Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation

Study Overview
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Brief Summary
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Narrowing of coronary arteries interferes with blood flow and can cause chest pain. But patients may have more than one narrowing and studies have shown that not all narrowings need to be treated. To identify the narrowings that need treating cardiologists sometimes quantify the extent of the narrowing by measuring fractional flow reserve (FFR, the ratio of the pressure in the aorta to the pressure downstream of the narrowing).This technique requires the administration of drugs that add cost and time to the procedure and in some countries are simply unavailable. As a result despite the clear health and healthcare costs benefits of FFR its use is limited to less than 5% of procedure. We have developed a new technique called the instantaneous wave-free ratio (iFR) that does not require the administration of drugs for its accurate assessment. It has been approved for use in this indication. This study aims to compare clinical outcomes of patients whose treatment has been guided by iFR to those whose treatment has been guided by FFR. If iFR is found to provide the same clinical outcomes as FFR its adoption will permit the clear benefits of this approach of identifying the coronary narrowings that really need treatment to be applicable to a much larger patient population and further improve healthcare costs.

Detailed Description
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Design: Patients with one or more coronary stenoses, in which the physiological severity from coronary angiography is in question, will be randomised 1:1 to use of the instantaneous wave free ratio (iFR) or fractional flow reserve (FFR) to guide the treatment strategy for percutaneous coronary intervention (PCI). Aims: To assess whether the iFR is non-inferior to FFR when used to guide treatment of coronary stenosis with PCI. Outcome measures: The primary endpoint will be major adverse cardiac event rate in the iFR and FFR groups at 30 days, 1, 2, and 5 years. Population: This will be an international multi-centre study of 2500 patients. From population estimates, 35% of the total study population will present with stable angina and 65% will have acute coronary syndrome. Eligibility: Patients will be eligible when the physiological severity of a stenosis within a vessel is in question. In the cases of stable angina this will be confined to the target vessel, or with acute coronary syndrome assessment this will be made in the non-culprit vessel. Duration: Anticipated recruitment is 12 months. Follow-up will be performed at 30 days, 1, 2 and 5 years. Results: Primary outcome results will be reported in Spring 2017.

Official Title
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Prospective, Multi-center, Double Blind, Randomised Study to Test the Safety of Deferral of Stenting in Physiological Non-significant Lesions in a Clinical Population of Intermediate Stenoses Using iFR and FFR

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Device: iFR
* Device: FFR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years of age Willing to participate and able to understand, read and sign the informed consent document before the planned procedure Eligible for coronary angiography and/or percutaneous coronary intervention Coronary artery disease with at least 1 or more native major epicardial vessels or their branches by coronary angiogram with visually assessed de novo coronary stenosis in which the physiological severity of the lesion is in question (typically 40-70% diameter stenosis). Stable angina or acute coronary syndrome (non-culprit vessels only and outside of primary intervention during acute STEMI) Exclusion criteria: Previous Coronary Artery Bypass surgery with patent grafts to the interrogated vessel Significant left main stenosis (>50% narrowing) Tandem stenoses separated by more than 10 mm that require separate pressure guide wire interrogation or percutaneous coronary intervention (PCI) (not to be interrogated or treated as a single stenosis) Total coronary occlusions (CTOs). NOTE: Patients with CTOs can be included if i) treatment of the CTO is completed first, ii) the CTO PCI is successful, iii) the CTO PCI is successful and iii) the physiological lesion is in another vessel Restenotic lesions Hemodynamic instability at the time of intervention (heart rate<50 beats per minute, systolic blood pressure <90mmHg), balloon pump Significant contraindication to adenosine administration (e.g. heart block, severe asthma) Contraindications to PCI (percutaneous coronary intervention) or drug-eluting stent (DES) implantation Heavily calcified or tortuous vessels Significant hepatic or lung disease (chronic pulmonary obstructive disease), and/or malignant disease with unfavourable prognosis that may influence survival within the next 5 years Pregnancy STEMI (ST elevation myocardial infarction) within 48 hours of procedure Severe valvular heart disease ACS patients in whom more than one target vessel is present

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: iFR<br>Treatment guided by iFR | Device: iFR<br>* Treatment guided by instantaneous wave-free ratio<br>|
| Active Comparator: FFR<br>Treatment guided by FFR | Device: FFR<br>* Treatment guided by Fractional Flow Reserve<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Adverse Cardiac Events | Composite of death, myocardial infarction, unplanned revascularisation | 30 days, 1, 2 and 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death (all cause) |  | 30 days, 1, 2 and 5 years | 
| Death (cardiovascular) |  | 30 days, 1, 2 and 5 years | 
| Myocardial Infarction |  | 30 days, 1, 2 and 5 years | 
| Repeat revascularisation |  | 30 days, 1, 2 and 5 years | 
| Cost associated to iFR or FFR measurement | Cost associated to iFR or FFR | 30 days, 1, 2 and 5 years | 
| Quality of life assessed by EQ-5D-5L and Seattle Angina Questionnaire |  | 30 days, 1, 2 and 5 years | 
| Cost savings of removing secondary investigations | 7) Cost savings of removing secondary investigations, by assessing/treating non-culprit acute coronary syndrome (ACS) at the time of index presentation. | 30 days, 1, 2 and 5 years |