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Trial registered on ANZCTR


Registration number
ACTRN12610000668000
Ethics application status
Approved
Date submitted
25/07/2010
Date registered
16/08/2010
Date last updated
7/02/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Is one year mortality and morbidity influenced by anaesthesia after major surgery? A Pilot Study
Scientific title
A prospective, randomised, double blind, safety and efficacy study comparing "light" and "deep" general anaesthesia monitored with the Bispectral Index (BIS) or Spectral Entropy (SE) to investigate whether "light" anaesthesia is associated with lower postoperative mortality than "deep" anaesthesia in patients having major surgery
Secondary ID [1] 252297 0
Nil
Universal Trial Number (UTN)
Trial acronym
Balanced Anesthesia
Linked study record

Health condition
Health condition(s) or problem(s) studied:
The depth of anaesthesia used in major surgery and its impact on postsurgical morbidity and mortality 257812 0
Condition category
Condition code
Anaesthesiology 257982 257982 0 0
Anaesthetics

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention General anaesthesia monitored with bispectral index (BIS) or spectral entropy (SE). Targets in the two groups will be BIS (or SE) 50 and 35. We expect 95% of anaesthesia time to be within 5 units of the target range, and no deviations to be greater than 5 minutes. Maintenance phase will be from ten minutes after induction until switching off volatile or hypnotic at the end of the operation.
Anaesthesia Standard care using standard anaesthetic hypnotics, volatiles, opioids and relaxants, Intravenous (IV) or gas induction and maintenance, continuous BIS or SE monitoring with computerised data logging (ie: propofol, thiopentone, midazolam, isoflurane, sevoflurane, desflurane, all opioids, all Nonsteroidal Antiinflammatory Drugs (NSAIDs), ketamine, paracetamol, all antihypertensives, statins & diabetic medication etc) as per usual care. Blood pressure target range will be set before opening the BIS randomization envelope and anaesthetists will be requested to maintain patients within these parameters as much as possible.
Intervention code [1] 256873 0
Other interventions
Comparator / control treatment
Dose comparison will be made from within the Bispectral index target groups outlined in the intervention. Both the intervention and comparator will be managed as per standard of practice to maintain the targets in the two groups will be BIS (or SE) 50 and 35.
Control group
Dose comparison

Outcomes
Primary outcome [1] 258847 0
Recordings
Pre-operative Charlston co-morbidity score, height, weight, American Society of Anaesthesia Score (ASA),Electrocardiography (ECG), Full Blood Count (FBC), Urea and Electrolytes (U&E), Albumin, Cancer status including Tumour Classification (TNM - Tumour, Nodes, Metastasis).
Peri-operative Electronic record capable of being easily read or manual record with minimum of 5 min recording intervals of BIS/SE, Volatile, Blood Pressure (BP), Heart Rate (HR), Arterial Blood oxygen saturation (Sa02), Temp and all drugs administered, so that mean hypnotic depth and deep hypnotic times can calculated. ECG, FBC, U&E, C-reactive protein (CRP). Review of hospital/ outpatient/General Practitioner (GP) notes and self reporting for evidence of: unscheduled Intensive Care Unit (ICU) admission, post-operative wound infection, pneumonia, Deep Vein Thromobis (DVT), Pulmonary Embolism (PE), Myocardial Infarction (MI), Stroke, sepsis, renal/liver dysfunction, post-operative quality of recovery score, cancer status including TNM.
30 days Death rate, ongoing analgesic or antiemetic requirements, review of hospital/outpatient/GP notes and self reporting for evidence of: post-operative wound infection, pneumonia, DVT, PE, MI, Stroke, sepsis, renal/liver dysfunction, overall patient satisfaction
One Year Death rate, DVT, PE, Stroke, MI, Cancer recurrence, Chronic pain related to surgical site.
Timepoint [1] 258847 0
30 days after randomisation
Secondary outcome [1] 264967 0
Morality and Morbidity review
Timepoint [1] 264967 0
1 year after randomisation

Eligibility
Key inclusion criteria
Age 60 and over, American Society of Anesthesiologists (ASA) Score 3 or 4, major surgery lasting over 2 hours, expected to stay in hospital two or more nights post-operatively, general anaesthesia including with major regional block, anaesthesia duration expected to be over two hours.
Minimum age
60 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Unable to monitor processed Electroencephalography (EEG)(eg most neurosurgery), not expected to survive one year with or without surgery, unable to consent, eg: dementia, , major psychiatric illness, not expected to be contactable one year later, surgery with wake-up test

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)
Participants will be identified by the Anaesthesia Consultant. Allocation will be concealed and treatments assigned by a randomisation envelope
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
randomisation envelopes were done using a minisation algorithm
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
5/07/2010
Actual
5/07/2010
Date of last participant enrolment
Anticipated
Actual
25/05/2012
Date of last data collection
Anticipated
Actual
31/07/2013
Sample size
Target
100
Accrual to date
Final
125
Recruitment in Australia
Recruitment state(s)
WA,VIC
Recruitment postcode(s) [1] 3051 0
3052
Recruitment outside Australia
Country [1] 2782 0
New Zealand
State/province [1] 2782 0
Auckland
Country [2] 2783 0
Hong Kong
State/province [2] 2783 0
sha tin, new territories

Funding & Sponsors
Funding source category [1] 257335 0
Charities/Societies/Foundations
Name [1] 257335 0
Auckland District health Board (ADHB) Research Trust
Country [1] 257335 0
New Zealand
Funding source category [2] 257336 0
Charities/Societies/Foundations
Name [2] 257336 0
Australasian College of Anaesthetists
Country [2] 257336 0
Australia
Primary sponsor type
Individual
Name
Dr Timothy Short
Address
Department of Anaesthesia
Support Building, level 8
Auckland City Hospital
Park Rd
Grafton
Auckland 1023
Country
New Zealand
Secondary sponsor category [1] 256577 0
None
Name [1] 256577 0
Address [1] 256577 0
Country [1] 256577 0
Other collaborator category [1] 251399 0
Charities/Societies/Foundations
Name [1] 251399 0
Australasian College of Anaesthetists
Address [1] 251399 0
ANZCA House
630 St Kilda Road
Melbourne Vic 3004
Country [1] 251399 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 259360 0
Northern X Regional Ethics Committee
Ethics committee address [1] 259360 0
3rd floor, Unisys building
650 Great South Rd
Penrose
Auckland 1061
Ethics committee country [1] 259360 0
New Zealand
Date submitted for ethics approval [1] 259360 0
15/03/2010
Approval date [1] 259360 0
17/05/2010
Ethics approval number [1] 259360 0
NTX/10/04/034

Summary
Brief summary
Recently five overseas studies have found an association between deep anaesthesia and subsequent mortality within one year. There is a need for a large prospective randomised trial of "deep" versus "light" anaesthesia to determine if the relationship is a causal one. This would require the study of about 6000 patients. In this pilot study, 100 patients will be randomised to either "light" or "deep" anaesthesia using the Bispectral Index depth monitor. In all other respects the anaesthesia will be unaltered in choice of anaesthetic drugs or techniques used. We will then follow up all patients for one year to ascertain the incidence of complications of anaesthesia and surgery, cancer recurrence if relevant and survival. The study has the support of the Clinical Trials group of the Australian and New Zealand College of Anaesthetists. If successful, the pilot study will be used as the basis for a large project grant to the Health Research Council in New Zealand (NZ), hopefully combined with an application to the National Health and Medical Research Council in Australia.
Trial website
Trial related presentations / publications
Short TG, Leslie K, Campbell D, Chan MT, Corcoran T,
O’Loughlin E, Frampton C, Myles P. A pilot study for a prospective,
randomized, double-blind trial of the influence
of anesthetic depth on long-term outcome. Anesth Analg
2014;118:981–6
Public notes

Contacts
Principal investigator
Name 31433 0
A/Prof Timothy Short
Address 31433 0
Dept Anaesthesia - Level 8
Auckland City Hospital
Park Rd
Grafton
Auckland 1023
Country 31433 0
New Zealand
Phone 31433 0
+6493757095
Fax 31433 0
Email 31433 0
[email protected]
Contact person for public queries
Name 14680 0
Davina McAllister
Address 14680 0
Department of Anesthesia
Level 8 Support Building
Auckland City Hospital
Park Rd
Grafton
Auckland 1023
Country 14680 0
New Zealand
Phone 14680 0
+6493797440
Fax 14680 0
+6493754378
Email 14680 0
[email protected]
Contact person for scientific queries
Name 5608 0
Dr Timothy Short
Address 5608 0
Department of Anesthesia
Level 8 Support Building
Auckland City Hospital
Park Rd
Grafton
Auckland 1023
Country 5608 0
New Zealand
Phone 5608 0
+6493797440
Fax 5608 0
+6493754378
Email 5608 0
[email protected]

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