Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618001114235
Ethics application status
Approved
Date submitted
28/06/2018
Date registered
5/07/2018
Date last updated
10/09/2023
Date data sharing statement initially provided
10/09/2023
Date results information initially provided
10/09/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
Development of Risk Models for Cognitive Decline and Delirium in Patients Undergoing Transcatheter Aortic Valve Implantation (TAVI)
Scientific title
Development of Risk Models for Cognitive Decline and Delirium in Aortic Stenosis and Transcatheter Aortic Valve Implantation (TAVI)
Secondary ID [1] 294824 0
nil known
Universal Trial Number (UTN)
U1111-1213-6749
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Aortic stenosis 307770 0
Delirium 307771 0
Cognitive decline 307772 0
Condition category
Condition code
Cardiovascular 306815 306815 0 0
Diseases of the vasculature and circulation including the lymphatic system
Mental Health 307596 307596 0 0
Other mental health disorders
Surgery 307597 307597 0 0
Other surgery

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This study will identify possible risk factors for delirium (for two days post-procedurally) and cognitive decline (at 3-, 6- and 12-months post-procedurally) in older adults undergoing transcatheter aortic valve implantation. Possible risk factors include medical history, procedural variables and a range of baseline assessments (non-invasive brain imaging (EEG), APOE-e4 genotype from a saliva sample, and symptoms of frontostriatal dysfunction (gait characteristics, visual symptoms, voice assessment, and a range of questionnaires regarding swallowing, depression, anxiety, sleep disturbance and changes to behaviour).
Participants will be required to complete a baseline assessment of 90 minutes duration, with the additional option of participating in the collection of resting EEG. The baseline assessment consists of questions about education, social and physical activity history, the Edmonton Frail Scale, The Addenbrooke's Cognitive Examination, CANTAB (The motor screening test, reaction time test and pattern recognition test), the Geriatric Depression Scale, insomnia items from the Hamilton Rating Scale for Depression, 6m gait task, dual 6m cognition/gait task, visual acuity, diplopia assessment, measuring of blink rate, one question from the Sydney Swallowing Questionnaire, three 5 second phonations of the vowel "ah" analysed using the iPad voice analyst app, the Neuropsychiatric Questionnaire, Euroqol-5D, and the Barthel Index (Modified).
For two days following the TAVI procedure, participants will be assessed for delirium and delirium severity for a duration of 20 minutes using the Confusion Assessment Method and Memorial Delirium Assessment Scale. Follow-up of 60 minutes in duration will be completed at 3-, 6- and 12- months consisting of the Addenbrooke's Cognitive Examination, CANTAB (The motor screening test, reaction time test and pattern recognition test)Euroqol-5D, and the Barthel Index (Modified).
Intervention code [1] 301142 0
Not applicable
Comparator / control treatment
The control group will be age-matched participants screened and not found to have heart murmur (i.e. non severe aortic stenosis participants). The rate of cognitive decline of the TAVI participants will be calculated based on the changes of the control group over the same time-frame.
The baseline assessment consists of questions about education, social and physical activity history, the Edmonton Frail Scale, The Addenbrooke's Cognitive Examination, CANTAB (The motor screening test, reaction time test and pattern recognition test), the Geriatric Depression Scale, insomnia items from the Hamilton Rating Scale for Depression, 6m gait task, dual 6m cognition/gait task, visual acuity, diplopia assessment, measuring of blink rate, one question from the Sydney Swallowing Questionnaire, three 5 second phonations of the vowel "ah" analysed using the iPad voice analyst app, the Neuropsychiatric Questionnaire, Euroqol-5D, and the Barthel Index (Modified).
Follow-up of 60 minutes in duration will be completed at 3-, 6- and 12- months consisting of the Addenbrooke's Cognitive Examination, CANTAB (The motor screening test, reaction time test and pattern recognition test)Euroqol-5D, and the Barthel Index (Modified).
Control group
Active

Outcomes
Primary outcome [1] 305805 0
Delirium assessed using the Confusion Assessment Method and the Confusion Assessment Method-ICU
Timepoint [1] 305805 0
one and two days post TAVI
Primary outcome [2] 305806 0
Cognitive decline measured using the Addenbrooke's Cognitive Examination and the Cambridge Neuropsychological Test Automated Battery
Timepoint [2] 305806 0
3-, 6- and 12- months post TAVI
Secondary outcome [1] 346624 0
Hospital acquired complications documented in the medical records as per the Australian Commission on Safety and Quality in Healthcare.
https://www.safetyandquality.gov.au/our-work/indicators/hospital-acquired-complications/
Timepoint [1] 346624 0
30 days
Secondary outcome [2] 346625 0
Quality of life measured using the EuroQol
Timepoint [2] 346625 0
3-, 6- and 12- months post TAVI.
Secondary outcome [3] 346626 0
Delirium severity using the Memorial Delirium Assessment Scale
Timepoint [3] 346626 0
one and two days post TAVI
Secondary outcome [4] 346627 0
Delirium subtype using Meagher's descriptions (2009).
Timepoint [4] 346627 0
one and two days post TAVI
Secondary outcome [5] 348475 0
mortality
Timepoint [5] 348475 0
3-, 6- and 12- months post TAVI.
Secondary outcome [6] 348476 0
functional activity measured using the Barthel (modified) Index
Timepoint [6] 348476 0
3-, 6- and 12- months post TAVI

Eligibility
Key inclusion criteria
Inclusion criteria for the TAVI group include undergoing elective TAVI at the Royal Adelaide Hospital, male or female, and aged over 60 years. Participants with a clinical diagnosis of a neurodegenerative condition (including dementia) will be eligible for inclusion as it is reflective of the general older population who would be considered appropriate for cardiovascular procedures and thus will facilitate clinical translation of study results (note: different consent process for those with a clinical diagnosis of dementia).
Inclusion criteria for the control group include male or female, and aged over 60 years. Participants with a clinical diagnosis of a neurodegenerative condition including dementia will be eligible for inclusion (note: different consent process for those with a clinical diagnosis of dementia).
Minimum age
60 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Key exclusion criteria include current or recent (within the past year) alcohol or substance abuse or dependence, use of recreational drugs (within the past month), a diagnosed learning disability, insufficient English language, hearing (with aids) or vision (with glasses) to complete assessment tasks.
Control participants will be excluded if they are found to have a heart murmur and/or aortic stenosis, a history of cardiovascular disease.
TAVI participants will be excluded if they are already enrolled in a TAVI clinical trial.

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Convenience sample
Timing
Prospective
Statistical methods / analysis
A base model for delirium after TAVI (using apical implantation approach, female gender, age, atrial fibrillation, creatinine, carotid disease and stroke/transient ischemic attack) had a receiver operatic characteristic (ROC) curve c-statistic of 0.79. Further research is still required as the results may have reduced generalizability given other studies have found these risk factors not to be associated with delirium. Thus, utilising G* power statistical analysis software, a priori sample size was calculated using an equivalent effect side of f2 =0.325. With f2 =0.325, power=0.95 and a=0.05, the computed sufficient sample size is n= 36 (per group). A recruitment strategy of 100 participants per group will ensure the study is sufficiently powered not only for the detection of presence vs absence of delirium, but also the assessment of delirium severity (requiring greater numbers); especially given the ambiguity for these risk factors found in other studies and risk of drop-out and death across the study period.

Data will be entered into Excel and SPSS for analysis. EEG data will be processed using software such as MATLAB, MATLAB toolboxes, ERPlab and EEGlab. Recruitment of 100 participants for each group is sufficient to ensure the study is adequately powered. The statistical methods that will be used to identify risk factors and develop risk models will include logistic regression, ridge regression and lasso. Cross-validation will be used to determine which statistical model minimises over-fitting or under-fitting. Standard multivariate regression assumptions will be examined including multivariate outliers, multicollinearity, normality of residuals and influential cases. In determining the differences between TAVI participants and control participants for cognition, mood, behaviour, sleep and motor characteristics, the appropriate parametric (e.g. t-test) or non-parametric test (e.g. Mann Whitney, Fisher-Exact test) will be selected. Multiple comparisons will be controlled for using the Holm Method. Only group-level de-identified data will be presented.

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Date of first participant enrolment
Anticipated
Actual
1/05/2018
Date of last participant enrolment
Anticipated
1/11/2019
Actual
31/05/2021
Date of last data collection
Anticipated
1/11/2020
Actual
31/05/2022
Sample size
Target
200
Accrual to date
Final
32
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 11210 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 23084 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 299421 0
Government body
Name [1] 299421 0
Research Training Program Scholarship, Department of Education and Training, Australian Government.
Country [1] 299421 0
Australia
Primary sponsor type
University
Name
University of South Australia
Address
Prof Hannah Keage
Cognitive Ageing and Impairment Neurosciences
School of Psychology, Social Work and Social Policy
Adelaide
South Australia 5000

GPO Box 2471
Adelaide
South Australia 5001
Australia
Country
Australia
Secondary sponsor category [1] 299230 0
None
Name [1] 299230 0
Address [1] 299230 0
Country [1] 299230 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300321 0
Central Adelaide Local Health Network Human Research Ethics Committee (CALHN HREC)
Ethics committee address [1] 300321 0
CALHN Research Office
L3 Roma Mitchell House, North Terrace, Adelaide, SA 5000.
Ethics committee country [1] 300321 0
Australia
Date submitted for ethics approval [1] 300321 0
21/09/2017
Approval date [1] 300321 0
13/12/2017
Ethics approval number [1] 300321 0
R20170916

Summary
Brief summary
This study aims to identify risk factors for a deterioration in thinking and memory skills after a type of heart procedure known as transcatheter aortic valve implantation (TAVI). These changes may be short-term (such as delirium) or long-term cognitive decline. There will be 100 participants undergoing TAVI and 100 age-matched controls.
Another part of this study will compare the 100 participants undergoing TAVI and the 100 control participants before the TAVI procedure i.e. the baseline data. This analysis will identify if participants with aortic stenosis compared with participants without aortic stenosis have different motor symptoms (walking, eye movement, voice, swallowing), mood, behaviour, brain activity (measured non-invasively using electroencephalogram or EEG), and their genotype taken from a saliva sample (with consent from participants).
Trial website
Trial related presentations / publications
Public notes
Protocol paper - DOI: 10.3389/fcvm.2021.657057/
Outcomes paper - DOI:10.56392/001c.74542
Attachments [1] 2828 2828 0 0
/AnzctrAttachments/375058-Delirium TAVR study Ethics Approval.pdf (Ethics approval)
Attachments [2] 2829 2829 0 0
/AnzctrAttachments/375058-Ethics ammendment approval.docx (Ethics approval)
Attachments [3] 2830 2830 0 0
/AnzctrAttachments/375058-1-TAVI consent form for self.doc (Participant information/consent)
Attachments [4] 2831 2831 0 0
/AnzctrAttachments/375058-2-TAVI consent form for person responsible ET.doc
Attachments [5] 2832 2832 0 0
/AnzctrAttachments/375058-3- Control consent form for self ET.doc (Participant information/consent)
Attachments [6] 2833 2833 0 0
/AnzctrAttachments/375058-4- Control consent form for person responsible ET.doc (Participant information/consent)
Attachments [7] 2834 2834 0 0
/AnzctrAttachments/375058-5-Family member control consent form for self ET.doc (Participant information/consent)
Attachments [8] 2836 2836 0 0
/AnzctrAttachments/375058-6-Family member TAVI consent form for self ET.doc (Participant information/consent)
Attachments [9] 2837 2837 0 0
/AnzctrAttachments/375058-TAVI Study - Erica Tilley - Assessment Booklet 15 May.docx (Other)

Contacts
Principal investigator
Name 83290 0
Prof Hannah Keage
Address 83290 0
Cognitive Ageing and Impairment Neurosciences
School of Psychology, Social Work and Social Policy
University of South Australia
Adelaide
South Australia 5000
GPO Box 2471
Adelaide
South Australia 5001
Australia
Country 83290 0
Australia
Phone 83290 0
+61 8 83024340
Fax 83290 0
Email 83290 0
[email protected]
Contact person for public queries
Name 83291 0
Hannah Keage
Address 83291 0
Cognitive Ageing and Impairment Neurosciences
School of Psychology, Social Work and Social Policy
University of South Australia
Adelaide
South Australia 5000
GPO Box 2471
Adelaide
South Australia 5001
Australia
Country 83291 0
Australia
Phone 83291 0
+61 8 83024340
Fax 83291 0
Email 83291 0
[email protected]
Contact person for scientific queries
Name 83292 0
Hannah Keage
Address 83292 0
Cognitive Ageing and Impairment Neurosciences
School of Psychology, Social Work and Social Policy
University of South Australia
Adelaide
South Australia 5000
GPO Box 2471
Adelaide
South Australia 5001
Australia
Country 83292 0
Australia
Phone 83292 0
+61 8 83024340
Fax 83292 0
Email 83292 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Data underlying primary outcomes only.
Please see https://data.unisa.edu.au/dap/Project.aspx?ProjectID=742756
When will data be available (start and end dates)?
Data is currently available with no end date determined.
Please see https://data.unisa.edu.au/dap/Project.aspx?ProjectID=742756
Available to whom?
Any member of the public has access via the below link.
Please see https://data.unisa.edu.au/dap/Project.aspx?ProjectID=742756
Available for what types of analyses?
Any purpose.
Please see https://data.unisa.edu.au/dap/Project.aspx?ProjectID=742756
How or where can data be obtained?
https://data.unisa.edu.au/dap/Project.aspx?ProjectID=742756


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
20297Data dictionary https://data.unisa.edu.au/dap/Project.aspx?ProjectID=742756[email protected]



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Ghezzi ES, Psaltis PJ, Loetscher T, et al. Factors... [More Details]

Documents added automatically
No additional documents have been identified.