The Early Valve Replacement in Severe ASYmptomatic Aortic Stenosis Study
EASY-AS
A Randomised Controlled Trial of Early Valve Replacement in Severe ASYmptomatic Aortic Stenosis
4 other identifiers
interventional
2,844
7 countries
110
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 Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Mar 2020
Longer than P75 for not_applicable
110 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 17, 2019
CompletedFirst Posted
Study publicly available on registry
December 19, 2019
CompletedStudy Start
First participant enrolled
March 10, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2031
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 1, 2031
September 25, 2025
September 1, 2025
11.1 years
December 17, 2019
September 24, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Combined measure of cardiovascular death and hospitalisation for heart failure
Measured in days from randomisation until end of trial (minimum 3 years). The primary analysis will be undertaken when 663 events have accrued, which is estimated to be after a median of 5 years follow-up assuming 2844 patients are recruited over 4 years.
Minimum 3 years
Secondary Outcomes (7)
WHO Disability Assessment Schedule (WHODAS 2.0)
6, 12, 24 and 36 months
NHS record linkage services
Up to 5 years
Death (cardiovascular, including sudden cardiac death, and non-cardiovascular), hospitalisation for heart failure, myocardial infarction, stroke
Up to 5 years
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
Up to 5 years
EuroQol five-level (EQ-5D-5L) questionnaire
6, 12, 24 and 36 months
- +2 more secondary outcomes
Study Arms (2)
Group A: Aortic valve replacement
ACTIVE COMPARATORParticipants 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.
Group B: Expectant management
NO INTERVENTIONParticipants randomised to expectant management will continue to have regular monitoring of their condition in line with the procedures and standard practices of their hospital.
Interventions
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.
Eligibility Criteria
You may qualify if:
- Age \>18 years
- Patient has severe asymptomatic AS, in line with current international guidelines, defined as either:
- Peak velocity ≥4m/s OR mean pressure gradient ≥40mmHg WITH aortic valve area ≤1.0cm2 OR ≤0.6cm2/m2 body surface area OR
- 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
- 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
- The responsible clinician feels that either ongoing surveillance or early AVR are appropriate.
- Regarded by the treating cardiologist to be suitable for AVR (surgical or TAVI) with an acceptable risk
- Willing to provide informed consent and be randomised to early AVR or expectant management
- 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
You may not qualify if:
- Symptoms related to AS
- Additional severe valvular heart disease
- Other cardiac surgery planned pre-randomisation (eg CABG)
- Left ventricular systolic dysfunction (LVEF \<50%)
- Pregnancy
- Co-morbid condition that, in the opinion of the treating cardiologist, limits life expectancy to \<2 years
- Patient has previously undergone AVR or TAVI with restenosis
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Leicesterlead
- University of Auckland, New Zealandcollaborator
- University Hospitals, Leicestercollaborator
- The University of Western Australiacollaborator
Study Sites (110)
Canberra Hospital
Garran, Australian Capital Territory, 2605, Australia
Liverpool Hospital
Liverpool, New South Wales, 2170, Australia
Royal North Shore Hospital
St Leonards, New South Wales, 2065, Australia
Westmead Hospital
Westmead, New South Wales, 2145, Australia
Wollongong Hospital
Wollongong, New South Wales, 2500, Australia
Prince Charles Hospital
Chermside, Queensland, 4032, Australia
Townsville Hospital
Douglas, Queensland, 4814, Australia
The Gold Coast Hospital
Southport, Queensland, 4215, Australia
Royal Adelaide Hospital
Adelaide, South Australia, 5000, Australia
Flinders Medical Centre
Adelaide, South Australia, SA 5042, Australia
Monash Health
Clayton, Victoria, 3168, Australia
University Hospital Geelong
Geelong, Victoria, 3220, Australia
Fiona Stanley Hospital
Perth, Western Australia, 6150, Australia
Royal Perth Hospital
Perth, Western Australia, WA6000, Australia
Lyell McEwin Hospital
Elizabeth Vale, SA 5112, Australia
Northern Hospital
Epping, VIC 3076, Australia
Royal Hobart Hospital
Hobart, TAS 7000, Australia
Nepean Hospital
Kingswood, NSW 2747, Australia
John Hunter Hospital
New Lambton Heights, NSW 2305, Australia
Royal Darwin Hospital
Tiwi, TIWI NT 0810, Australia
Sint-Jan Hospital
Bruges, 8000, Belgium
Ziekenhuis Oost-Limburg
Genk, 3600, Belgium
University Hospital of Brussels
Jette, 1090, Belgium
Frisius Medical Center
Leeuwarden, Netherlands
Radboud University Medical Center
Nijmegen, Netherlands
Auckland City Hospital
Auckland, 1023, New Zealand
Christchurch Hospital
Christchurch, 8011, New Zealand
Dunedin Hospital
Dunedin, 9016, New Zealand
Institute of Cardiovascular Diseases
Kamenitz, 21204, Serbia
Hospital Germans Trias
Barcelona, Spain
University Hospital of Navarra
Pamplona, Spain
University Hospital of North Durham
Durham, County Durham, DH1 5TW, United Kingdom
Glan Clwyd Hospital
Bodelwyddan, Denbighshire, LL18 5UJ, United Kingdom
Dorset County Hospital
Dorchester, Dorset, DT1 2JY, United Kingdom
Basingstoke and North Hampshire Hospital
Basingstoke, Hampshire, RG24 9NA, United Kingdom
University Hospitals Leicester, Glenfield
Leicester, Leicestershire, LE3 9QP, United Kingdom
Royal Liverpool Hospital
Liverpool, Merseyside, L7 8YE, United Kingdom
Norfolk and Norwich University Hospital
Norwich, Norfolk, NR4 7UY, United Kingdom
Scunthorpe General Hospital
Scunthorpe, North Lincolnshire, DN15 7BH, United Kingdom
Kettering General Hospital
Kettering, Northamptonshire, NN16 8UZ, United Kingdom
Wansbeck General Hospital
Ashington, Northumberland, NE63 9JJ, United Kingdom
Raigmore Hospital
Inverness, Scotland, IV2 3UJ, United Kingdom
Musgrove Park Hospital
Taunton, Somerset, TA1 5DA, United Kingdom
Morriston Hospital
Swansea, Wales, SA6 6NL, United Kingdom
Russells Hall Hospital
Dudley, West Midlands, DY1 2HQ, United Kingdom
George Eliot Hospital
Nuneaton, West Midlands, CV10 7DJ, United Kingdom
Walsall Manor Hospital
Walsall, West Midlands, WS2 9PS, United Kingdom
Sandwell General Hospital
West Bromwich, West Midlands, B71 4HJ, United Kingdom
Wycombe Hospital
High Wycombe, Wycombe, HP11 2TT, United Kingdom
Aberdeen Royal Infirmary
Aberdeen, AB25 2ZN, United Kingdom
Aintree University Hospital
Aintree, L9 7AL, United Kingdom
University Hospital Ayr
Ayr, KA6 6DX, United Kingdom
Barnsley Hospital NHS Foundation Trust
Barnsley, United Kingdom
Basildon University Hospital
Basildon, SS16 5NL, United Kingdom
Queen Elizabeth Hospital
Birmingham, B15 2GW, United Kingdom
Blackpool Victoria Hospital
Blackpool, FY3 8NR, United Kingdom
Royal Sussex County Hospital
Brighton, BN2 5BE, United Kingdom
North Cumbria Integrated Care
Carlisle, CA2 7AF, United Kingdom
Chesterfield Royal Hospital
Chesterfield, S44 5BL, United Kingdom
University Hospital Coventry & Warwickshire
Coventry, CV2 2DX, United Kingdom
County Durham and Darlington NHS Foundation Trust
Darlington, DL3 6HX, United Kingdom
Doncaster Royal Infirmary
Doncaster, DN2 5LT, United Kingdom
Ninewells Hospital
Dundee, United Kingdom
The Royal Infirmary of Edinburgh
Edinburgh, EH16 4SA, United Kingdom
Royal Devon & Exeter Hospital
Exeter, EX2 5DW, United Kingdom
Gateshead Health NHS Foundation Trust
Gateshead, NE9 6SX, United Kingdom
Golden Jubilee National Hospital
Glasgow, G81 4DY, United Kingdom
Glasgow Royal Infirmary
Glasgow, United Kingdom
Queen Elizabeth University Hospital
Glasgow, United Kingdom
Gloucestershire Hospitals NHS Foundation
Gloucester, United Kingdom
Huddersfield Royal Infirmary
Huddersfield, HD3 3EA, United Kingdom
West Middlesex University Hospital
Isleworth, TW7 6AF, United Kingdom
Airedale General Hospital
Keighley, BD20 6TD, United Kingdom
University Hospital Crosshouse
Kilmarnock, KA2 0BE, United Kingdom
Leeds General Infirmary
Leeds, LS1 3EX, United Kingdom
Lincoln County Hospital
Lincoln, LN2 5QY, United Kingdom
Liverpool Heart and Chest Hospital
Liverpool, L14 3PE, United Kingdom
Royal Liverpool Hospital
Liverpool, L7 8XP, United Kingdom
St Bartholomew's Hospital
London, EC1A 7BE, United Kingdom
St Thomas' Hospital
London, SE1 7EH, United Kingdom
University Hospital Lewisham
London, SE13 6LH, United Kingdom
Chelsea and Westminster Hospital
London, SW10 9NH, United Kingdom
St George's Hospital
London, SW17 0QT, United Kingdom
Cleveland Clinic London Hospital
London, SW1X 7HY, United Kingdom
Imperial College Healthcare NHS Trust
London, United Kingdom
Maidstone & Tunbridge Wells Hospital
Maidstone, ME16 9QQ, United Kingdom
Wythenshawe Hospital
Manchester, M23 9LT, United Kingdom
North Manchester General Hospital
Manchester, M8 5RB, United Kingdom
The James Cook University Hospital
Middlesbrough, TS4 3BW, United Kingdom
Freeman Hospital
Newcastle upon Tyne, NE7 7DN, United Kingdom
Kings Mill Hospital
Nottingham, NG17 4JL, United Kingdom
Queens Medical Centre
Nottingham, NG7 2UH, United Kingdom
Royal Alexandra Hospital
Paisley, PA2 9PN, United Kingdom
Derriford Hospital
Plymouth, PL6 8DH, United Kingdom
Poole Hospital
Poole, BH15 2JB, United Kingdom
Queen Alexandra Hospital
Portsmouth, PO6 3LY, United Kingdom
Northern General Hospital
Sheffield, S5 7AU, United Kingdom
Southampton General Hospital
Southampton, SO16 6YD, United Kingdom
Forth Valley Royal Hospital
Stirling, FK9 4SW, United Kingdom
Stepping Hill Hospital
Stockport, SK2 7JE, United Kingdom
North Tees and Hartlepool NHS Foundation Trust
Stockton-on-Tees, TS19 8PE, United Kingdom
South Tyneside and Sunderland NHS Foundation Trust
Sunderland, United Kingdom
Torbay Hospital
Torquay, TQ2 7AA, United Kingdom
Royal Cornwall Hospital
Truro, TR1 3LJ, United Kingdom
Pinderfields Hospital
Wakefield, WF1 4DG, United Kingdom
South Warwickshire University NHS Foundation Trust
Warwick, United Kingdom
Watford General Hospital
Watford, WD18 0HB, United Kingdom
New Cross Hospital
Wolverhampton, United Kingdom
Worcester Acute Hospitals NHS FT
Worcester, United Kingdom
Yeovil District Hospital
Yeovil, BA21 4AT, United Kingdom
Related Publications (1)
Allmark P, Taylor B, Tod AM, Ryan T, Dweck M, McCann GP, Singh A. Factors influencing the decision to accept or decline aortic valve replacement for asymptomatic aortic stenosis: a nested longitudinal qualitative substudy of the EASY-AS randomised trial. BMJ Open. 2026 Jan 22;16(1):e106485. doi: 10.1136/bmjopen-2025-106485.
PMID: 41571417DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Gerry McCann, Prof
University of Leicester
- PRINCIPAL INVESTIGATOR
Graham Hillis, Prof
The University of Western Australia
- PRINCIPAL INVESTIGATOR
Ralph Stewart, Prof
University of Aukland
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 17, 2019
First Posted
December 19, 2019
Study Start
March 10, 2020
Primary Completion (Estimated)
April 1, 2031
Study Completion (Estimated)
April 1, 2031
Last Updated
September 25, 2025
Record last verified: 2025-09
Data Sharing
- IPD Sharing
- Will not share