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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

5/05/2023

Date data sharing statement initially provided

15/03/2019

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]

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

Ageing

Condition category

Condition code

Anaesthesiology

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]

Treatment: Other

Intervention code [2]

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]

Frontal alpha EEG power

Timepoint [1]

Maintenance phase (mean)

Primary outcome [2]

Frontal EEG alpha power

Timepoint [2]

Emergence phase of anaesthesia (mean)

Secondary outcome [1]

Emergence delirium using CAM-PACU and NuDesc tools

Timepoint [1]

30 minutes post extubation

Secondary outcome [2]

EEG emergence trajectory pattern

Timepoint [2]

Emergence from anaesthesia

Secondary outcome [3]

Postoperative delirium assessed using 3D-CAM tool and the 3D-CAM-S as a marker of the severity of delirium

Timepoint [3]

Post-anaesthesia care unit.

Secondary outcome [4]

Days alive and out of hospital

Timepoint [4]

30 days

Secondary outcome [5]

Quality of recovery score - QoR-15

Timepoint [5]

Day 1

Secondary outcome [6]

Cognitive assessment (Montreal Cognitive Assessment)

Timepoint [6]

12 months

Secondary outcome [7]

Major adverse events (including mortality) by note review and telephone interview

Timepoint [7]

30 day and 12 months

Secondary outcome [8]

Length of stay

Timepoint [8]

Discharge

Secondary outcome [9]

Discharge destination

Timepoint [9]

Discharge

Secondary outcome [10]

Days alive and out of hospital as a composite secondary outcome assessed by telephone interview and medical records

Timepoint [10]

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

Sex

Both males and females

Can healthy volunteers participate?

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

Stopped early

Data analysis

Data collected is being analysed

Reason for early stopping/withdrawal

Lack of funding/staff/facilities
Other reasons/comments

Other reasons

Original sites not able to conduct study

Date of first participant enrolment

Anticipated

27/11/2017

Actual

15/02/2018

Date of last participant enrolment

Anticipated

5/10/2020

Actual

2/09/2020

Date of last data collection

Anticipated

4/10/2021

Actual

4/10/2021

Sample size

Target

600

Accrual to date

Final

200

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Waikato

Funding & Sponsors

Funding source category [1]

University

Name [1]

University of Auckland , Shrimpton Fund

Address [1]

Department of Anaesthesiology
Faculty of Medical and Health Sciences
University of Auckland
Auckland 1142
Private Bag 92019

Country [1]

New Zealand

Funding source category [2]

Charities/Societies/Foundations

Name [2]

James S McDonnell Foundation

Address [2]

1034 S Brentwood Blvd, St. Louis, MO 63117, USA

Country [2]

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]

Hospital

Name [1]

Waikato Hospital

Address [1]

Corner Selwyn Pembroke St
Hamilton 3240

Country [1]

New Zealand

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Northern A Health and Disability Ethics Committee

Ethics committee address [1]

Health and Disability Ethics Committees
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington
6011

Ethics committee country [1]

New Zealand

Date submitted for ethics approval [1]

Approval date [1]

01/06/2017

Ethics approval number [1]

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

Dr Amy Gaskell

Address

Dept of Anaesthesia
Waikato Hospital
Corner Pembroke Selwyn St
Hamiton 3240

Country

New Zealand

Phone

+64 7 839 8899

Fax

[email protected]

Contact person for public queries

Name

Amy Gaskell

Address

Dept of Anaesthesia
Waikato Hospital
Corner Pembroke Selwyn St
Hamiton 3240

Country

New Zealand

Phone

+64 7 839 8899

Fax

[email protected]

Contact person for scientific queries

Name

Amy Gaskell

Address

Dept of Anaesthesia
Waikato Hospital
Corner Pembroke Selwyn St
Hamiton 3240

Country

New Zealand

Phone

+64 7 839 8899

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

Deidentified individual participant data may be made available on request to authors

What supporting documents are/will be available?

Doc. No.	Type	Citation	Email
19097	Study protocol	Gaskell, Amy, et al. "Modulation of frontal EEG alpha oscillations during maintenance and emergence phases of general anaesthesia to improve early neurocognitive recovery in older patients: protocol for a randomised controlled trial." Trials 20.1 (2019): 146.	[email protected]
19098	Informed consent form		[email protected]
19099	Ethical approval		[email protected]

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Modulation of frontal EEG alpha oscillations during maintenance and emergence phases of general anaesthesia to improve early neurocognitive recovery in older patients: Protocol for a randomised controlled trial.	2019	https://dx.doi.org/10.1186/s13063-019-3178-x

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically