Microvascular Dysfunction in Aortic Stenosis (PRIMID-AS)

February 20, 2015 updated by: University Hospitals, Leicester

Prognostic Importance of Microvascular Dysfunction in Asymptomatic Patients With Aortic Stenosis (PRIMID-AS)

Aortic stenosis (AS), or narrowing of the aortic valve, is the commonest condition requiring valve surgery in the developed world. It is currently not known what determines who will go on to develop symptoms. Exercise testing may be able to identify these patients better than the severity of the narrowing itself, but with some limitations.

The purpose of this study is to compare whether MRI scanning or exercise testing can better identify patients with AS who are likely to benefit from surgery.

Design: The investigators will measure blood flow to the heart muscle with MRI scanning and perform exercise testing in 170 patients with AS and follow them for up to up to 2 years. Expected outcomes: MRI scanning will more accurately identify those patients with AS who will need surgery during this period. Anticipated Health Benefits: improved selection of patients with AS who are likely to benefit from early surgery. This is likely to reduce deaths in such patients.

Study Overview

Status

Completed

Conditions

Detailed Description

Surgical AVR remains the universally accepted management for symptomatic aortic stenosis (AS). However, the best management of severe aortic stenosis, in the absence of symptoms, remains one of the most controversial areas in modern Cardiology.

Exercise testing can identify asymptomatic patients with AS at increased risk, but with limited specificity. In a BHF funded project, the investigators have identified that cardiac MRI measured Myocardial Perfusion Reserve (MPR) may be a novel imaging biomarker in AS. MPR was the only independent predictor of aerobic exercise capacity (peak VO2) in patients with severe AS and was also inversely related to symptomatic status.

In this multi-centre, observational, cohort outcome study, the investigators will follow 175 patients with asymptomatic moderate to severe AS for a minimum of 12 months, and determine whether MPR is a better predictor of outcome than exercise testing, elucidate the mechanisms contributing to symptom development in AS and establish the determinants of MPR in AS. Patients will be recruited from tertiary Cardiac centres, as well as regional hospitals. Comprehensive CMR with adenosine stress to determine LV mass and function, focal and diffuse fibrosis and MPR; cardiopulmonary exercise testing (peak VO2 and exercise symptoms); rest and exercise echocardiography (AS severity, valve compliance) and NT-proBNP will be performed. The study will be run in conjunction with the Glasgow CTU. Investigations will be analysed blind to patient status and data will be entered in a validated database. Statistical analysis will be performed under the supervision of Prof. Ian Ford. The relationship between MPR and exercise testing with 1-year outcome will be analysed using logistic regression. Paired comparisons of the specificities of the two approaches on the same dataset will be carried out using McNemar's test.

The primary hypothesis is that MPR will be a better predictor of adverse outcome than exercise testing.

Study Type

Observational

Enrollment (Actual)

175

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Glasgow, United Kingdom, G12 8QQ
        • University of Glasgow
    • Leicestershire
      • Leicester, Leicestershire, United Kingdom, LE3 9QP
        • Glenfield Hospital
    • West Yorkshire
      • Leeds, West Yorkshire, United Kingdom, LS1 3EX
        • Leeds General Infirmary

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Cardiology outpatients department and echocardiography department.

Description

Inclusion Criteria:

  1. Moderate-severe aortic stenosis (2 or more of: AVA < 1.5cm2, peak PG >36mmHg or mean PG > 25mmHg).
  2. Asymptomatic.
  3. Age > 18 years and < 85 years.
  4. Prepared to consider AVR if symptoms develop.
  5. Ability to perform bicycle exercise test

Exclusion Criteria:

  1. History of CABG or MI within previous 6 months.
  2. Severe valvular disease other than AS.
  3. Previous Valve surgery
  4. Persistent Atrial Fibrillation or Flutter
  5. History of Heart Failure
  6. Severe Asthma.
  7. Severe renal impairment eGFR < 30ml/min.
  8. Planned aortic valve replacement.
  9. Significant LV systolic dysfunction (EF < 40%)
  10. Any absolute contraindication to CMR
  11. Any absolute contraindication to Adenosine
  12. Participation in an Interventional Clinical Trial at Inclusion.
  13. Other medical condition that limits life expectancy or precludes AVR.
  14. Pregnancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Major adverse cardiovascular events (MACE)
Time Frame: 12 months
MACE: hospitalisation with heart failure, chest pain, syncope, arrhythmia or stroke
12 months
Typical AS Symptoms necessitating AVR.
Time Frame: 12 months
12 months
Cardiovascular death.
Time Frame: 12 months
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Individual components of primary composite outcome measures.
Time Frame: Upto 2 years.
Typical symptoms requiring referral for AVR, cardiovascular death, Major adverse cardiovascular events.
Upto 2 years.
Development of typical symptoms, AVR, death from any cause or MACE during the entire study period.
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospitals, Leicester

Investigators

  • Principal Investigator: Gerry P McCann, MBChB, MD, University of Leicester

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2012

Primary Completion (Actual)

November 1, 2013

Study Completion (Actual)

October 1, 2014

Study Registration Dates

First Submitted

July 6, 2012

First Submitted That Met QC Criteria

August 6, 2012

First Posted (Estimate)

August 7, 2012

Study Record Updates

Last Update Posted (Estimate)

February 23, 2015

Last Update Submitted That Met QC Criteria

February 20, 2015

Last Verified

February 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 87768

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.

Clinical Trials on Aortic Stenosis

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Trinidad & Tobago

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe