients that require the removal of all or part o... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseEffects of sevoflurane versus propofol on cerebral autoregulation during anaesthesia for robot-assisted laparoscopic prostatectomy.2022https://dx.doi.org/10.1177/0310057X211061158
N.B. These documents automatically identified may not have been verified by the study sponsor.