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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04965324




Registration number
NCT04965324
Ethics application status
Date submitted
7/07/2021
Date registered
16/07/2021
Date last updated
23/07/2021

Titles & IDs
Public title
Depth of Anaesthesia and Long-term Survival: The Balanced Anaesthesia Follow-up Study
Scientific title
Depth of Anaesthesia and Long-term Survival in Elderly Surgical Patients: The Balanced Anaesthesia Study Long-term Follow-up Study
Secondary ID [1] 0 0
ACTRN12612000632897
Secondary ID [2] 0 0
A+9283
Universal Trial Number (UTN)
Trial acronym
BALANCEDLT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post-Operative Confusion 0 0
Long Term Adverse Effects 0 0
Surgery--Complications 0 0
Cognitive Dysfunction, Postoperative 0 0
Condition category
Condition code
Neurological 0 0 0 0
Other neurological disorders
Mental Health 0 0 0 0
Other mental health disorders
Public Health 0 0 0 0
Other public health
Surgery 0 0 0 0
Other surgery

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Anaesthesia Depth BIS 35 - BIS 35

Anaesthesia Depth BIS 50 - BIS 50
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Survival
Timepoint [1] 0 0
Between one year and eight years after randomization to the BALANCED Trial

Eligibility
Key inclusion criteria
Inclusion and exclusion criteria will be the same as the Balanced trial with participants limited to those sites described above. Survival data will be censored at date of accessing mortality database.

Inclusion

1. Age over 60 years and over
2. ASA physical status 3 or 4
3. Surgery expected to last over 2 hours
4. Hospital length of stay expected to be 2 nights or more
5. General anaesthesia with or without major regional block
6. Able to monitor BIS throughout anaesthesia
Minimum age
60 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion

1. Unable to monitor BIS
2. Unable to consent
3. Surgery with 'wake up' test
4. Propofol infusion for part or all of maintenance of anaesthesia
5. Previous enrolment in Balanced study

Exclusion The intention-to-treat (ITT) population is defined as all randomised participants who met the inclusion and exclusion criteria who had surgery.

The per-protocol (PP) population is defined as all randomised participants in the study who meet all the inclusion/exclusion criteria for BALANCED with BIS group classified according to the actual median BIS value achieved irrespective of randomisation.

Participants were allocated to the BIS=50 group if the achieved median BIS is between 45 and 55 inclusive, and to the BIS=35 group if the achieved median BIS is between 30 and 40 inclusive. Participants who are not within these ranges will be excluded from these analyses.

Study design
Purpose
Duration
Selection
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/12/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/05/2021
Sample size
Target
Accrual to date
Final
6644
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Government body
Name
Auckland City Hospital
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Health Research Council, New Zealand
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Australian and New Zealand College of Anaesthetists
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Anaesthetic depth and complications after major surgery: an international, randomised controlled trial - The BALANCED trial.

In this large, international, randomised controlled trial that enrolled patients aged 60 years and over with significant comorbidity and at increased risk of complications after major surgery, we found no evidence that light general anaesthesia (bispectral index 50) was superior to deep general anaesthesia (bispectral index 35) in reducing 1-year mortality. The BALANCED long term follow up study will look at whether depth of anesthesia affects long term (beyond 1 year) survival.

The primary hypothesis is that targetting BIS 50 will result in superior long term survival compared to targetting BIS 35.

The two secondary hypotheses are that BIS titration to BIS 50 will

1. reduce local cancer recurrence or metastatic spread and consequently improve long-term survival
2. reduce postoperative delirium and associated cognitive impairment and consequently improve long-term survival

Both these mechanisms would be expected to take longer to manifest as reduced survival than 1-year all-cause mortality primary outcome in the Balanced trial. Trials of cancer outcomes often use 5-year survival or similar timeframes to determine evidence of clinical benefit. A steeper cognitive trajectory due to intermediate outcomes such as delirium and cognitive impairment may take longer than 1 year to produce a clinically important difference in survival 30. The 10.6% relative risk reduction seen in the Balanced trial could translate to a statistically and clinically meaningful survival difference in this high-risk population. This population may have 5-year survival of \~80% translating to an absolute survival difference of \~2% potentially (if the \~10% RRR is maintained beyond 1 year). The alternative is that there is no long-term mortality difference which would provide continuing clinical guidance of the safety of current practice in patients who are not at high risk of delirium. This study could provide a rationale for trials in larger populations (such as the total Balanced trial population) or targeted subgroups such as cancer and delirium to provide further mechanistic insights.

Long-term survival is an important patient-centred outcome. The mechanisms described above may manifest in longer-term outcomes providing a clear rationale for the current trial.
Trial website
https://clinicaltrials.gov/study/NCT04965324
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Timothy Dr Short
Address 0 0
Auckland City Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04965324