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Trial registered on ANZCTR


Registration number
ACTRN12618000433202
Ethics application status
Approved
Date submitted
7/03/2018
Date registered
26/03/2018
Date last updated
18/10/2019
Date data sharing statement initially provided
12/03/2019
Date results information initially provided
18/10/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Exploring Australian Comparative Effectiveness of Transcatheter heart valve technology for aortic stenosis.
Scientific title
Exploring Australian Comparative Effectiveness of Transcatheter heart valve technology for aortic stenosis.
Secondary ID [1] 294211 0
None
Universal Trial Number (UTN)
U1111-1210-1662
Trial acronym
ACET
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Aortic stenosis 306861 0
Condition category
Condition code
Cardiovascular 305958 305958 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The primary comparison of this observational study is between patients receiving transcatheter aortic valve replacement (TAVR) and those not receiving any form of aortic value replacement. The secondary comparison of this observational study is between patients receiving transcatheter aortic valve replacement and surgical aortic valve replacement. Retrospective data will be used along with a small subset of eligible patients who will be prospectively recruited when placed on waiting lists for these procedures. This will enable completion of quality of life assessments (EQ-5D) at baseline and 12 months for quality of life modelling for health economic analysis.

As such, prospective eligible patients will be reviewed when placed on the waiting list for procedures and will be recruited if eligible prior to any potential TAVI/SAVR procedures. This will enable completion of quality of life assessments (EQ-5D) at baseline and 12 months for quality of life modelling for health economic analysis.

For prospective patients, the data will be collected until 12 months post-enrolment (as per the date of last data collection). For retrospective patients, data may be collected for up to 5 years prior to the date of last data collection.
Intervention code [1] 300501 0
Not applicable
Comparator / control treatment
A small subset of prospective eligible medically managed patients will be recruited within 1 month of diagnosis/admission which will constitute the population of patients not receiving any form of aortic valve replacement. This will enable completion of quality of life assessments (EQ-5D) at baseline and 12 months for quality of life modelling for health economic analysis.
Control group
Active

Outcomes
Primary outcome [1] 304998 0
Time to death, defined as all-cause mortality

Data will be obtained through data linkage of public and private hospital admissions and care through medical records system. Births, deaths and marriages and the national death index will be used to collect mortality and cause of death data.

Timepoint [1] 304998 0
12 months and up to 5 years post enrolment
Primary outcome [2] 304999 0
Time to Heart Failure re-hospitalisation, defined as admission to hospital with ICD-10AM code of I50.X in any of the top 5 diagnosis positions.

Data will be obtained through data linkage of public and private hospital admissions and care through medical records system. Data will be obtained through data linkage of public and private hospital admissions and care through medical records system. Births, deaths and marriages and the national death index will be used to collect mortality and cause of death data.
Timepoint [2] 304999 0
12 months and up to 5 years post enrolment
Secondary outcome [1] 343836 0
Time to myocardial infarction: chest pain/discomfort associated with a rise and fall in cardiac biomarkers, or a new myocardial wall motion defect on echocardiography and consistent with the new Universal Definition.

Data will be obtained through data linkage of public and private hospital admissions and care through medical records system.
Timepoint [1] 343836 0
12 months and up to 5 years post enrolment
Secondary outcome [2] 343837 0
Time to stroke: New onset neurological defect consistent with a single contiguous vascular territory, with supportive cerebral imaging.

Data will be obtained through data linkage of public and private hospital admissions and care through medical records system.
Timepoint [2] 343837 0
12 months and up to 5 years post enrolment
Secondary outcome [3] 343838 0
Time to cardiovascular hospitalisation (composite outcome): coronary revascularisation (PCI or CABG); cerebrovascular accidents with supportive cerebral imaging; atrial or ventricular cardiac arrhythmias; CCF without myocardial infarction; peripheral vascular revascularisation; unstable angina, reoperation for surgical bleeding; surgical wound infection; pericardial effusion; and valvular dysfunction as documented by a hospital discharge summary or diagnosis-related group report.

Data will be obtained through data linkage of public and private hospital admissions and care through medical records system.
Timepoint [3] 343838 0
12 months and up to 5 years post enrolment
Secondary outcome [4] 343839 0
Time to any re-hospitalization: Any admission to hospital as documented by a hospital discharge summary or diagnosis-related group report.

Data will be obtained through data linkage of public and private hospital admissions and care through medical records system.
Timepoint [4] 343839 0
12 months and up to 5 years post enrolment
Secondary outcome [5] 343840 0
Days free from hospital admission: From a patient-focused perspective, this outcome will measure the total number of days spent admitted/not admitted to an acute care/rehabilitation facility as a proportion of their follow-up duration.

Data will be obtained through data linkage of public and private hospital admissions and care through medical records system.
Timepoint [5] 343840 0
12 months and up to 5 years post enrolment
Secondary outcome [6] 344339 0
Health-related quality of life (EQ5D)

This will be collected via follow up phone call or mail-out.
Timepoint [6] 344339 0
Baseline and 12 months

Eligibility
Key inclusion criteria
1. Patients aged 65 years and above with clinical symptoms consistent with aortic stenosis, being syncope, exertional angina and congestive cardiac failure.

2. Echocardiographic evidence of severe aortic stenosis defined as an estimated aortic valve area of <1.0cm2
Minimum age
65 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Advanced malignancy defined as untreatable disease with a life-expectancy of <12 months, as determined by the treating oncology specialist.
2. Prior aortic valve surgery.
3. Aortic stenosis resulting from a congenital bicuspid aortic valve.
4. Patients already classified as requiring high-level care in a nursing home.
5. Cardiac Surgery requiring double (aortic and mitral) valve replacement.

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Both
Statistical methods / analysis
Fatal and non-fatal clinical events remain very high and protracted longitudinal follow-up will result in a more thorough assessment of late clinical events. Nevertheless, a conservative approach of using mortality alone has been used. Furthermore, “confounding by indication” is recognized as a powerful influence on the required sample size, accounting for up to 50% of the treatment effect observed within registries as compared with randomized studies. Therefore, a conservative estimate of effect has been used to calculate power and sample size.
Literature-based estimates of mortality among conservatively managed aortic stenosis patients by 5 years is ~60%. The 1-year mortality rate of 5% for surgical AVR patients has been estimated from the Flinders Medical Centre cardiac surgical database. Given the retrospective nature of this analysis, we will seek to include ~160 TAVR/AVR patients, potentially through the involvement of several centres. Assuming an adjusted non-inferiority margin of 5%, this sample size has 87% power to ensure that the TAVR survival rate is not clinically inferior to surgical AVR before the cost effectiveness analysis is undertaken. Assuming up to a 5% difference in overall clinical outcomes, and a standard deviation in costs of $25,000, this sample size then has >80% power to detect a cost difference of $9000 between the TAVR and surgical AVR group assuming a willingness to pay of $50,000 per life year saved. Given the observational nature of the cohort comparisons, no adjustment for multiple comparisons has been undertaken in this component of the study.

Recruitment
Recruitment status
Active, not 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 in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 13368 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 25968 0
5042 - Bedford Park

Funding & Sponsors
Funding source category [1] 298848 0
Commercial sector/Industry
Name [1] 298848 0
Edwards Lifesciences
Address [1] 298848 0
Edwards Lifesciences Corp.
One Edwards Way, Irvine,
California 92614
Country [1] 298848 0
United States of America
Primary sponsor type
Individual
Name
Prof Derek Chew
Address
Flinders Medical Centre,
1 Flinders Dr, Bedford Park
South Australia 5042
Country
Australia
Secondary sponsor category [1] 298046 0
University
Name [1] 298046 0
Flinders University
Address [1] 298046 0
1 Flinders Dr, Bedford Park SA 5042
Country [1] 298046 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299792 0
Southern Adelaide Clinical Human Research Ethics Committee (SACHREC)
Ethics committee address [1] 299792 0
Ethics committee country [1] 299792 0
Australia
Date submitted for ethics approval [1] 299792 0
06/04/2018
Approval date [1] 299792 0
31/08/2018
Ethics approval number [1] 299792 0

Summary
Brief summary
Traditionally, the only treatment options for patients diagnosed with severe aortic stenosis were relatively invasive interventions such as surgical aortic heart value replacement (SAVR) or balloon aortic valvuloplasty (BAV), or non-invasive treatment such as medical therapy. The preferred treatment option for patients with severe aortic stenosis has long-been surgical aortic value replacement (SAVR) due to the superior outcomes over medical therapy, however, a number of patients, such as those in advanced age with additional diseases, have not been suitable for surgery, often due to the considerable risks associated with surgical procedures in these patients.

More recently, there has been the development of a procedure known as transcatheter aortic heart value implantation (TAVI) which is a less invasive surgical procedure than the standard surgical aortic valve replacement (SAVR) and has allowed doctors to treat patients with severe aortic stenosis who have previously not been suitable for the surgical intervention. This TAVI procedure could therefore be beneficial to many patients with severe aortic stenosis who have been considered too high-risk to undergo the standard surgical procedure and have had to rely on medical therapy alone.

What we therefore aim to do in this study is to find out the value of the TAVI procedure in comparison to other treatment options, both surgical and non-surgical, by looking at patient outcomes, patient quality of life and cost effectiveness of those undergoing each of the treatment options.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 81582 0
Prof Derek Chew
Address 81582 0
Flinders Medical Centre
1 Flinders Dr, Bedford Park
South Australia 5042
Country 81582 0
Australia
Phone 81582 0
+61884042001
Fax 81582 0
Email 81582 0
derek.chew@flinders.edu.au
Contact person for public queries
Name 81583 0
Dr Erin Morton
Address 81583 0
Department of Cardiovascular Medicine, Flinders Medical Centre

1 Flinders Drive, Bedford Park 5042
South Australia
Country 81583 0
Australia
Phone 81583 0
+610882045836
Fax 81583 0
Email 81583 0
erin.morton@flinders.edu.au
Contact person for scientific queries
Name 81584 0
Prof Derek Chew
Address 81584 0
Flinders Medical Centre
1 Flinders Dr, Bedford Park
South Australia 5042
Country 81584 0
Australia
Phone 81584 0
+61884042001
Fax 81584 0
Email 81584 0
derek.chew@flinders.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
This was not part of the original protocol but will be considered upon completion of the trial dependent on appropriate approvals.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary