Early Valve Replacement Guided by Biomarkers of LV Decompensation in Asymptomatic Patients With Severe AS

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

1000 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-07-21

Study Completion Date

2032-06-30

Brief Summary

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Aortic stenosis is the most common valvular disease in the Western world. It is caused by progressive narrowing of the aortic valve leading to increased strain on the heart muscle which has to work increasingly hard to pump blood through the narrowed valve. Over time the heart muscle thickens to generate more force, but eventually the heart fails leading to death if the valve is not replaced with an operation. No medical treatments exist to stop or reverse the heart valve narrowing. Current clinical guidelines suggest that an operation should be performed only when symptoms develop or the heart muscle is visibly weak on cardiac ultrasound scanning. However, symptoms can be difficult to interpret and in many patients the heart muscle has become irreversibly damaged and the heart fails to recover following surgery.

Using MRI scans of the heart, the investigators have identified heart scarring which seems to develop as the heart muscle thickens. Several studies now show that people who have developed this scarring are more likely to suffer poor outcomes including death. The investigators have also identified clinical risks that predict the presence of scarring.

The investigators propose a study where patients with severe aortic stenosis but no indications for valve replacement as per current guidelines are assessed for those clinical risks. If a participant's risk of having scarring is higher they will undergo a cardiac MRI scan. If scarring is present participants will be randomised to routine clinical care, or referral for valve replacement surgery. Participants with no evidence of scarring will be randomised routine care with study follow or not. The investigators of this study hypothesize that early surgery will lead to fewer complications and reduced risk of death compared to standard care.

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Detailed Description

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Conditions

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Aortic Valve Stenosis Hypertrophy, Left Ventricular

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

\~1000 patients with asymptomatic severe aortic stenosis will be screened across the sites (this is how we have defined enrollment below). Patients at high risk of left ventricular decompensation based on high-sensitivity troponin or ECG will proceed to CMR. Participants are randomised based on the result of the cardiac MRI. Participants who have mid wall fibrosis (heart scarring) are randomised to receive either early surgical intervention (group A) or routine care (group B). Participants who have no mid wall fibrosis are randomised to routine care with study follow up (group C) or without study follow up (group D).

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

The result of the cardiac MRI will be blinded to care provider, participant and investigator. Group A will be unblinded, as participants can only enter group A if mid-wall fibrosis is present. Groups B and C will appear identical and the groups combined so the presence of mid-wall fibrosis will be blinded. Group D will be unblinded, as participants can only enter group D if mid-wall fibrosis is not present.

Outcome assessors will be blinded to allocation in all groups where outcome is adjudicated (groups A, B and C)

Study Groups

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Group A: Early intervention

Patients will be referred immediately for aortic valve intervention.

Group Type EXPERIMENTAL

Aortic valve intervention

Intervention Type PROCEDURE

The choice of either surgical aortic valve replacement or transcatheter aortic valve implantation (TAVI) will be made by the local clinical team according to local policies. In patients undergoing surgical replacement the choice of surgical technique and type of valve replacement used will be at the discretion of the operating surgeon. Patients found to have significant coronary artery disease requiring concomitant coronary artery bypass surgery will not be excluded. Similarly the choice of TAVI valve and need for percutaneous coronary intervention will be made by the TAVI heart team. The procedure should be performed as soon as possible and ideally within four months of randomisation and allocation to group A.

Group B: Routine care

Patients will be invited back for clinical follow up according to local policy. Decision making regarding future aortic valve intervention will be taken by the participant's clinical team (cardiologist and cardiac surgeon).

Group Type NO_INTERVENTION

No interventions assigned to this group

Group C: Routine care

Patients will be invited back for clinical follow up according to local policy. Decision making regarding future aortic valve intervention will be taken by the patient's clinical team (cardiologist and cardiac surgeon). Group C will appear identical to Group B

Group Type NO_INTERVENTION

No interventions assigned to this group

Group D: No further study follow up

Patients will be invited back for clinical follow up according to local policy. Decision making regarding future aortic valve intervention will be taken by the patient's clinical team (cardiologist and cardiac surgeon). No further study follow up will take place but personal data will be retained for future data linkage.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Aortic valve intervention

The choice of either surgical aortic valve replacement or transcatheter aortic valve implantation (TAVI) will be made by the local clinical team according to local policies. In patients undergoing surgical replacement the choice of surgical technique and type of valve replacement used will be at the discretion of the operating surgeon. Patients found to have significant coronary artery disease requiring concomitant coronary artery bypass surgery will not be excluded. Similarly the choice of TAVI valve and need for percutaneous coronary intervention will be made by the TAVI heart team. The procedure should be performed as soon as possible and ideally within four months of randomisation and allocation to group A.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

1. Severe aortic stenosis (aortic valve jet velocity ≥4.0 m/s, or aortic valve area indexed to body surface area \<0.6cm2/m2 with aortic jet velocity ≥3.5m/s)
2. Age over 18 years
3. No symptoms attributable to aortic stenosis that require aortic valve replacement

Exclusion Criteria

1. Deemed lower risk for mid-wall fibrosis on screening
2. Planned cardiac surgery
3. Previous valve replacement
4. Severe hypertension (systolic \>180 or diastolic \>110 mmHg)
5. Acute pulmonary oedema or cardiogenic shock
6. Left ventricular ejection fraction \<50% on cardiac MRI
7. Significant abnormalities on cardiac MRI that would prevent enrolment
8. Coexistent severe aortic regurgitation or mitral regurgitation
9. Coexistent mitral stenosis greater than mild in severity
10. Coexistent hypertrophic cardiomyopathy or cardiac amyloidosis
11. Any contraindication to MRI scanning (such as permanent pacemaker)
12. Advanced renal impairment (glomerular filtration rate \<30 mL/min/1.73 m2)
13. Pregnancy or breast feeding
14. Patient judged to be unfit to be considered for aortic valve replacement or transcatheter aortic valve implantation
15. Patient declines to consider undergoing valve replacement surgery or transcatheter aortic valve implantation
16. Inability to give informed consent
17. Previous randomisation into this study

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No