Aortic StenosisPRIMID-ASNCT01658345
Microvascular Dysfunction in Aortic Stenosis
An observational study of Aortic Stenosis, run by University Hospitals, Leicester at 3 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Aortic Stenosis
- How many people
- 175 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- Apr 2012to Oct 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Cardiology outpatients department and echocardiography department.
Who may be able to join
- Moderate-severe aortic stenosis (2 or more of: AVA < 1.5cm2, peak PG >36mmHg or mean PG > 25mmHg).
- Asymptomatic.
- Age > 18 years and < 85 years.
- Prepared to consider AVR if symptoms develop.
- Ability to perform bicycle exercise test
Who cannot join
- History of CABG or MI within previous 6 months.
- Severe valvular disease other than AS.
- Previous Valve surgery
- Persistent Atrial Fibrillation or Flutter
- History of Heart Failure
- Severe Asthma.
Show all 14Show fewer
- Severe renal impairment eGFR < 30ml/min.
- Planned aortic valve replacement.
- Significant LV systolic dysfunction (EF < 40%)
- Any absolute contraindication to CMR
- Any absolute contraindication to Adenosine
- Participation in an Interventional Clinical Trial at Inclusion.
- Other medical condition that limits life expectancy or precludes AVR.
- Pregnancy
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
University of Glasgow
Glasgow, G12 8QQ
Leeds General Infirmary
Leeds, West Yorkshire, LS1 3EX
Glenfield Hospital
Leicester, Leicestershire, LE3 9QP
About this study
Official title: 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.
Read the 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.
- Conditions
- Aortic Stenosis
- Keywords
- aortic stenosis, asymptomatic, microvascular dysfunction, Cardiac MRI
- Medical subject headings
- Aortic Valve Stenosis
What is being measured
The primary outcome is the main question the study is designed to answer.
Typical AS Symptoms necessitating AVR.
Measured: 12 months
Cardiovascular death.
Measured: 12 months
Major adverse cardiovascular events (MACE)
MACE: hospitalisation with heart failure, chest pain, syncope, arrhythmia or stroke
Measured: 12 months
Secondary outcomes (2)
Individual components of primary composite outcome measures.
Typical symptoms requiring referral for AVR, cardiovascular death, Major adverse cardiovascular events.
Measured: Upto 2 years.
Development of typical symptoms, AVR, death from any cause or MACE during the entire study period.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2012 (estimated)
- Study startApr 2012
- Primary completionNov 2013
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Aortic StenosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 175 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospitals, Leicester
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gerry P McCann, MBChB, MD, Principal investigator, University of Leicester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01658345
- Sponsor's protocol ID
- 87768
- Acronym
- PRIMID-AS
- Status last verified
- Feb 2015
- First submitted
- 6 Jul 2012
- Last updated
- 23 Feb 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Steadman CD, Jerosch-Herold M, Grundy B, Rafelt S, Ng LL, Squire IB, Samani NJ, McCann GP. Determinants and functional significance of myocardial perfusion reserve in severe aortic stenosis. JACC Cardiovasc Imaging. 2012 Feb;5(2):182-9. doi: 10.1016/j.jcmg.2011.09.022.
PubMed 22340825McCann GP, Steadman CD, Ray SG, Newby DE; British Heart Valve Society. Managing the asymptomatic patient with severe aortic stenosis: randomised controlled trials of early surgery are overdue. Heart. 2011 Jul;97(14):1119-21. doi: 10.1136/hrt.2011.223800. Epub 2011 Mar 12. No abstract available.
PubMed 21398695Steadman CD, Ray S, Ng LL, McCann GP. Natriuretic peptides in common valvular heart disease. J Am Coll Cardiol. 2010 May 11;55(19):2034-48. doi: 10.1016/j.jacc.2010.02.021.
PubMed 20447526Das P, Rimington H, Chambers J. Exercise testing to stratify risk in aortic stenosis. Eur Heart J. 2005 Jul;26(13):1309-13. doi: 10.1093/eurheartj/ehi250. Epub 2005 Apr 8.
PubMed 15820999Chan DCS, Singh A, Greenwood JP, Dawson DK, Lang CC, Berry C, Pakkal M, Everett RJ, Dweck MR, Ng LL, McCann GP. Effect of the 2017 European Guidelines on Reclassification of Severe Aortic Stenosis and Its Influence on Management Decisions for Initially Asymptomatic Aortic Stenosis. Circ Cardiovasc Imaging. 2020 Dec;13(12):e011763. doi: 10.1161/CIRCIMAGING.120.011763. Epub 2020 Dec 8.
PubMed 33287584Graham-Brown MP, Singh AS, Gulsin GS, Levelt E, Arnold JA, Stensel DJ, Burton JO, McCann GP. Defining myocardial fibrosis in haemodialysis patients with non-contrast cardiac magnetic resonance. BMC Cardiovasc Disord. 2018 Jul 13;18(1):145. doi: 10.1186/s12872-018-0885-2.
PubMed 30005636Singh A, Greenwood JP, Berry C, Dawson DK, Hogrefe K, Kelly DJ, Dhakshinamurthy V, Lang CC, Khoo JP, Sprigings D, Steeds RP, Jerosch-Herold M, Neubauer S, Prendergast B, Williams B, Zhang R, Hudson I, Squire IB, Ford I, Samani NJ, McCann GP. Comparison of exercise testing and CMR measured myocardial perfusion reserve for predicting outcome in asymptomatic aortic stenosis: the PRognostic Importance of MIcrovascular Dysfunction in Aortic Stenosis (PRIMID AS) Study. Eur Heart J. 2017 Apr 21;38(16):1222-1229. doi: 10.1093/eurheartj/ehx001.
PubMed 28204448Singh A, Ford I, Greenwood JP, Khan JN, Uddin A, Berry C, Neubauer S, Prendergast B, Jerosch-Herold M, Williams B, Samani NJ, McCann GP. Rationale and design of the PRognostic Importance of MIcrovascular Dysfunction in asymptomatic patients with Aortic Stenosis (PRIMID-AS): a multicentre observational study with blinded investigations. BMJ Open. 2013 Dec 18;3(12):e004348. doi: 10.1136/bmjopen-2013-004348.
PubMed 24353258
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prognostic Importance of Microvascular Dysfunction in Asymptomatic Patients With Aortic Stenosis (PRIMID-AS)
- ClinicalTrials.gov ID
- NCT01658345
- Acronym / sponsor ID
- PRIMID-AS / 87768
- Conditions
- Aortic Stenosis
- Keywords
- aortic stenosis, asymptomatic, microvascular dysfunction, Cardiac MRI
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 175 participants (actual)
- Lead sponsor
- University Hospitals, LeicesterUniversity, hospital or other
- Study start
- Apr 2012
- Primary completion
- Nov 2013 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 7 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Cardiology outpatients department and echocardiography department.
Key inclusion criteria (5 listed)
- Moderate-severe aortic stenosis (2 or more of: AVA < 1.5cm2, peak PG >36mmHg or mean PG > 25mmHg).
- Asymptomatic.
- Age > 18 years and < 85 years.
- Prepared to consider AVR if symptoms develop.
- Ability to perform bicycle exercise test
Key exclusion criteria (14 listed)
- History of CABG or MI within previous 6 months.
- Severe valvular disease other than AS.
- Previous Valve surgery
- Persistent Atrial Fibrillation or Flutter
- History of Heart Failure
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
2 secondary outcomes
Individual components of primary composite outcome measures.
Time frame: Upto 2 years.
Development of typical symptoms, AVR, death from any cause or MACE during the entire study period.
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2015.
- Background: PubMed 22340825Steadman CD, Jerosch-Herold M, Grundy B, Rafelt S, Ng LL, Squire IB, Samani NJ, McCann GP. Determinants and functional significance of myocardial perfusion reserve in severe aortic stenosis. JACC Cardiovasc Imaging. 2012 Feb;5(2):182-9. doi: 10.1016/j.jcmg.2011.09.022.
- Background: PubMed 21398695McCann GP, Steadman CD, Ray SG, Newby DE; British Heart Valve Society. Managing the asymptomatic patient with severe aortic stenosis: randomised controlled trials of early surgery are overdue. Heart. 2011 Jul;97(14):1119-21. doi: 10.1136/hrt.2011.223800. Epub 2011 Mar 12. No abstract available.
- Background: PubMed 20447526Steadman CD, Ray S, Ng LL, McCann GP. Natriuretic peptides in common valvular heart disease. J Am Coll Cardiol. 2010 May 11;55(19):2034-48. doi: 10.1016/j.jacc.2010.02.021.
- Background: PubMed 15820999Das P, Rimington H, Chambers J. Exercise testing to stratify risk in aortic stenosis. Eur Heart J. 2005 Jul;26(13):1309-13. doi: 10.1093/eurheartj/ehi250. Epub 2005 Apr 8.
- Derived from this study: PubMed 33287584Chan DCS, Singh A, Greenwood JP, Dawson DK, Lang CC, Berry C, Pakkal M, Everett RJ, Dweck MR, Ng LL, McCann GP. Effect of the 2017 European Guidelines on Reclassification of Severe Aortic Stenosis and Its Influence on Management Decisions for Initially Asymptomatic Aortic Stenosis. Circ Cardiovasc Imaging. 2020 Dec;13(12):e011763. doi: 10.1161/CIRCIMAGING.120.011763. Epub 2020 Dec 8.
- Derived from this study: PubMed 30005636Graham-Brown MP, Singh AS, Gulsin GS, Levelt E, Arnold JA, Stensel DJ, Burton JO, McCann GP. Defining myocardial fibrosis in haemodialysis patients with non-contrast cardiac magnetic resonance. BMC Cardiovasc Disord. 2018 Jul 13;18(1):145. doi: 10.1186/s12872-018-0885-2.
- Derived from this study: PubMed 28204448Singh A, Greenwood JP, Berry C, Dawson DK, Hogrefe K, Kelly DJ, Dhakshinamurthy V, Lang CC, Khoo JP, Sprigings D, Steeds RP, Jerosch-Herold M, Neubauer S, Prendergast B, Williams B, Zhang R, Hudson I, Squire IB, Ford I, Samani NJ, McCann GP. Comparison of exercise testing and CMR measured myocardial perfusion reserve for predicting outcome in asymptomatic aortic stenosis: the PRognostic Importance of MIcrovascular Dysfunction in Aortic Stenosis (PRIMID AS) Study. Eur Heart J. 2017 Apr 21;38(16):1222-1229. doi: 10.1093/eurheartj/ehx001.
- Derived from this study: PubMed 24353258Singh A, Ford I, Greenwood JP, Khan JN, Uddin A, Berry C, Neubauer S, Prendergast B, Jerosch-Herold M, Williams B, Samani NJ, McCann GP. Rationale and design of the PRognostic Importance of MIcrovascular Dysfunction in asymptomatic patients with Aortic Stenosis (PRIMID-AS): a multicentre observational study with blinded investigations. BMJ Open. 2013 Dec 18;3(12):e004348. doi: 10.1136/bmjopen-2013-004348.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gerry P McCann, MBChB, MD principal investigator
University of Leicester
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Aortic Stenosis, run by University Hospitals, Leicester at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Typical AS Symptoms necessitating AVR. (time frame: 12 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01658345, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2015.