- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05178368
MRI in Randomised Cohorts of Asymptomatic AS
Impact of Early Valve Replacement on Myocardial Scar in Asymptomatic Aortic Stenosis: an Observational MRI Study of Randomised Cohorts
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Ongoing randomised control trials (RCT) are testing the strategy of early AVR in asymptomatic severe AS ('The Early surgery in severe ASYmptomatic Aortic Stenosis': EASY-AS and 'Early Valve Replacement guided by Biomarkers of Left Ventricular Decompensation in Asymptomatic Patients with Severe Aortic Stenosis': EVOLVED), and if positive, have the potential to shift the timing of intervention to earlier disease. With TAVR recently being shown to be non-inferior to SAVR in low risk, mostly symptomatic patients, this also has the potential to be extended to asymptomatic patients.
MRI studies have shown that up to 50% of those with asymptomatic AS already have scarring (LGE), which is only partially reversible even after AVE, and remains a marker of mortality. It is not known if earlier valve replacement will lead to less scar burden within the myocardium.
Patient reported outcome measures (PROM) are increasingly recognised as an important outcome measure of surgery, especially in an elderly population, for whom a significant increase in survival may be neither possible, nor sought by the patient. World Health Organisation Disability Assessment Schedule-2 (WHODAS-2) is a standardised cross-cultural measurement of health status assessing functioning and disability in major life domains, that has been shown to be a valid and reliable instrument for assessment of disability. A comprehensive formal review of PROMS instruments in patients receiving medical treatment for heart failure concluded that the Euroqol (EQ5D) and Minnesota Living with Heart Failure Questionnaire (MLHFQ) were the most appropriate to measure quality of life in this group. Euroqol is the most commonly used generic instrument in Europe, and showed improvement at 1 year post-AVR for severe AS. MLHFQ is a cardiovascular disease-specific tool that has been shown to be reliable, valid and responsive to therapeutic intervention in patients undergoing valve surgery. Understanding the effect of intervention on PROMs can aid shared decision-making and help shape future individualised recommendations.
This prospective, observational mechanistic study will maximise the opportunity offered by ongoing RCTs, to try and establish the effect of the two treatment strategies (early vs late AVR) on cardiac reverse remodelling (in particular fibrosis burden), PROMs and peri-operative recovery.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Anvesha Singh, Dr
- Phone Number: +44 116 252 3183
- Email: as707@leicester.ac.uk
Study Locations
-
-
Leicestershire
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Leicester, Leicestershire, United Kingdom, LE3 9QP
- Recruiting
- Glenfield Hospital
-
Contact:
- Dr Anvesha Singh, MBBS, PhD
- Phone Number: Tel: +44(0)116 252 3183
- Email: as707@leicester.ac.uk
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- Willing to and able to consent
- Participant in an RCT randomising patients with asymptomatic severe AS to early AVR vs standard care
- Severe aortic stenosis, as defined by original trial's inclusion criteria
- Asymptomatic at the time of randomisation in the RCT
- Willingness to have 1-2 cardiac MRI scan(s)
Exclusion Criteria:
- Contra-indication to MRI.
- eGFR <30.
- Severe claustrophobia (precluding MRI).
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Early aortic valve replacement
Asymptomatic severe aortic stenosis patients randomised to early aortic valve replacement
|
The choice of intervention will be made by the local clinical team.
The timing of intervention will be determined by randomisation as part of the main EASY/EVOLVED trials
|
Standard care
Asymptomatic severe aortic stenosis patients randomised to 'watchful waiting' until symptom onset.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Total amount of fibrosis (measured by LGE on MRI) in those randomised to early AVR vs standard care.
Time Frame: 3 years
|
Measured by percentage of late gadolinium enhancement on MRI, between those randomised to early AVR vs standard care.
|
3 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Differences in patient reported outcome measures (health related quality of life) between the two groups
Time Frame: 3 years
|
Measured using the questionnaire EuroQol- 5 (EQ-5D-5L) EuroQol- 5 Dimension is a standardised measure of health-related quality of life and consists of 2 pages. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. |
3 years
|
Differences in patient reported outcome measures (patient perceptions of living with heart failure) between the two groups
Time Frame: 3 years
|
Measured using the Minnesota Living with Heart Failure questionnaire (MLHF) Minnesota Living with Heart Failure questionnaire aids to systematically and comprehensively assess the patient's perceptions of the effects of heart failure and its treatment on his or her daily life. It is a 21-item paper self- administered questionnaire designed as a measure of heart failure, as indicated by its adverse effects on patients' lives. The MLHFQ quantifies a single overall score as a measure of the impact of heart failure on the patient's life. |
3 years
|
Differences in patient reported outcome measures (in assessing functioning and disability in major life domains) between the two groups
Time Frame: 3 years
|
Measured using the World Health Organisation Disability Assessment Schedule-2 (WHODAS-2) questionnaire World Health Organisation Disability Assessment Schedule-2 (WHODAS-2) is a standardised cross-cultural measurement of health status assessing functioning and disability in major life domains, that has been shown to be a valid and reliable instrument for assessment of disability. It is a 36-item measure that assesses disability in adults age 18 years and older. |
3 years
|
Difference in peri-operative recovery between the two groups.
Time Frame: 30 days from date of surgery
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Days at home within 30 days of surgery
|
30 days from date of surgery
|
Differences in reverse remodelling (by left ventricular volume) between the two groups.
Time Frame: 3 years
|
LV end-diastolic volume index in ml/m2
|
3 years
|
Differences in reverse remodelling (by left ventricular mass) between the two groups.
Time Frame: 3 years
|
LV mass index in g/m2
|
3 years
|
Differences in reverse remodelling (by left ventricular mass/volume) between the two groups.
Time Frame: 3 years
|
LV mass/volume ratio
|
3 years
|
Differences in reverse remodelling (by left ventricular ejection fraction) between the two groups.
Time Frame: 3 years
|
LV ejection fraction in %
|
3 years
|
Differences in reverse remodelling (by myocardial perfusion reserve) between the two groups.
Time Frame: 3 years
|
Myocardial perfusion reserve (in those having optional stress perfusion)
|
3 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Anvesha Singh, Dr, University of Leicester
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 0824
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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