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Trial registered on ANZCTR


Registration number
ACTRN12617001354370
Ethics application status
Approved
Date submitted
18/09/2017
Date registered
27/09/2017
Date last updated
11/04/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Prevention of early post-operative confusion in older people
Scientific title
Modulation of intra-operative EEG in the elderly to prevent early postoperative delirium
Secondary ID [1] 292911 0
Alpha Max
Universal Trial Number (UTN)
U1111-1202-2584
Trial acronym
Alpha-Max
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Emergence delirium 304762 0
Ageing 304765 0
Condition category
Condition code
Anaesthesiology 304085 304085 0 0
Anaesthetics

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
2 by 2 factorial design
INTERVENTION 1: Active manipulation of volatile anaesthesia and opioid to maximise frontal EEG alpha power. The frontal EEG will be continuously analysed and dose-response curves created during the anaesthetic. These will be used to guide bolus dosing of intravenous fentanyl, an opioid, and to guide the (inhaled) concentration of volatile anaesthesia administered. The bolus doses and maximum and minimum levels will be determined in conjunction with the attending anaesthetist and will be based on previous responses in a dynamic process.

INTERVENTION 2: Conversion from inhaled volatile to propofol (intravenous) anaesthesia for emergence from anaesthesia. The volatile anaesthesia will be ceased at time of skin closure and propofol will be given by a target controlled infusion to an effect site concentration of 3ug/ml for at least 2 minutes and then ceased for emergence from anaesthesia
Intervention code [1] 299138 0
Treatment: Other
Intervention code [2] 299139 0
Treatment: Drugs
Comparator / control treatment
Control 1: Standard anaesthetic care without information regarding alpha power. Typically this is based upon cardiovascular parameters and degree of surgical stimulation as judged by the attending anaesthetist
Control 2: Standard anaesthetic emergence from volatile anaesthesia. The volatile anaesthetic is ceased and high flow oxygen given to purge the circuit once surgery is complete.

Burst suppression alarm will be used on all participants as standard care. One group receives intervention 1, one group receives intervention 2, one group receives both interventions and one group receives no interventions
Control group
Active

Outcomes
Primary outcome [1] 303402 0
Frontal alpha EEG power
Timepoint [1] 303402 0
Maintenance phase (mean)
Primary outcome [2] 303403 0
Frontal EEG alpha power
Timepoint [2] 303403 0
Emergence phase of anaesthesia (mean)
Secondary outcome [1] 338840 0
Emergence delirium using CAM-PACU and NuDesc tools
Timepoint [1] 338840 0
30 minutes post extubation
Secondary outcome [2] 338841 0
EEG emergence trajectory pattern
Timepoint [2] 338841 0
Emergence from anaesthesia
Secondary outcome [3] 338842 0
Postoperative delirium assessed using 3D-CAM tool and the 3D-CAM-S as a marker of the severity of delirium
Timepoint [3] 338842 0
Post-anaesthesia care unit.
Secondary outcome [4] 338843 0
Days alive and out of hospital
Timepoint [4] 338843 0
30 days
Secondary outcome [5] 338844 0
Quality of recovery score - QoR-15
Timepoint [5] 338844 0
Day 1
Secondary outcome [6] 338845 0
Cognitive assessment (Montreal Cognitive Assessment)
Timepoint [6] 338845 0
12 months
Secondary outcome [7] 338846 0
Major adverse events (including mortality) by note review and telephone interview
Timepoint [7] 338846 0
30 day and 12 months
Secondary outcome [8] 338847 0
Length of stay
Timepoint [8] 338847 0
Discharge
Secondary outcome [9] 338944 0
Discharge destination
Timepoint [9] 338944 0
Discharge
Secondary outcome [10] 345365 0
Days alive and out of hospital as a composite secondary outcome assessed by telephone interview and medical records
Timepoint [10] 345365 0
Day 30

Eligibility
Key inclusion criteria
Age > 60 years
Capacity for informed consent
Undergoing non-cardiac, non-intracranial surgery expected to take 2 hours or longer
Minimum age
60 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Inability to consent
Chronic pain
Deemed unsuitable for study protocol by anaesthetic care provider

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)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation) with stratification according to pre-operative cognitive score (MOCA) and surgical type (vascular/orthopaedic/general or other)
Masking / blinding
Blinded (masking 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
Factorial
Other design features
Assessment of feasibility of real time EEG management based of spectral EEG features
Simultaneous collection of 64 channel EEG data for observational work
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
To achieve statistical significance for a reduction in delirium from 16% to 8% requires 516 patients for the secondary endpoint of delirium (two-tailed alpha 0.05, beta 0.8, chi-squared test). We aim to recruit 600 patients to account for dropouts, uncertainty regarding the predicted incidence of delirium in the study population with our protocol and to detect slightly smaller reductions in delirium, which would still be clinically significant . We anticipate we will be overpowered for the primary endpoints of alpha power; it is unknown what constitutes a clinically important difference in the observed alpha oscillation - this study aims to determine this and whether it is subject to pharmacological manipulation during general anaesthesia

Recruitment
Recruitment status
Recruiting
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 outside Australia
Country [1] 9216 0
New Zealand
State/province [1] 9216 0
Waikato
Country [2] 9217 0
United States of America
State/province [2] 9217 0
Georgia
Country [3] 9218 0
Germany
State/province [3] 9218 0
Munich

Funding & Sponsors
Funding source category [1] 297540 0
University
Name [1] 297540 0
University of Auckland , Shrimpton Fund
Address [1] 297540 0
Department of Anaesthesiology
Faculty of Medical and Health Sciences
University of Auckland
Auckland 1142
Private Bag 92019
Country [1] 297540 0
New Zealand
Funding source category [2] 297542 0
Charities/Societies/Foundations
Name [2] 297542 0
James S McDonnell Foundation
Address [2] 297542 0
1034 S Brentwood Blvd, St. Louis, MO 63117, USA
Country [2] 297542 0
United States of America
Primary sponsor type
University
Name
University of Auckland
Address
Department of Anaesthesiology
Faculty of Medical and Health Sciences
University of Auckland
Auckland 1142
Private Bag 92019
Country
New Zealand
Secondary sponsor category [1] 296552 0
Hospital
Name [1] 296552 0
Waikato Hospital
Address [1] 296552 0
Corner Selwyn Pembroke St
Hamilton 3240
Country [1] 296552 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298636 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 298636 0
Health and Disability Ethics Committees
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 298636 0
New Zealand
Date submitted for ethics approval [1] 298636 0
Approval date [1] 298636 0
01/06/2017
Ethics approval number [1] 298636 0
17/NTA/56

Summary
Brief summary
Emergence delirium is a distressing complication of surgery and anaesthesia which is common in the elderly population. It is associated with increased morbidity, mortality, hospital length of stay, discharge to residential care and future cognitive decline. From our previous work we have observed that emergence delirium seems to occur less frequency when alpha activity measured from frontal EEG lead is strong and maintained during emergence from anaesthesia.
We plan to conduct a 2 by 2 factorial study to assess the efficacy of 2 interventions which we hope may prevent emergence delirium. Intervention 1 is the use of real-time frontal analysis and anaesthetic and opioid levels to guide anaesthesia to optimise alpha activity. Intervention 2 is the conversion from volatile (gas-based) anaesthesia to propofol anaesthesia for the emergence (waking) phase of anaesthesia. We aim to determine if these interventions are successful in improving the observed alpha activity and subsequently reduce the incidence of emergence delirium in this high risk population
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 77726 0
Dr Amy Gaskell
Address 77726 0
Dept of Anaesthesia
Waikato Hospital
Corner Pembroke Selwyn St
Hamiton 3240
Country 77726 0
New Zealand
Phone 77726 0
+64 7 839 8899
Fax 77726 0
Email 77726 0
amy.gaskell@waikatodhb.health.nz
Contact person for public queries
Name 77727 0
Dr Amy Gaskell
Address 77727 0
Dept of Anaesthesia
Waikato Hospital
Corner Pembroke Selwyn St
Hamiton 3240
Country 77727 0
New Zealand
Phone 77727 0
+64 7 839 8899
Fax 77727 0
Email 77727 0
amy.gaskell@waikatodhb.health.nz
Contact person for scientific queries
Name 77728 0
Dr Amy Gaskell
Address 77728 0
Dept of Anaesthesia
Waikato Hospital
Corner Pembroke Selwyn St
Hamiton 3240
Country 77728 0
New Zealand
Phone 77728 0
+64 7 839 8899
Fax 77728 0
Email 77728 0
amy.gaskell@waikaotdhb.health.nz

No data has been provided for results reporting
Summary results
Not applicable