The Early Valve Replacement in Severe ASYmptomatic Aortic Stenosis Study
ConditionAortic Stenosis
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Leicester
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age >18 years
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
Disqualifiers
Symptoms related to AS
Additional severe valvular heart disease
Other cardiac surgery planned pre-randomisation (eg CABG)
Left ventricular systolic dysfunction (LVEF <50%)
Trial design
Design model
Parallel
Treatments tested in this trial
Aortic valve replacement
Procedure/SurgeryParticipants 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.
Treatment groups
2,104 Participants
are divided into 2 treatment groupsGroup A: Group A: Aortic valve replacementActive comparator 1 intervention
Group B: Group B: Expectant managementNo intervention 0 interventions
Trial outcomes
Primary outcomes
1
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.
Time frame
Through study completion, median 5.5 yearsSecondary outcomes
1
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).
Time frame
6, 12, 24 and 36 months2
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.
Time frame
Up to 5 years3
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.
Time frame
Up to 5 years4
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.
Time frame
Up to 5 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
University of Leicester
Lead sponsor
University of Auckland, New Zealand
Collaborator
University Hospitals, Leicester
Collaborator
The University of Western Australia
Collaborator
Source ClinicalTrials.gov