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

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.

Study Overview

• Status: Recruiting
• Conditions: Aortic Stenosis
• Intervention / Treatment: Procedure: Aortic valve replacement

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 2844 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 3 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 Type: Interventional
• Enrollment (Estimated): 2844
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michael Walters; Email: easyas@leicester.ac.uk
• Study Contact Backup: Name: Carla Richardson; Phone Number: 7936 +44 0116-229-7936; Email: easyas@leicester.ac.uk

Study Locations

• Australia
  • Elizabeth Vale, Australia, SA 5112
    • Recruiting
    • Lyell McEwin Hospital
    • Contact: Dr Luan Huynh
  • Epping, Australia, VIC 3076
    • Recruiting
    • Northern Hospital
    • Contact: Dr Chiew Wong
  • Hobart, Australia, TAS 7000
    • Recruiting
    • Royal Hobart Hospital
    • Contact: Dr Ashutosh Hardikar
  • Kingswood, Australia, NSW 2747
    • Recruiting
    • Nepean Hospital
    • Contact: Professor Kaz Negishi
  • New Lambton Heights, Australia, NSW 2305
    • Recruiting
    • John Hunter Hospital
    • Contact: A/Professor Aaron Sverdlov
  • Tiwi, Australia, TIWI NT 0810
    • Recruiting
    • Royal Darwin Hospital
    • Contact: Dr Hussam Tayeb
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2605
      • Recruiting
      • Canberra Hospital
      • Contact: Professor Walter Abhayaratna
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Recruiting
      • Liverpool Hospital
      • Contact: Professor Dominic Leung
    • St Leonards, New South Wales, Australia, 2065
      • Recruiting
      • Royal North Shore Hospital
      • Contact: Professor Ravinay Bhindi
    • Westmead, New South Wales, Australia, 2145
      • Recruiting
      • Westmead Hospital
      • Contact: Dr Dylan Wynne
    • Wollongong, New South Wales, Australia, 2500
      • Recruiting
      • Wollongong Hospital
      • Contact: Dr Edward Danson
  • Queensland
    • Chermside, Queensland, Australia, 4032
      • Recruiting
      • Prince Charles Hospital
      • Contact: Dale Murdoch
    • Douglas, Queensland, Australia, 4814
      • Recruiting
      • Townsville Hospital
      • Contact: Dr Lim Eng
    • Southport, Queensland, Australia, 4215
      • Recruiting
      • The Gold Coast Hospital
      • Contact: Dr Kuljit Singh
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • Royal Adelaide Hospital
      • Contact: Dr Jerrett Lau
    • Adelaide, South Australia, Australia, SA 5042
      • Recruiting
      • Flinders Medical Centre
      • Contact: Professor Joseph Selvanayagam
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Recruiting
      • Monash Health
      • Contact: Professor Julian Smith
    • Geelong, Victoria, Australia, 3220
      • Recruiting
      • University Hospital Geelong
      • Contact: A/Professor John Amerena
  • Western Australia
    • Perth, Western Australia, Australia, 6150
      • Recruiting
      • Fiona Stanley Hospital
      • Contact: Dr Gerald Yong
    • Perth, Western Australia, Australia, WA6000
      • Recruiting
      • Royal Perth Hospital
      • Contact: Professor Graham Hillis
• Belgium
  • Bruges, Belgium, 8000
    • Recruiting
    • Sint-Jan Hospital
    • Contact: Dr Philippe Debonnaire
  • Genk, Belgium, 3600
    • Recruiting
    • Ziekenhuis Oost-Limburg
    • Contact: Dr Philippe Bertrand
  • Jette, Belgium, 1090
    • Recruiting
    • University Hospital of Brussels
    • Contact: Dr Xavier Galloo
• Netherlands
  • Leeuwarden, Netherlands
    • Recruiting
    • Frisius Medical Center
    • Contact: Olga Bondarenko
  • Nijmegen, Netherlands
    • Recruiting
    • Radboud University Medical Center
    • Contact: Saloua ElMessaoudi
• New Zealand
  • Auckland, New Zealand, 1023
    • Recruiting
    • Auckland City Hospital
    • Contact: Professor Ralph Stewart
  • Christchurch, New Zealand, 8011
    • Recruiting
    • Christchurch Hospital
    • Contact: Dr Philip Adamson
  • Dunedin, New Zealand, 9016
    • Recruiting
    • Dunedin Hospital
    • Contact: Dr Sean Coffey
• Serbia
  • Kamenitz, Serbia, 21204
    • Recruiting
    • Institute of Cardiovascular Diseases
    • Contact: Lazar Velicki
• Spain
  • Barcelona, Spain
    • Recruiting
    • Hospital Germans Trias
    • Contact: Dr Victoria Delgado
  • Pamplona, Spain
    • Recruiting
    • University Hospital of Navarra
    • Contact: Rafael Sádaba
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
    • Recruiting
    • Aberdeen Royal Infirmary
    • Contact: Dr Ciprian Dospinescu
    • Contact: Mr Hussein El-Shafei
  • Aintree, United Kingdom, L9 7AL
    • Recruiting
    • Aintree University Hospital
    • Contact: Dr Prathap Kanagala
  • Ayr, United Kingdom, KA6 6DX
    • Recruiting
    • University Hospital Ayr
    • Contact: Dr Jim McGowan
  • Barnsley, United Kingdom
    • Recruiting
    • Barnsley Hospital NHS Foundation Trust
    • Contact: Deoraj Zamfar
  • Basildon, United Kingdom, SS16 5NL
    • Recruiting
    • Basildon University Hospital
    • Contact: Dr Jason Dungu
  • Birmingham, United Kingdom, B15 2GW
    • Recruiting
    • Queen Elizabeth Hospital
    • Contact: Professor Rick Steeds
  • Blackpool, United Kingdom, FY3 8NR
    • Recruiting
    • Blackpool Victoria Hospital
    • Contact: Professor Nidal Bittar
  • Brighton, United Kingdom, BN2 5BE
    • Recruiting
    • Royal Sussex County Hospital
    • Contact: Dr David Hildick-Smith
  • Carlisle, United Kingdom, CA2 7AF
    • Recruiting
    • North Cumbria Integrated Care
    • Contact: Dr Rhidian Shelton
  • Chesterfield, United Kingdom, S44 5BL
    • Recruiting
    • Chesterfield Royal Hospital
    • Contact: Dr Justin Cooke
  • Coventry, United Kingdom, CV2 2DX
    • Recruiting
    • University Hospital Coventry & Warwickshire
    • Contact: Dr Luke Tapp
    • Contact: Dr Jamal Khan
  • Darlington, United Kingdom, DL3 6HX
    • Recruiting
    • County Durham and Darlington NHS Foundation Trust
    • Contact: Dr Darragh Twomey
  • Doncaster, United Kingdom, DN2 5LT
    • Recruiting
    • Doncaster Royal Infirmary
    • Contact: Dr Gillian Payne
  • Dundee, United Kingdom
    • Recruiting
    • Ninewells Hospital
    • Contact: Chim Lang
  • Edinburgh, United Kingdom, EH16 4SA
    • Recruiting
    • The Royal Infirmary of Edinburgh
    • Contact: Professor Marc Dweck
    • Contact: Professor David Newby
  • Exeter, United Kingdom, EX2 5DW
    • Recruiting
    • Royal Devon & Exeter Hospital
    • Contact: Dr Andrew Ludman
  • Gateshead, United Kingdom, NE9 6SX
    • Recruiting
    • Gateshead Health NHS Foundation Trust
    • Contact: Dr Ashfaq Mohammed
  • Glasgow, United Kingdom
    • Recruiting
    • Queen Elizabeth University Hospital
    • Contact: Fraser Graham
  • Glasgow, United Kingdom
    • Recruiting
    • Glasgow Royal Infirmary
    • Contact: Dr Stuart Watkins
  • Glasgow, United Kingdom, G81 4DY
    • Recruiting
    • Golden Jubilee National Hospital
    • Contact: Dr Nawwar Al-Attar
  • Gloucester, United Kingdom
    • Recruiting
    • Gloucestershire Hospitals NHS Foundation
    • Contact: Val Nikolaidou
  • Huddersfield, United Kingdom, HD3 3EA
    • Recruiting
    • Huddersfield Royal Infirmary
    • Contact: Dr Hossam El Mahy
  • Isleworth, United Kingdom, TW7 6AF
    • Recruiting
    • West Middlesex University Hospital
    • Contact: Dr Gajen Sunthar Kanaganayagam
  • Keighley, United Kingdom, BD20 6TD
    • Recruiting
    • Airedale General Hospital
    • Contact: Dr Haqeel Jamil
  • Kilmarnock, United Kingdom, KA2 0BE
    • Recruiting
    • University Hospital Crosshouse
    • Contact: Dr Angie Ghattas
  • Leeds, United Kingdom, LS1 3EX
    • Recruiting
    • Leeds General Infirmary
    • Contact: Professor John Greenwood
  • Lincoln, United Kingdom, LN2 5QY
    • Recruiting
    • Lincoln County Hospital
    • Contact: Dr Kelvin Lee
  • Liverpool, United Kingdom, L14 3PE
    • Recruiting
    • Liverpool Heart and Chest Hospital
    • Contact: Dr Timothy Fairbairn
  • Liverpool, United Kingdom, L7 8XP
    • Not yet recruiting
    • Royal Liverpool Hospital
    • Contact: Dr Prathap Kanagala
    • Contact: Dr Michael Fisher
  • London, United Kingdom, EC1A 7BE
    • Recruiting
    • St Bartholomew's Hospital
    • Contact: Dr Thomas Treibel
  • London, United Kingdom, SE1 7EH
    • Recruiting
    • St Thomas' Hospital
    • Contact: Professor Ronak Rajani
  • London, United Kingdom
    • Recruiting
    • Imperial College Healthcare NHS Trust
    • Contact: Professor Jamil Mayet
  • London, United Kingdom, SW17 0QT
    • Recruiting
    • St George's Hospital
    • Contact: Dr Sami Firoozi
  • London, United Kingdom, SW10 9NH
    • Recruiting
    • Chelsea and Westminster Hospital
    • Contact: Dr Gajen Sunthar Kanaganayagam
  • London, United Kingdom, SE13 6LH
    • Recruiting
    • University Hospital Lewisham
    • Contact: Dr Amar Singh
  • London, United Kingdom, SW1X 7HY
    • Recruiting
    • Cleveland Clinic London Hospital
    • Contact: Dr Guy Llyod
  • Maidstone, United Kingdom, ME16 9QQ
    • Recruiting
    • Maidstone & Tunbridge Wells Hospital
    • Contact: Dr Timothy Williams
  • Manchester, United Kingdom, M23 9LT
    • Recruiting
    • Wythenshawe Hospital
    • Contact: Dr Laura Dobson
  • Manchester, United Kingdom, M8 5RB
    • Recruiting
    • North Manchester General Hospital
    • Contact: Dr Laura Dobson
    • Contact: Dr Ahmed Adlan
  • Middlesbrough, United Kingdom, TS4 3BW
    • Recruiting
    • The James Cook University Hospital
    • Contact: Dr Jeet Thambyrajah
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Recruiting
    • Freeman Hospital
    • Contact: Professor Vijay Kunadian
  • Nottingham, United Kingdom, NG7 2UH
    • Recruiting
    • Queens Medical Centre
    • Contact: Dr Michael Sosin
  • Nottingham, United Kingdom, NG17 4JL
    • Recruiting
    • Kings Mill Hospital
    • Contact: Dr Thandar Aye
  • Paisley, United Kingdom, PA2 9PN
    • Recruiting
    • Royal Alexandra Hospital
    • Contact: Dr Stuart Hood
  • Plymouth, United Kingdom, PL6 8DH
    • Recruiting
    • Derriford Hospital
    • Contact: Dr Sivasankar Sangaraju
    • Contact: Mr Sanjay Asopa
  • Poole, United Kingdom, BH15 2JB
    • Recruiting
    • Poole Hospital
    • Contact: Dr Chris Steadman
  • Portsmouth, United Kingdom, PO6 3LY
    • Recruiting
    • Queen Alexandra Hospital
    • Contact: Dr Peter Haworth
  • Sheffield, United Kingdom, S5 7AU
    • Recruiting
    • Northern General Hospital
    • Contact: Dr Muhhammad Aetesam-ur-Rahman
  • Southampton, United Kingdom, SO16 6YD
    • Recruiting
    • Southampton General Hospital
    • Contact: Professor Nick Curzen
    • Contact: Mr Sunil Ohri
  • Stirling, United Kingdom, FK9 4SW
    • Recruiting
    • Forth Valley Royal Hospital
    • Contact: Dr Christopher Gingles
  • Stockport, United Kingdom, SK2 7JE
    • Recruiting
    • Stepping Hill Hospital
    • Contact: Dr Rosica Panayotova
  • Stockton-on-Tees, United Kingdom, TS19 8PE
    • Recruiting
    • North Tees and Hartlepool NHS Foundation Trust
    • Contact: Dr Paul Davison
  • Sunderland, United Kingdom
    • Recruiting
    • South Tyneside and Sunderland NHS Foundation Trust
    • Contact: Samuel McClure
  • Torquay, United Kingdom, TQ2 7AA
    • Recruiting
    • Torbay Hospital
    • Contact: Dr Usman Sheikh
  • Truro, United Kingdom, TR1 3LJ
    • Recruiting
    • Royal Cornwall Hospital
    • Contact: Dr Mohammed Abubakr
  • Wakefield, United Kingdom, WF1 4DG
    • Recruiting
    • Pinderfields Hospital
    • Contact: Dr Thomas Craven
  • Warwick, United Kingdom
    • Recruiting
    • South Warwickshire University NHS Foundation Trust
    • Contact: Dr John Fryearson
  • Watford, United Kingdom, WD18 0HB
    • Recruiting
    • Watford General Hospital
    • Contact: Dr Piyush Jain
  • Wolverhampton, United Kingdom
    • Recruiting
    • New Cross Hospital
    • Contact: Sandeep Hothi
  • Worcester, United Kingdom
    • Recruiting
    • Worcester Acute Hospitals NHS FT
    • Contact: Ashiq Saffy
  • Yeovil, United Kingdom, BA21 4AT
    • Withdrawn
    • Yeovil District Hospital
  • County Durham
    • Durham, County Durham, United Kingdom, DH1 5TW
      • Recruiting
      • University Hospital of North Durham
      • Contact: Darragh Twomey
  • Denbighshire
    • Bodelwyddan, Denbighshire, United Kingdom, LL18 5UJ
      • Recruiting
      • Glan Clwyd Hospital
      • Contact: Satheesh Nair
  • Dorset
    • Dorchester, Dorset, United Kingdom, DT1 2JY
      • Withdrawn
      • Dorset County Hospital
  • Hampshire
    • Basingstoke, Hampshire, United Kingdom, RG24 9NA
      • Recruiting
      • Basingstoke And North Hampshire Hospital
      • Contact: Dr Jason Glover
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE3 9QP
      • Recruiting
      • University Hospitals Leicester, Glenfield
      • Contact: Dr Anvesha Singh
  • Merseyside
    • Liverpool, Merseyside, United Kingdom, L7 8YE
      • Recruiting
      • Royal Liverpool Hospital
      • Contact: Prathap Kanagala
  • Norfolk
    • Norwich, Norfolk, United Kingdom, NR4 7UY
      • Recruiting
      • Norfolk and Norwich University Hospital
      • Contact: Dr Vassilios Vassiliou
  • North Lincolnshire
    • Scunthorpe, North Lincolnshire, United Kingdom, DN15 7BH
      • Recruiting
      • Scunthorpe General Hospital
      • Contact: Rashed Hossain
  • Northamptonshire
    • Kettering, Northamptonshire, United Kingdom, NN16 8UZ
      • Recruiting
      • Kettering General Hospital
      • Contact: Dr Kai Hogrefe
  • Northumberland
    • Ashington, Northumberland, United Kingdom, NE63 9JJ
      • Recruiting
      • Wansbeck General Hospital
      • Contact: Dr David Ripley
  • Scotland
    • Inverness, Scotland, United Kingdom, IV2 3UJ
      • Recruiting
      • Raigmore Hospital
      • Contact: Stephen Leslie
  • Somerset
    • Taunton, Somerset, United Kingdom, TA1 5DA
      • Recruiting
      • Musgrove Park Hospital
      • Contact: Thomas Rees
  • Wales
    • Swansea, Wales, United Kingdom, SA6 6NL
      • Recruiting
      • Morriston Hospital
      • Contact: Alexander Chase
  • West Midlands
    • Dudley, West Midlands, United Kingdom, DY1 2HQ
      • Recruiting
      • Russells Hall Hospital
      • Contact: Craig Barr
    • Nuneaton, West Midlands, United Kingdom, CV10 7DJ
      • Recruiting
      • George Eliot Hospital
      • Contact: Suresh Krishnamoorthy
    • Walsall, West Midlands, United Kingdom, WS2 9PS
      • Recruiting
      • Walsall Manor Hospital
      • Contact: Rumi Jaumdally
    • West Bromwich, West Midlands, United Kingdom, B71 4HJ
      • Recruiting
      • Sandwell General Hospital
      • Contact: Abdul Maher
  • Wycombe
    • High Wycombe, Wycombe, United Kingdom, HP11 2TT
      • Recruiting
      • Wycombe Hospital
      • Contact: Dr Piers Clifford

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

   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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Procedure: 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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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.	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.	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.	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.	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.	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).	Baseline

Collaborators and Investigators

• Sponsor: University of Leicester
• Collaborators: University Hospitals, Leicester; University of Auckland, New Zealand; The University of Western Australia
• Investigators: 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

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2020
• Primary Completion (Estimated): April 1, 2031
• Study Completion (Estimated): April 1, 2031

Study Registration Dates

• First Submitted: December 17, 2019
• First Submitted That Met QC Criteria: December 17, 2019
• First Posted (Actual): December 19, 2019

Study Record Updates

• Last Update Posted (Estimated): September 25, 2025
• Last Update Submitted That Met QC Criteria: September 24, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Randomised controlled trial; Cardiovascular death; Aortic valve replacement; Expectant management; Asymptomatic aortic stenosis; Hospitalisation for heart failure
• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Surgical Procedures, Operative; Cardiovascular Surgical Procedures; Cardiac Surgical Procedures; Thoracic Surgical Procedures; Prosthesis Implantation; Heart Valve Prosthesis Implantation; Transcatheter Aortic Valve Replacement
• Other Study ID Numbers: 0700 (Sponsor); CS/18/7/33714 (Other Grant/Funding Number: British Heart Foundation); 266292 (Other Identifier: IRAS); 90865 (Other Identifier: EDGE)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No