Combined Pressure and Flow Measurements to Guide Treatment of Coronary Stenoses

Study Overview
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Brief Summary
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This study evaluates the prognostic value and therapeutic potential of combined pressure and flow measurements when evaluating a coronary artery stenosis. Lesions with intact coronary flow reserve (CFR) despite a reduced fractional flow reserve (FFR) will receive optimal medical therapy. Only lesions with a simultaneous reduction in both CFR and FFR will be treated with percutaneous coronary intervention (PCI).

Detailed Description
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Pressure and flow represent the two physiologic variables that can be measured directly inside a coronary artery. Already pressure measurements have proven their clinical value in the form of fractional flow reserve (FFR). However, myocardial function can remain intact with sufficient flow, even at a low perfusion pressure. Therefore, combined pressure and flow measurements provide a more complete description of physiologic stenosis severity as a guide to medical treatment versus revascularization. Based on existing work relating the most common flow measurement, coronary flow reserve (CFR), to FFR and linking both variables with subsequent prognosis, we hypothesize that lesions with an intact CFR>=2.0 can be reasonably treated with medical therapy despite a reduced FFR<=0.8.

Official Title
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DEFINE-FLOW (Distal Evaluation of Functional Performance With Intravascular Sensors to Assess the Narrowing Effect - Combined Pressure and Doppler FLOW Velocity Measurements)

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Other: Percutaneous coronary intervention (PCI)
* Other: Optimal medical therapy (OMT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years. Eligible for PCI based on local practice standards during the current procedure (PCI cannot be staged). At least one epicardial stenosis of ≥50% diameter (by visual or quantitative assessment) and meeting the following criteria as determined by the operator based on either a prior or the current diagnostic angiogram: <100% diameter (not a chronic, total occlusion); in a native coronary artery (including side branches but excludes bypass grafts); of ≥2.5mm reference diameter (near the level of the stenosis); and supplies sufficiently viable myocardium (exclude regions of known, prior, transmural myocardial infarction). Ability to understand and the willingness to sign a written informed consent. Exclusion Criteria: Anatomic exclusions: Prior CABG. Preferred treatment strategy for revascularization would be CABG based on local practice standards. Left main coronary artery disease requiring revascularization. Extremely tortuous or calcified coronary arteries precluding intracoronary physiologic measurements. Operators may also exclude subtotal or similar high-grade lesions, which in their judgment may be threatened by ComboWire placement. Known severe LV hypertrophy (septal wall thickness at echocardiography of >13 mm). Clinical exclusions: Inability to receive intravenous adenosine (for example, severe reactive airway disease, marked hypotension, or high-grade AV block without pacemaker). Recent (within 3 weeks prior to cardiac catheterization) ST-segment elevation myocardial infarction (STEMI) in any arterial distribution (not specifically target lesion). Culprit lesions (based on clinical judgment of the operator) for either STEMI or non-STEMI cannot be included. Severe cardiomyopathy (LV ejection fraction <30%). Planned need for cardiac surgery (for example, valve surgery, treatment of aortic aneurysm, or septal myomectomy). General exclusions: A life expectancy of less than 2 years. Inability to sign an informed consent, due to any mental condition that renders the subject unable to understand the nature, scope, and possible consequences of the trial or due to mental retardation or language barrier. Potential for non-compliance towards the requirements for follow-up visits. Participation or planned participation in another cardiovascular clinical trial before completing the 24 month follow-up.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: All patients<br>All lesions undergo simultaneous assessment with a combined pressure and flow sensor | Other: Percutaneous coronary intervention (PCI)<br>* For lesions with both FFR<=0.8 and CFR<2.0<br>Other: Optimal medical therapy (OMT)<br>* For lesions with FFR>0.8 or CFR>=2.0 or both<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major adverse cardiac events | All-cause death, non-fatal myocardial infarction, urgent and elective revascularization | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Angina (Canadian Cardiovascular Society (CCS) anginal class (or freedom from angina) | Canadian Cardiovascular Society (CCS) anginal class (or freedom from angina) | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fractional Flow Reserve, Myocardial, Coronary Flow Reserve