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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04204915




Registration number
NCT04204915
Ethics application status
Date submitted
17/12/2019
Date registered
19/12/2019
Date last updated
16/10/2024

Titles & IDs
Public title
The Early Valve Replacement in Severe ASYmptomatic Aortic Stenosis Study
Scientific title
A Randomised Controlled Trial of Early Valve Replacement in Severe ASYmptomatic Aortic Stenosis
Secondary ID [1] 0 0
CS/18/7/33714
Secondary ID [2] 0 0
0700
Universal Trial Number (UTN)
Trial acronym
EASY-AS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Aortic Stenosis 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Aortic valve replacement

Active comparator: Group A: Aortic valve replacement - Participants randomised to AVR will be investigated and managed according to local protocols and standard practice. Participants will be placed on the waiting list with the aim that surgery will be performed within 3 months, dependent on local hospitals' waiting lists.

No intervention: Group B: Expectant management - Participants randomised to expectant management will continue to have regular monitoring of their condition in line with the procedures and standard practices of their hospital.


Treatment: Surgery: Aortic valve replacement
Participants will be assessed by a member of the surgical team performing aortic valve replacement (AVR), and by any other relevant medical professionals identified by the doctors overseeing their care in hospital. When deemed ready for AVR, a member of the surgical team will ask for consent to proceed with the AVR. They will discuss the surgical procedure, covering information on the basic technical procedure, risks and expected recovery time.
Intervention code [1] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Combined measure of cardiovascular death and hospitalisation for heart failure
Timepoint [1] 0 0
Minimum 3 years
Secondary outcome [1] 0 0
WHO Disability Assessment Schedule (WHODAS 2.0)
Timepoint [1] 0 0
6, 12, 24 and 36 months
Secondary outcome [2] 0 0
NHS record linkage services
Timepoint [2] 0 0
Up to 5 years
Secondary outcome [3] 0 0
Death (cardiovascular, including sudden cardiac death, and non-cardiovascular), hospitalisation for heart failure, myocardial infarction, stroke
Timepoint [3] 0 0
Up to 5 years
Secondary outcome [4] 0 0
Number of additional outcomes of special interest: infective endocarditis and major bleeding, resuscitated cardiac arrest, hospitalisation with new onset atrial fibrillation, syncope, revascularization (CABG/PCI), cardiac device implantation
Timepoint [4] 0 0
Up to 5 years
Secondary outcome [5] 0 0
EuroQol five-level (EQ-5D-5L) questionnaire
Timepoint [5] 0 0
6, 12, 24 and 36 months
Secondary outcome [6] 0 0
Health Economics Questionnaire
Timepoint [6] 0 0
6, 12, 24 and 36 months
Secondary outcome [7] 0 0
Edmonton Frail Scale (EFS) (Bedside and Acute Care Version)
Timepoint [7] 0 0
Baseline

Eligibility
Key inclusion criteria
1. Age >18 years
2. Patient has severe asymptomatic AS, in line with current international guidelines, defined as either:

1. Peak velocity =4m/s OR mean pressure gradient =40mmHg WITH aortic valve area =1.0cm2 OR =0.6cm2/m2 body surface area OR
2. Peak velocity =4m/s OR mean pressure gradient =40mmHg WITH aortic valve area >1.0 - =1.2cm2 OR >0.6 - =0.7cm2/m2 body surface area AND high sex specific calcium score* OR
3. Peak Velocity =3.5m/s - 3.9m/s AND mean pressure gradient <40 mmHg WITH aortic valve area =1.0cm2 OR =0.6cm2/m2 body surface area AND high sex specific calcium score* *Sex specific high calcium scores (Agatston units): >1200 females; >2000 males
3. The responsible clinician feels that either ongoing surveillance or early AVR are appropriate.
4. Regarded by the treating cardiologist to be suitable for AVR (surgical or TAVI) with an acceptable risk
5. Willing to provide informed consent and be randomised to early AVR or expectant management
6. An ability to understand one of the written languages that the study has provided written and visual materials in, or the availability of a translator to explain the study documentation
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
7. Symptoms related to AS
8. Additional severe valvular heart disease
9. Other cardiac surgery planned pre-randomisation (eg CABG)
10. Left ventricular systolic dysfunction (LVEF <50%)
11. Pregnancy
12. Co-morbid condition that, in the opinion of the treating cardiologist, limits life expectancy to <2 years
13. Patient has previously undergone AVR or TAVI with restenosis

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/03/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/04/2031
Actual
Sample size
Target
2844
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
CanberraNSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Canberra Hospital - Garran
Recruitment hospital [2] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [3] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [4] 0 0
Westmead Hospital - Westmead
Recruitment hospital [5] 0 0
Wollongong Hospital - Wollongong
Recruitment hospital [6] 0 0
Prince Charles Hospital - Chermside
Recruitment hospital [7] 0 0
Townsville Hospital - Douglas
Recruitment hospital [8] 0 0
The Gold Coast Hospital - Southport
Recruitment hospital [9] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [10] 0 0
Flinders Medical Centre - Adelaide
Recruitment hospital [11] 0 0
Monash Health - Clayton
Recruitment hospital [12] 0 0
University Hospital Geelong - Geelong
Recruitment hospital [13] 0 0
Fiona Stanley Hospital - Perth
Recruitment hospital [14] 0 0
Royal Perth Hospital - Perth
Recruitment hospital [15] 0 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [16] 0 0
Northern Hospital - Epping
Recruitment hospital [17] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [18] 0 0
Nepean Hospital - Kingswood
Recruitment hospital [19] 0 0
John Hunter Hospital - New Lambton Heights
Recruitment hospital [20] 0 0
Royal Darwin Hospital - Tiwi
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
2170 - Liverpool
Recruitment postcode(s) [3] 0 0
2065 - St Leonards
Recruitment postcode(s) [4] 0 0
2145 - Westmead
Recruitment postcode(s) [5] 0 0
2500 - Wollongong
Recruitment postcode(s) [6] 0 0
4032 - Chermside
Recruitment postcode(s) [7] 0 0
4814 - Douglas
Recruitment postcode(s) [8] 0 0
4215 - Southport
Recruitment postcode(s) [9] 0 0
5000 - Adelaide
Recruitment postcode(s) [10] 0 0
SA 5042 - Adelaide
Recruitment postcode(s) [11] 0 0
3168 - Clayton
Recruitment postcode(s) [12] 0 0
3220 - Geelong
Recruitment postcode(s) [13] 0 0
6150 - Perth
Recruitment postcode(s) [14] 0 0
WA6000 - Perth
Recruitment postcode(s) [15] 0 0
SA 5112 - Elizabeth Vale
Recruitment postcode(s) [16] 0 0
VIC 3076 - Epping
Recruitment postcode(s) [17] 0 0
TAS 7000 - Hobart
Recruitment postcode(s) [18] 0 0
NSW 2747 - Kingswood
Recruitment postcode(s) [19] 0 0
NSW 2305 - New Lambton Heights
Recruitment postcode(s) [20] 0 0
TIWI NT 0810 - Tiwi
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Brugge
Country [2] 0 0
Belgium
State/province [2] 0 0
Genk
Country [3] 0 0
Belgium
State/province [3] 0 0
Jette
Country [4] 0 0
New Zealand
State/province [4] 0 0
Auckland
Country [5] 0 0
New Zealand
State/province [5] 0 0
Christchurch
Country [6] 0 0
New Zealand
State/province [6] 0 0
Dunedin
Country [7] 0 0
Serbia
State/province [7] 0 0
Sremska Kamenica
Country [8] 0 0
United Kingdom
State/province [8] 0 0
County Durham
Country [9] 0 0
United Kingdom
State/province [9] 0 0
Denbighshire
Country [10] 0 0
United Kingdom
State/province [10] 0 0
Dorset
Country [11] 0 0
United Kingdom
State/province [11] 0 0
Hampshire
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Leicestershire
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Merseyside
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Norfolk
Country [15] 0 0
United Kingdom
State/province [15] 0 0
North Lincolnshire
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Northamptonshire
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Northumberland
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Scotland
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Somerset
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Wales
Country [21] 0 0
United Kingdom
State/province [21] 0 0
West Midlands
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Wycombe
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Aberdeen
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Aintree
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Ayr
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Basildon
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Birmingham
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Blackpool
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Brighton
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Carlisle
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Chesterfield
Country [32] 0 0
United Kingdom
State/province [32] 0 0
Coventry
Country [33] 0 0
United Kingdom
State/province [33] 0 0
Darlington
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Doncaster
Country [35] 0 0
United Kingdom
State/province [35] 0 0
Edinburgh
Country [36] 0 0
United Kingdom
State/province [36] 0 0
Exeter
Country [37] 0 0
United Kingdom
State/province [37] 0 0
Gateshead
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Glasgow
Country [39] 0 0
United Kingdom
State/province [39] 0 0
Huddersfield
Country [40] 0 0
United Kingdom
State/province [40] 0 0
Isleworth
Country [41] 0 0
United Kingdom
State/province [41] 0 0
Keighley
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Kilmarnock
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Leeds
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Lincoln
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Liverpool
Country [46] 0 0
United Kingdom
State/province [46] 0 0
London
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Maidstone
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Manchester
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Middlesbrough
Country [50] 0 0
United Kingdom
State/province [50] 0 0
Newcastle upon Tyne
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Nottingham
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Paisley
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Plymouth
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Poole
Country [55] 0 0
United Kingdom
State/province [55] 0 0
Portsmouth
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Sheffield
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Southampton
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Stirling
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Stockport
Country [60] 0 0
United Kingdom
State/province [60] 0 0
Stockton-on-Tees
Country [61] 0 0
United Kingdom
State/province [61] 0 0
Torquay
Country [62] 0 0
United Kingdom
State/province [62] 0 0
Truro
Country [63] 0 0
United Kingdom
State/province [63] 0 0
Wakefield
Country [64] 0 0
United Kingdom
State/province [64] 0 0
Warwick
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Watford
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Yeovil

Funding & Sponsors
Primary sponsor type
Other
Name
University of Leicester
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
University of Auckland, New Zealand
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
University Hospitals, Leicester
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
The University of Western Australia
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Aortic stenosis (AS) affects approximately 5% of individuals \>65 years old, with \~3% of people \>75 years having moderate to severe disease. The prevalence of AS is rising rapidly due to an ageing population and is projected to double in the next two decades. Increasingly clinicians face the dilemma of how to best manage this growing population of mainly elderly patients, many of whom are asymptomatic but have been identified as having severe AS, often as an incidental finding. Reduced aortic valve opening progresses over decades without any apparent symptoms because the heart compensates for the AS. Ultimately, compensatory mechanisms fail resulting in angina, syncope or heart failure. If these symptomatic patients with severe AS remain untreated, they have a dire prognosis. In this situation the only effective treatment is AVR, either surgically or using TAVI. Conversely, conventional teaching and clinical practice in cardiology has been that, in the absence of symptoms, the prognosis is usually excellent and, except in a few very specific circumstances, conservative management and regular review (expectant management) is recommended. This advice is reflected in current international guidelines but is based largely on historical precedent. There has never been a randomised controlled trial to address the relative benefits of early AVR versus expectant management in patients with severe asymptomatic AS. The relative benefits of a strategy of early AVR/TAVI versus expectant management in patients with asymptomatic severe AS are unclear. There is clinical equipoise but it remains one of the few areas of cardiovascular medicine where no randomised controlled trials (RCT) have been performed. The EASY-AS study will provide crucial data on the relative merits of these differing approaches to management, in terms of important patient orientated outcomes, conventional cardiovascular end-points and cost effectiveness.
Trial website
https://clinicaltrials.gov/study/NCT04204915
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gerry McCann, Prof
Address 0 0
University of Leicester
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Carla Richardson
Address 0 0
Country 0 0
Phone 0 0
+44 0116-229-7936
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04204915