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Trial registered on ANZCTR


Registration number
ACTRN12612000632897
Ethics application status
Approved
Date submitted
8/06/2012
Date registered
13/06/2012
Date last updated
11/06/2021
Date data sharing statement initially provided
4/02/2020
Date results provided
4/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
The Influence of Anaesthetic Depth on Patient Outcome after Major Surgery
Scientific title
A prospective, randomised, double-blind, active control, parallel assessment, intention to treat, safety and efficacy study comparing "light" and "deep" general anesthesia monitored with Bispectral Index (BIS) to investigate whether depth of anesthesia alters peri-operative outcomes in patients having major surgery
Secondary ID [1] 280655 0
None
Universal Trial Number (UTN)
Trial acronym
BALANCED
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Perioperative Outcomes 286661 0
Condition category
Condition code
Anaesthesiology 286955 286955 0 0
Other anaesthesiology

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
General anaesthesia monitored with Bispectral Index (BIS). BIS targets will be either 50 or 35. We expect 90% of anaesthesia time to be within 5 units of the target range and no deviations for >5 minutes. Anaesthesia standard care using standard anaesthetic hypnotics, volatiles, opioids and relaxants, intravenous or inhalational gas induction, volatile maintenance, continuous BIS monitoring, computerised data logging of BIS, blood pressure and volatile anaesthetic concentration. An individualised blood pressure target range appropriate for the patient being studied will be set by the anaesthetist before BIS target randomization
Intervention code [1] 285044 0
Treatment: Other
Intervention code [2] 285062 0
Early detection / Screening
Intervention code [3] 285063 0
Treatment: Drugs
Comparator / control treatment
Comparison between BIS target of 50 and 35 will be the comparable treatment
Control group
Dose comparison

Outcomes
Primary outcome [1] 287299 0
One-year mortality. One year mortality will be compared between randomised groups using a Mantel-Haenszel Chi-square test, stratified on study centre.
A two-tailed p-value <0.049 will be taken to indicate statistical significance.
One year mortality is expected to be approximately 10% based on the findings of Leslie's study and Australasian studies. The reduction in mortality in the light anaesthesia group is expected to be 20%.
A power analysis using p1=0.10 and p2=0.08 indicates that N=3250 patients are required in each group, Beta=0.8,alpha=0.049. The alpha level is reduced to allow for the single interim analysis.
Timepoint [1] 287299 0
one year after randomisation
Secondary outcome [1] 297858 0
Morbidity review for the presence of myocardial infarction (MI), cardiac arrest, pulmonary embolism (PE), stroke, sepsis, surgical site infection, Intensive Care Unit (ICU) stay, hospital stay, awareness, WHODAS disability score, disability free survival, persistent postoperative pain and cancer recurrence will be compared between randomized groups using Mantel-Haenszel chi-square tests or Fisher's exact test depending on the expected cell frequencies. Additionally a composite score including the presence of any of MI, cardiac arrest, stroke, PE, sepsis, surgical site infection, post-operative delirium and cognitive decline, will be compared between randomised groups also using a chi-square test. Additional analyses will also explore the role of MI, cardiac arrest, stroke, PE, sepsis, surgical site infection post-operative delirium and cognitive decline on one year mortality using Cox's proportional hazards regression to develop a model of independent predictors of one year mortality. In the New Zealand cohort, an exploratory analysis using DAOH will explore the relationship between this composite outcome and long-term mortality.The randomized group will be added to this model to assist explanation of any observed differences in outcome between the randomized groups. This change was made during recruitment as a consented sub-study. The NZ DAOH observational review was added at the end of the study to explore the relationship between long-term mortality and study outcomes.
Timepoint [1] 297858 0
30 days, 90 days, one year and long term (up to 8 years) following randomisation
This change was made during recruitment as a consented sub-study. The NZ DAOH observational review was added at the end of the study to explore the relationship between long-term mortality and study outcomes.

Eligibility
Key inclusion criteria
Age equal to/greater than 60 years, ASA grade 3 or 4, surgery expected to last >2 hours, post-operative hospital stay expected to be 2 or more nights, general anaesthesia with or without major regional block.
Minimum age
60 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Unable to monitor BIS (eg cranial or intracranial surgery), not expected to survive one year, unable to consent, not expected to be contactable in one year, 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)
Patients who are eligible for the trial will be identified by a consultant anesthetist and given the trial information sheet by a member of the research team and encouraged to discuss the study with their family or whanau before written informed consent is sought.
Treatment allocation
Once all entry details are given and eligibility confirmed, the patient will be randomised by contacting the automated central telephone randomisation service. Allocation will be concealed from subjects, investigators and outcome assessors. Only the anesthetist conducting the anesthesia will be aware of the treatment allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table generated by a computer software - sequence. Assignment to one of the two groups will be stratified for collaborating centre and a unique study number given.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/10/2012
Actual
19/12/2012
Date of last participant enrolment
Anticipated
30/11/2017
Actual
12/12/2017
Date of last data collection
Anticipated
30/03/2018
Actual
31/01/2018
Sample size
Target
6500
Accrual to date
Final
6649
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 1059 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 1060 0
St Vincents Private Hospital Lismore - Lismore
Recruitment hospital [3] 1061 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [4] 1062 0
The Alfred - Prahran
Recruitment hospital [5] 1063 0
Western Hospital - Henley Beach
Recruitment hospital [6] 1064 0
Royal Perth Hospital - Perth
Recruitment hospital [7] 1065 0
Fremantle Hospital and Health Service - Fremantle
Recruitment hospital [8] 6072 0
Prince of Wales Hospital - Randwick
Recruitment hospital [9] 6073 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [10] 6074 0
Peter MacCallum Cancer Institute - East Melbourne
Recruitment hospital [11] 6075 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [12] 6076 0
Westmead Hospital - Westmead
Recruitment hospital [13] 6077 0
St John of God Hospital, Ballarat - Ballarat
Recruitment hospital [14] 6078 0
St John of God Hospital, Subiaco - Subiaco
Recruitment hospital [15] 6079 0
Royal Hobart Hospital - Hobart
Recruitment hospital [16] 6080 0
Liverpool Hospital - Liverpool
Recruitment hospital [17] 6081 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [18] 6082 0
King Edward Memorial Hospital - Subiaco
Recruitment hospital [19] 6083 0
The Canberra Hospital - Garran
Recruitment hospital [20] 6084 0
Epworth Richmond - Richmond
Recruitment hospital [21] 6085 0
Nambour General Hospital - Nambour
Recruitment hospital [22] 6086 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [23] 6087 0
Fiona Stanley Hospital - Murdoch
Recruitment outside Australia
Country [1] 4357 0
New Zealand
State/province [1] 4357 0
Country [2] 5116 0
Hong Kong
State/province [2] 5116 0
Shantin, New Territories
Country [3] 7993 0
United States of America
State/province [3] 7993 0
Texas
Country [4] 7994 0
United States of America
State/province [4] 7994 0
New York
Country [5] 7995 0
United States of America
State/province [5] 7995 0
Ohio
Country [6] 7996 0
United States of America
State/province [6] 7996 0
North Carolina
Country [7] 7997 0
United Kingdom
State/province [7] 7997 0
Country [8] 7998 0
Netherlands
State/province [8] 7998 0

Funding & Sponsors
Funding source category [1] 285411 0
Government body
Name [1] 285411 0
Health Research Council of new Zealand
Country [1] 285411 0
New Zealand
Funding source category [2] 287364 0
Government body
Name [2] 287364 0
National Health and Medical Research Council
Country [2] 287364 0
Australia
Primary sponsor type
Individual
Name
Assoc Professor Dr Timothy Short
Address
Department of Anaesthesia
Level 8, Support Building
Auckland City Hospital
Park Rd
Grafton
Auckland 1023
Country
New Zealand
Secondary sponsor category [1] 292794 0
None
Name [1] 292794 0
Address [1] 292794 0
none
Country [1] 292794 0
Other collaborator category [1] 276856 0
Other Collaborative groups
Name [1] 276856 0
Australia New Zealand College of Anaesthetist Clinical Trials Group
Address [1] 276856 0
ANZCA House
630 St Kilda Road
Melbourne Vic 3004
Country [1] 276856 0
Australia
Other collaborator category [2] 277437 0
University
Name [2] 277437 0
Monash University
Address [2] 277437 0
School of Public Health and Preventive Medicine
The Alfred Centre
99 Commercial Road
Melbourne Vic 3004
Country [2] 277437 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287425 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 287425 0
Ethics committee country [1] 287425 0
New Zealand
Date submitted for ethics approval [1] 287425 0
11/06/2012
Approval date [1] 287425 0
03/09/2012
Ethics approval number [1] 287425 0
12/NTA/16
Ethics committee name [2] 295395 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [2] 295395 0
Ethics committee country [2] 295395 0
Australia
Date submitted for ethics approval [2] 295395 0
Approval date [2] 295395 0
18/03/2013
Ethics approval number [2] 295395 0
HREC/12/MH/385

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 2206 2206 0 0
/AnzctrAttachments/362612-BALANCED_SAP_Final October 2017.pdf (Other)

Contacts
Principal investigator
Name 34290 0
A/Prof Timothy Short
Address 34290 0
Dept Adult and Trauma Anaesthesia
Level 8, Support Building
Auckland City Hospital
2 Park Road
Grafton
Auckland 1023
Country 34290 0
New Zealand
Phone 34290 0
+64 9 3074949 extn 25720
Fax 34290 0
+64 9 3754378
Email 34290 0
tims@adhb.govt.nz
Contact person for public queries
Name 17537 0
Davina McAllister
Address 17537 0
Anaesthesia Research
Department of Anaesthesia and Perioperative Medicine
Level 8, Support Building
Auckland City Hospital
Park Rd
Grafton
Auckland 1023
Country 17537 0
New Zealand
Phone 17537 0
+6493757095
Fax 17537 0
+6493754378
Email 17537 0
davinams@adhb.govt.nz
Contact person for scientific queries
Name 8465 0
Timothy Short
Address 8465 0
Anaesthesia Research
Department of Anaesthesia and Perioperative Medicine
Level 8, Support Building
Auckland City Hospital
Park Rd
Grafton
Auckland 1023
Country 8465 0
New Zealand
Phone 8465 0
+6493670000
Fax 8465 0
+6493754378
Email 8465 0
tims@adhb.govt.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseDelirium and cognitive decline after surgery: A randomised controlled trial of anaesthetic management to improve postoperative mental health outcome.2014
EmbaseRationale and design of the balanced anesthesia study: A prospective randomized clinical trial of two levels of anesthetic depth on patient outcome after major surgery.2015https://dx.doi.org/10.1213/ANE.0000000000000797
EmbaseAnaesthetic implications of mild cognitive impairment.2016https://dx.doi.org/10.1177/0310057x1604400527
EmbaseAnesthetic depth and long-term survival: an update.2016https://dx.doi.org/10.1007/s12630-015-0490-0
EmbaseIn reply.2016https://dx.doi.org/10.1097/ALN.0000000000001206
EmbaseA pilot study using preoperative cerebral tissue oxygen saturation to stratify cardiovascular risk in major non-cardiac surgery.2017https://dx.doi.org/10.1177/0310057x1704500210
EmbaseDeep anesthesia: too much of a good thing?.2017https://dx.doi.org/10.1007/s12630-017-0871-7
Dimensions AIEffect of anesthesia depth on postoperative clinical outcome in patients with supratentorial tumor (DEPTH): study protocol for a randomized controlled trial2017https://doi.org/10.1136/bmjopen-2017-016521
EmbaseAnaesthetic depth and complications after major surgery: an international, randomised controlled trial.2019https://dx.doi.org/10.1016/S0140-6736%2819%2932315-3
Dimensions AIAnaesthetic depth and delirium after major surgery: a randomised clinical trial2021https://doi.org/10.1016/j.bja.2021.07.021
N.B. These documents automatically identified may not have been verified by the study sponsor.