Aortic StenosisEASY-ASNCT04204915
The Early Valve Replacement in Severe ASYmptomatic Aortic Stenosis Study
A study testing Aortic valve replacement in people with Aortic Stenosis, run by University of Leicester at 110 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aortic Stenosis
- What is being tested?
- Aortic valve replacement
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,104 participants
- Where
- 110 sitesin 7 countries
- Study dates
- 10 Mar 2020to 1 Apr 2031
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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
Trial locations and contacts
110 sites in 7 countries. Contact the study team or a site near you to ask about taking part.
Michael Walters contact
110 sites in 7 countries
United Kingdom79 sites, 77 recruiting
- Recruiting
Aberdeen Royal Infirmary
Aberdeen, AB25 2ZN
Dr Ciprian Dospinescu
Mr Hussein El-Shafei
- Recruiting
Aintree University Hospital
Aintree, L9 7AL
Dr Prathap Kanagala
- Recruiting
Wansbeck General Hospital
Ashington, Northumberland, NE63 9JJ
Dr David Ripley
- Recruiting
University Hospital Ayr
Ayr, KA6 6DX
Dr Jim McGowan
- Recruiting
Barnsley Hospital NHS Foundation Trust
Barnsley
Deoraj Zamfar
- Recruiting
Basildon University Hospital
Basildon, SS16 5NL
Dr Jason Dungu
- Recruiting
Basingstoke and North Hampshire Hospital
Basingstoke, Hampshire, RG24 9NA
Dr Jason Glover
- Recruiting
Queen Elizabeth Hospital
Birmingham, B15 2GW
Professor Rick Steeds
- Recruiting
Blackpool Victoria Hospital
Blackpool, FY3 8NR
Professor Nidal Bittar
- Recruiting
Glan Clwyd Hospital
Bodelwyddan, Denbighshire, LL18 5UJ
Satheesh Nair
- Recruiting
Royal Sussex County Hospital
Brighton, BN2 5BE
Dr David Hildick-Smith
- Recruiting
North Cumbria Integrated Care
Carlisle, CA2 7AF
Dr Rhidian Shelton
- Recruiting
Chesterfield Royal Hospital
Chesterfield, S44 5BL
Dr Justin Cooke
- Recruiting
University Hospital Coventry & Warwickshire
Coventry, CV2 2DX
Dr Luke Tapp
Dr Jamal Khan
- Recruiting
County Durham and Darlington NHS Foundation Trust
Darlington, DL3 6HX
Dr Darragh Twomey
- Recruiting
Doncaster Royal Infirmary
Doncaster, DN2 5LT
Dr Gillian Payne
- Withdrawn
Dorset County Hospital
Dorchester, Dorset, DT1 2JY
- Recruiting
Russells Hall Hospital
Dudley, West Midlands, DY1 2HQ
Craig Barr
- Recruiting
Ninewells Hospital
Dundee
Chim Lang
- Recruiting
University Hospital of North Durham
Durham, County Durham, DH1 5TW
Darragh Twomey
- Recruiting
The Royal Infirmary of Edinburgh
Edinburgh, EH16 4SA
Professor Marc Dweck
Professor David Newby
- Recruiting
Royal Devon & Exeter Hospital
Exeter, EX2 5DW
Dr Andrew Ludman
- Recruiting
Gateshead Health NHS Foundation Trust
Gateshead, NE9 6SX
Dr Ashfaq Mohammed
- Recruiting
Golden Jubilee National Hospital
Glasgow, G81 4DY
Dr Nawwar Al-Attar
- Recruiting
Glasgow Royal Infirmary
Glasgow
Dr Stuart Watkins
- Recruiting
Queen Elizabeth University Hospital
Glasgow
Fraser Graham
- Recruiting
Gloucestershire Hospitals NHS Foundation
Gloucester
Val Nikolaidou
- Recruiting
Wycombe Hospital
High Wycombe, Wycombe, HP11 2TT
Dr Piers Clifford
- Recruiting
Huddersfield Royal Infirmary
Huddersfield, HD3 3EA
Dr Hossam El Mahy
- Recruiting
Raigmore Hospital
Inverness, Scotland, IV2 3UJ
Stephen Leslie
- Recruiting
West Middlesex University Hospital
Isleworth, TW7 6AF
Dr Gajen Sunthar Kanaganayagam
- Recruiting
Airedale General Hospital
Keighley, BD20 6TD
Dr Haqeel Jamil
- Recruiting
Kettering General Hospital
Kettering, Northamptonshire, NN16 8UZ
Dr Kai Hogrefe
- Recruiting
University Hospital Crosshouse
Kilmarnock, KA2 0BE
Dr Angie Ghattas
- Recruiting
Leeds General Infirmary
Leeds, LS1 3EX
Professor John Greenwood
- Recruiting
University Hospitals Leicester, Glenfield
Leicester, Leicestershire, LE3 9QP
Dr Anvesha Singh
- Recruiting
Lincoln County Hospital
Lincoln, LN2 5QY
Dr Kelvin Lee
- Recruiting
Royal Liverpool Hospital
Liverpool, Merseyside, L7 8YE
Prathap Kanagala
- Recruiting
Liverpool Heart and Chest Hospital
Liverpool, L14 3PE
Dr Timothy Fairbairn
- Not yet recruiting
Royal Liverpool Hospital
Liverpool, L7 8XP
Dr Prathap Kanagala
Dr Michael Fisher
- Recruiting
St Bartholomew's Hospital
London, EC1A 7BE
Dr Thomas Treibel
- Recruiting
St Thomas' Hospital
London, SE1 7EH
Professor Ronak Rajani
- Recruiting
University Hospital Lewisham
London, SE13 6LH
Dr Amar Singh
- Recruiting
Chelsea and Westminster Hospital
London, SW10 9NH
Dr Gajen Sunthar Kanaganayagam
- Recruiting
St George's Hospital
London, SW17 0QT
Dr Sami Firoozi
- Recruiting
Cleveland Clinic London Hospital
London, SW1X 7HY
Dr Guy Llyod
- Recruiting
Imperial College Healthcare NHS Trust
London
Professor Jamil Mayet
- Recruiting
Maidstone & Tunbridge Wells Hospital
Maidstone, ME16 9QQ
Dr Timothy Williams
- Recruiting
Wythenshawe Hospital
Manchester, M23 9LT
Dr Laura Dobson
- Recruiting
North Manchester General Hospital
Manchester, M8 5RB
Dr Laura Dobson
Dr Ahmed Adlan
- Recruiting
The James Cook University Hospital
Middlesbrough, TS4 3BW
Dr Jeet Thambyrajah
- Recruiting
Freeman Hospital
Newcastle upon Tyne, NE7 7DN
Professor Vijay Kunadian
- Recruiting
Norfolk and Norwich University Hospital
Norwich, Norfolk, NR4 7UY
Dr Vassilios Vassiliou
- Recruiting
Kings Mill Hospital
Nottingham, NG17 4JL
Dr Thandar Aye
- Recruiting
Queens Medical Centre
Nottingham, NG7 2UH
Dr Michael Sosin
- Recruiting
George Eliot Hospital
Nuneaton, West Midlands, CV10 7DJ
Suresh Krishnamoorthy
- Recruiting
Royal Alexandra Hospital
Paisley, PA2 9PN
Dr Stuart Hood
- Recruiting
Derriford Hospital
Plymouth, PL6 8DH
Dr Sivasankar Sangaraju
Mr Sanjay Asopa
- Recruiting
Poole Hospital
Poole, BH15 2JB
Dr Chris Steadman
- Recruiting
Queen Alexandra Hospital
Portsmouth, PO6 3LY
Dr Peter Haworth
- Recruiting
Scunthorpe General Hospital
Scunthorpe, North Lincolnshire, DN15 7BH
Rashed Hossain
- Recruiting
Northern General Hospital
Sheffield, S5 7AU
Dr Muhhammad Aetesam-ur-Rahman
- Recruiting
Southampton General Hospital
Southampton, SO16 6YD
Professor Nick Curzen
Mr Sunil Ohri
- Recruiting
Forth Valley Royal Hospital
Stirling, FK9 4SW
Dr Christopher Gingles
- Recruiting
Stepping Hill Hospital
Stockport, SK2 7JE
Dr Rosica Panayotova
- Recruiting
North Tees and Hartlepool NHS Foundation Trust
Stockton-on-Tees, TS19 8PE
Dr Paul Davison
- Recruiting
South Tyneside and Sunderland NHS Foundation Trust
Sunderland
Samuel McClure
- Recruiting
Morriston Hospital
Swansea, Wales, SA6 6NL
Alexander Chase
- Recruiting
Musgrove Park Hospital
Taunton, Somerset, TA1 5DA
Thomas Rees
- Recruiting
Torbay Hospital
Torquay, TQ2 7AA
Dr Usman Sheikh
- Recruiting
Royal Cornwall Hospital
Truro, TR1 3LJ
Dr Mohammed Abubakr
- Recruiting
Pinderfields Hospital
Wakefield, WF1 4DG
Dr Thomas Craven
- Recruiting
Walsall Manor Hospital
Walsall, West Midlands, WS2 9PS
Rumi Jaumdally
- Recruiting
South Warwickshire University NHS Foundation Trust
Warwick
Dr John Fryearson
- Recruiting
Watford General Hospital
Watford, WD18 0HB
Dr Piyush Jain
- Recruiting
Sandwell General Hospital
West Bromwich, West Midlands, B71 4HJ
Abdul Maher
- Recruiting
New Cross Hospital
Wolverhampton
Sandeep Hothi
- Recruiting
Worcester Acute Hospitals NHS FT
Worcester
Ashiq Saffy
- Withdrawn
Yeovil District Hospital
Yeovil, BA21 4AT
Australia20 sites, 20 recruiting
- Recruiting
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Dr Jerrett Lau
- Recruiting
Flinders Medical Centre
Adelaide, South Australia, SA 5042
Professor Joseph Selvanayagam
- Recruiting
Prince Charles Hospital
Chermside, Queensland, 4032
Dale Murdoch
- Recruiting
Monash Health
Clayton, Victoria, 3168
Professor Julian Smith
- Recruiting
Townsville Hospital
Douglas, Queensland, 4814
Dr Lim Eng
- Recruiting
Lyell McEwin Hospital
Elizabeth Vale, SA 5112
Dr Luan Huynh
- Recruiting
Northern Hospital
Epping, VIC 3076
Dr Chiew Wong
- Recruiting
Canberra Hospital
Garran, Australian Capital Territory, 2605
Professor Walter Abhayaratna
- Recruiting
University Hospital Geelong
Geelong, Victoria, 3220
A/Professor John Amerena
- Recruiting
Royal Hobart Hospital
Hobart, TAS 7000
Dr Ashutosh Hardikar
- Recruiting
Nepean Hospital
Kingswood, NSW 2747
Professor Kaz Negishi
- Recruiting
Liverpool Hospital
Liverpool, New South Wales, 2170
Professor Dominic Leung
- Recruiting
John Hunter Hospital
New Lambton Heights, NSW 2305
A/Professor Aaron Sverdlov
- Recruiting
Fiona Stanley Hospital
Perth, Western Australia, 6150
Dr Gerald Yong
- Recruiting
Royal Perth Hospital
Perth, Western Australia, WA6000
Professor Graham Hillis
- Recruiting
The Gold Coast Hospital
Southport, Queensland, 4215
Dr Kuljit Singh
- Recruiting
Royal North Shore Hospital
St Leonards, New South Wales, 2065
Professor Ravinay Bhindi
- Recruiting
Royal Darwin Hospital
Tiwi, TIWI NT 0810
Dr Hussam Tayeb
- Recruiting
Westmead Hospital
Westmead, New South Wales, 2145
Dr Dylan Wynne
- Recruiting
Wollongong Hospital
Wollongong, New South Wales, 2500
Dr Edward Danson
Belgium3 sites, 3 recruiting
- Recruiting
Sint-Jan Hospital
Bruges, Brugge, 8000
Dr Philippe Debonnaire
- Recruiting
Ziekenhuis Oost-Limburg
Genk, 3600
Dr Philippe Bertrand
- Recruiting
University Hospital of Brussels
Jette, 1090
Dr Xavier Galloo
New Zealand3 sites, 3 recruiting
- Recruiting
Auckland City Hospital
Auckland, 1023
Professor Ralph Stewart
- Recruiting
Christchurch Hospital
Christchurch, 8011
Dr Philip Adamson
- Recruiting
Dunedin Hospital
Dunedin, 9016
Dr Sean Coffey
Netherlands2 sites, 2 recruiting
- Recruiting
Frisius Medical Center
Leeuwarden
Olga Bondarenko
- Recruiting
Radboud University Medical Center
Nijmegen
Saloua ElMessaoudi
Spain2 sites, 2 recruiting
- Recruiting
Hospital Germans Trias
Barcelona
Dr Victoria Delgado
- Recruiting
University Hospital of Navarra
Pamplona
Rafael Sadaba
Serbia1 site, 1 recruiting
- Recruiting
Institute of Cardiovascular Diseases
Kamenitz, 21204
Lazar Velicki
About this study
Official title: A Randomised Controlled Trial of Early Valve Replacement in Severe ASYmptomatic Aortic Stenosis
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.
Read the detailed description
This is a major pragmatic multi-centre prospective parallel group open RCT. It will be conducted in the UK, Australia and New Zealand, funding is being sought in several countries to expand recruitment internationally. The study is in 2 phases: the vanguard and main phase. Therefore the study will run an internal pilot to prove recruitment of the relevant number of participants during the initial 2 years.
The over-arching aim is to determine whether early AVR results in better clinical outcomes and cost-effectiveness than a strategy of expectant management in asymptomatic patients with severe AS.
The primary hypothesis is that early AVR or TAVI in asymptomatic patients with severe AS will result in a reduction in the composite primary outcome of cardiovascular (CV) death and hospitalisation for heart failure (HHF) when compared to the conventional approach of expectant management.
Potential participants will be identified by a member of the clinical care team following diagnosis with severe AS. Participants will be screened for eligibility using pre-specified inclusion/exclusion criteria. Eligible participants will be provided with a written version of the participant information sheet detailing the exact nature of the study, what it will involve for the participant and any risks involved with taking part. Participants will be given at least 24 hours to consider the information and decide whether or not to take part. The study will randomise up to 2104 patients with severe asymptomatic AS to either allocated expectant management OR aortic valve replacement. Participants randomised to AVR will be placed on a waiting list with the aim that surgery will be performed within 6 months, dependent on local hospitals' waiting lists. Participants randomised to AVR will undergo routine tests/procedures which may include coronary angiography. If the outcome of the coronary angiography reveals coronary heart disease, the decision to perform CABG or PCI will be made by the responsible cardiac surgeon and cardiologist, in consultation with the patient. All analyses will be undertaken using the principles of intention-to-treat with participants analysed in the group they were randomised regardless of treatment received.
EASY-AS is collaborating with the EVoLVeD study (Early Valve Replacement guided by Biomarkers of Left Ventricular Decompensation in Asymptomatic Patients with Severe Aortic Stenosis, Clinical Trials.gov NCT03094143). In centres where both EASY-AS and EVoLVeD are running, participants in EASY-AS will be offered the opportunity to take part in EVoLVeD.
Funding has been granted by the British Heart Foundation (UK), Medical Research Future Fund (Aus) and Heart Foundation (NZ). The UK sponsor is the University of Leicester. Additional support and resources for the study will be provided by the participating Trusts and their corresponding Clinical Research Networks in the UK. The central co-ordination centre is the University of Leicester Clinical Trials Unit.
- Conditions
- Aortic Stenosis
- Being tested
- Aortic valve replacement
- Keywords
- Asymptomatic aortic stenosis, Aortic valve replacement, Randomised controlled trial, Expectant management, Hospitalisation for heart failure, Cardiovascular death
- Medical subject headings
- Aortic Valve Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aortic valve replacementProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Group A: Aortic valve replacement | Active comparator | 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 6 months, dependent on local hospitals' waiting lists. Receives: Procedure: Aortic valve replacement |
| Group B: Expectant management | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Combined measure of cardiovascular death, hospitalisation for heart failure and Stroke.
Measured in days from randomisation until end of trial (minimum 3 years).
The primary analysis will be undertaken when the last recruited participant has had 3 years follow-up or 601 events have accrued at an annual extraction (whichever is first), which is estimated to be after a median of 5.5 years follow-up assuming 2104 patients are recruited by September 2027.
Measured: Through study completion, median 5.5 years
Secondary outcomes (7)
WHO Disability Assessment Schedule (WHODAS 2.0)
Assessing disability-free survival during the period of active recruitment.
Scores assigned to each of the items - "none" (0), "mild" (1) "moderate" (2), "severe" (3) and "extreme" (4) - are summed. The simple sum of the scores of the items across all domains constitutes a statistic that is sufficient to describe the degree of functional limitations.
Step 1 - Summing of recoded item scores within each domain. Step 2 - Summing of all six domain scores. Step 3 - Converting the summary score into a metric ranging from 0 to 100 (where 0 = no disability; 100 = full disability).
Measured: 6, 12, 24 and 36 months
NHS record linkage services
Assessing number of days alive and out of hospital.
All participants will be consented for long-term follow-up (10 years) and clinical events will be ascertained through NHS Digital or equivalent.
Measured: Up to 5 years
Death (cardiovascular, including sudden cardiac death, and non-cardiovascular), hospitalisation for heart failure, myocardial infarction, stroke
Assessing number of major adverse events.
All participants will be consented for long-term follow-up (10 years) and clinical events will be ascertained through NHS Digital or equivalent.
Measured: 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
Assessing additional outcomes of special interest.
All participants will be consented for long-term follow-up (10 years) and clinical events will be ascertained through NHS Digital or equivalent.
Measured: Up to 5 years
EuroQol five-level (EQ-5D-5L) questionnaire
Assessing quality of life during the period of active recruitment.
EQ-5D-5L has 2 components: health state description and evaluation. In the description part, health status is measured in terms of 5 dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Mobility dimension asks about the person's walking ability. Self-care dimension asks about the ability to wash or dress by oneself, and usual activities dimension measures performance in "work, study, housework, family or leisure activities". In pain/discomfort dimension, it asks how much pain or discomfort they have, and in anxiety/depression dimension, it asks how anxious or depressed they are. The respondents self-rate their level of severity for each dimension using a 5-level scale.
Measured: 6, 12, 24 and 36 months
Health Economics Questionnaire
Assessed using self-reported health care resource use and cost effectiveness.
Participants will be asked if they have used any of the following services at a hospital for reasons that may be related to their heart condition or treatment: hospital services, services in the community and specialist equipment.
The data from this questionnaire will be scored by a Health Economist at the end of the study.
Measured: 6, 12, 24 and 36 months
Edmonton Frail Scale (EFS) (Bedside and Acute Care Version)
Assessing frailty at baseline using a simple tool to assess frailty in older patients. It consists of nine domains and eleven items, each scoring 0 points (frailty absent or normal health), 1 point (minor errors or mild/moderate impairment), or 2 points (important errors or severely impaired).
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2019
- Study start10 Mar 2020
- Primary completion1 Apr 2031 (estimated)
- Study completion1 Apr 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Aortic StenosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2,104 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Leicester
- Sponsor type
- University, hospital or other
- Collaborators
- University of Auckland, New Zealand, University Hospitals, Leicester, The University of Western Australia
- Responsible party
- Sponsor
- Investigators
- Gerry McCann, Prof, Principal investigator, University of LeicesterGraham Hillis, Prof, Principal investigator, The University of Western AustraliaRalph Stewart, Prof, Principal investigator, University of Aukland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04204915
- Sponsor's protocol ID
- 0700
- Other IDs
- CS/18/7/33714, 266292, 90865, 0700
- Acronym
- EASY-AS
- Status last verified
- Sep 2025
- First submitted
- 17 Dec 2019
- Last updated
- 21 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 41571417Richardson C, Gilbert T, Aslam S, Brookes CL, Singh A, Newby DE, Dweck MR, Stewart RAH, Myles PS, Briffa T, Selvanayagam J, Chow CK, Murphy GJ, Akowuah EF, Lord J, Barber S, Paola ASD, McCann GP, Hillis GS. Rationale and design of the early valve replacement in severe asymptomatic aortic stenosis trial. Am Heart J. 2024 Sep;275:119-127. doi: 10.1016/j.ahj.2024.05.013. Epub 2024 May 30.
PubMed 38821453
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Controlled Trial of Early Valve Replacement in Severe ASYmptomatic Aortic Stenosis
- ClinicalTrials.gov ID
- NCT04204915
- Acronym / sponsor ID
- EASY-AS / 0700
- Conditions
- Aortic Stenosis
- Keywords
- Asymptomatic aortic stenosis, Aortic valve replacement, Randomised controlled trial, Expectant management, Hospitalisation for heart failure, Cardiovascular death
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 2,104 participants (estimated)
- Lead sponsor
- University of LeicesterUniversity, hospital or other
- Collaborators
- University of Auckland, New Zealand, University Hospitals, Leicester, The University of Western Australia
- Study start
- 10 Mar 2020 (actual)
- Primary completion
- 1 Apr 2031 (estimated)
- Study completion
- 1 Apr 2031 (estimated)
- First posted
- 19 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a major pragmatic multi-centre prospective parallel group open RCT. It will be conducted in the UK, Australia and New Zealand, funding is being sought in several countries to expand recruitment internationally. The study is in 2 phases: the vanguard and main phase. Therefore the study will run an internal pilot to prove recruitment of the relevant number of participants during the initial 2 years.
The over-arching aim is to determine whether early AVR results in better clinical outcomes and cost-effectiveness than a strategy of expectant management in asymptomatic patients with severe AS.
The primary hypothesis is that early AVR or TAVI in asymptomatic patients with severe AS will result in a reduction in the composite primary outcome of cardiovascular (CV) death and hospitalisation for heart failure (HHF) when compared to the conventional approach of expectant management.
Potential participants will be identified by a member of the clinical care team following diagnosis with severe AS. Participants will be screened for eligibility using pre-specified inclusion/exclusion criteria. Eligible participants will be provided with a written version of the participant information sheet detailing the exact nature of the study, what it will involve for the participant and any risks involved with taking part. Participants will be given at least 24 hours to consider the information and decide whether or not to take part. The study will randomise up to 2104 patients with severe asymptomatic AS to either allocated expectant management OR aortic valve replacement. Participants randomised to AVR will be placed on a waiting list with the aim that surgery will be performed within 6 months, dependent on local hospitals' waiting lists. Participants randomised to AVR will undergo routine tests/procedures which may include coronary angiography. If the outcome of the coronary angiography reveals coronary heart disease, the decision to perform CABG or PCI will be made by the responsible cardiac surgeon and cardiologist, in consultation with the patient. All analyses will be undertaken using the principles of intention-to-treat with participants analysed in the group they were randomised regardless of treatment received.
EASY-AS is collaborating with the EVoLVeD study (Early Valve Replacement guided by Biomarkers of Left Ventricular Decompensation in Asymptomatic Patients with Severe Aortic Stenosis, Clinical Trials.gov NCT03094143). In centres where both EASY-AS and EVoLVeD are running, participants in EASY-AS will be offered the opportunity to take part in EVoLVeD.
Funding has been granted by the British Heart Foundation (UK), Medical Research Future Fund (Aus) and Heart Foundation (NZ). The UK sponsor is the University of Leicester. Additional support and resources for the study will be provided by the participating Trusts and their corresponding Clinical Research Networks in the UK. The central co-ordination centre is the University of Leicester Clinical Trials Unit.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A: Aortic valve replacement | Active comparator | Procedure: Aortic valve replacementParticipants 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 6 months, dependent on local hospitals' waiting lists. |
| Group B: Expectant management | No intervention | –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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age >18 years
- Patient has severe asymptomatic AS, in line with current international guidelines, defined as either:
- 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
Key exclusion criteria (7 listed)
- Symptoms related to AS
- Additional severe valvular heart disease
- Other cardiac surgery planned pre-randomisation (eg CABG)
- Left ventricular systolic dysfunction (LVEF <50%)
- Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aortic valve replacementParticipants 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. | Procedure or surgery | Group A: Aortic valve replacement |
Primary outcome
Combined measure of cardiovascular death, hospitalisation for heart failure and Stroke.
Time frame: Through study completion, median 5.5 years
Measured in days from randomisation until end of trial (minimum 3 years). The primary analysis will be undertaken when the last recruited participant has had 3 years follow-up or 601 events have accrued at an annual extraction (whichever is first), which is estimated to be after a median of 5.5 years follow-up assuming 2104 patients are recruited by September 2027.
7 secondary outcomes
WHO Disability Assessment Schedule (WHODAS 2.0)
Time frame: 6, 12, 24 and 36 months
NHS record linkage services
Time frame: Up to 5 years
Death (cardiovascular, including sudden cardiac death, and non-cardiovascular), hospitalisation for heart failure, myocardial infarction, stroke
Time frame: 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
Time frame: Up to 5 years
EuroQol five-level (EQ-5D-5L) questionnaire
Time frame: 6, 12, 24 and 36 months
Health Economics Questionnaire
Time frame: 6, 12, 24 and 36 months
Edmonton Frail Scale (EFS) (Bedside and Acute Care Version)
Time frame: Baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2026.
- Derived from this study: PubMed 41571417Allmark 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.
- Derived from this study: PubMed 38821453Richardson C, Gilbert T, Aslam S, Brookes CL, Singh A, Newby DE, Dweck MR, Stewart RAH, Myles PS, Briffa T, Selvanayagam J, Chow CK, Murphy GJ, Akowuah EF, Lord J, Barber S, Paola ASD, McCann GP, Hillis GS. Rationale and design of the early valve replacement in severe asymptomatic aortic stenosis trial. Am Heart J. 2024 Sep;275:119-127. doi: 10.1016/j.ahj.2024.05.013. Epub 2024 May 30.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Michael Walters contact
Gerry McCann, Prof principal investigator
University of Leicester
Graham Hillis, Prof principal investigator
The University of Western Australia
Ralph Stewart, Prof principal investigator
University of Aukland
110 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Aortic valve replacement in people with Aortic Stenosis, run by University of Leicester at 110 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 110 sites in United Kingdom, Australia, Belgium, New Zealand, Netherlands and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Carla Richardson (+44 0116-229-7936 ext. 7936, easyas@leicester.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Combined measure of cardiovascular death, hospitalisation for heart failure and Stroke. (time frame: Through study completion, median 5.5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04204915, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2026.