A Randomised Controlled Trial of Early Valve Replacement in Severe ASYmptomatic Aortic Stenosis
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 2,104
- 试验地点
- 204
- 主要终点
- Combined measure of cardiovascular death and hospitalisation for heart failure
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •Symptoms related to AS
- •Additional severe valvular heart disease
- •Other cardiac surgery planned pre-randomisation (eg CABG)
- •Left ventricular systolic dysfunction (LVEF <50%)
- •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
研究组 & 干预措施
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 6 months, dependent on local hospitals' waiting lists.
干预措施: Aortic valve replacement (Procedure)
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.
结局指标
主要结局
Combined measure of cardiovascular death and hospitalisation for heart failure
时间窗: Minimum 3 years
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.
Combined measure of cardiovascular death, hospitalisation for heart failure and Stroke.
时间窗: 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.
次要结局
- Death (cardiovascular, including sudden cardiac death, and non-cardiovascular), hospitalisation for heart failure, myocardial infarction, stroke(Up to 5 years)
- WHO Disability Assessment Schedule (WHODAS 2.0)(6, 12, 24 and 36 months)
- Health Economics Questionnaire(6, 12, 24 and 36 months)
- NHS record linkage services(Up to 5 years)
- Edmonton Frail Scale (EFS) (Bedside and Acute Care Version)(Baseline)
- EuroQol five-level (EQ-5D-5L) questionnaire(6, 12, 24 and 36 months)
- 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)