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Microvascular Dysfunction in Aortic Stenosis (PRIMID-AS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01658345
Recruitment Status : Completed
First Posted : August 7, 2012
Last Update Posted : February 23, 2015
Sponsor:
Information provided by (Responsible Party):
University Hospitals, Leicester

Tracking Information
First Submitted Date July 6, 2012
First Posted Date August 7, 2012
Last Update Posted Date February 23, 2015
Study Start Date April 2012
Actual Primary Completion Date November 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: August 6, 2012)
  • Typical AS Symptoms necessitating AVR. [ Time Frame: 12 months ]
  • Cardiovascular death. [ Time Frame: 12 months ]
  • Major adverse cardiovascular events (MACE) [ Time Frame: 12 months ]
    MACE: hospitalisation with heart failure, chest pain, syncope, arrhythmia or stroke
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: August 6, 2012)
  • Individual components of primary composite outcome measures. [ Time Frame: Upto 2 years. ]
    Typical symptoms requiring referral for AVR, cardiovascular death, Major adverse cardiovascular events.
  • Development of typical symptoms, AVR, death from any cause or MACE during the entire study period. [ Time Frame: 2 years ]
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Microvascular Dysfunction in Aortic Stenosis
Official Title Prognostic Importance of Microvascular Dysfunction in Asymptomatic Patients With Aortic Stenosis (PRIMID-AS)
Brief Summary

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.

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
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:

With consent, a blood sample (up to 50ml) will be drawn and banked for prospective research studies. All research projects will be related to cardiovascular disease and approved by the Trial Steering Committee (TSC) or a committee delegated this responsibility by the TSC.

All tissue will be collected, stored and disposed of in accordance with the Codes of Practice as laid out by the Human Tissue Authority.

Sampling Method Non-Probability Sample
Study Population Cardiology outpatients department and echocardiography department.
Condition Aortic Stenosis
Intervention Not Provided
Study Groups/Cohorts Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: February 20, 2015)
175
Original Estimated Enrollment
 (submitted: August 6, 2012)
170
Actual Study Completion Date October 2014
Actual Primary Completion Date November 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria

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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number NCT01658345
Other Study ID Numbers 87768
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party University Hospitals, Leicester
Study Sponsor University Hospitals, Leicester
Collaborators Not Provided
Investigators
Principal Investigator: Gerry P McCann, MBChB, MD University of Leicester
PRS Account University Hospitals, Leicester
Verification Date February 2015