Physiologic Assessment of Coronary Stenosis Following PCI

Study Overview
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Brief Summary
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This is a pilot study designed to assess the relationship between iFR (instantaneous wave-free ratio) pullback and the distribution of coronary atheroma/stenoses as assessed by Quantitative Coronary Angiography (QCA) post angiographically successful PCI (Percutaneous Coronary Intervention).

Detailed Description
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DEFINE-PCI is a multi-center, prospective, non-significant risk study in up to 25 centers in USA and internationally. Consented subjects with CAD (Coronary Artery Disease) who undergo physiologic lesion assessment with iFR<0.90 in at least 1 coronary artery are eligible for participation. After successful PCI to all culprit lesions based on angiographic assessment of the treating physician, a blinded post-PCI iFR and iFR pullback will be performed. The proportion of patients with impaired post-PCI iFR will be assessed, and the number of patients in whom ischemia could theoretically be normalized with further PCI determined. Additionally, the association between the post-PCI iFR results and cardiovascular events and clinical symptoms will be assessed. Follow-up will be at 1, 6 and 12 months, including administration of quality of life questionnaires.

Official Title
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DEFINE PCI: Physiologic Assessment of Coronary Stenosis Following PCI

Conditions
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Coronary Stenosis, Coronary Artery Disease, Angina, Unstable, Angina, Stable

Intervention / Treatment
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* Diagnostic Test: iFR pullback


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be > 18 years old Subjects presenting with stable angina, silent ischemia or non-ST-elevation ACS (acute coronary syndrome) (unstable angina or biomarker positive) Single vessel CAD with at least 2 separate lesions (≥10 mm apart) of ≥40% stenosis or a single long lesion of ≥20mm OR multi-vessel CAD, defined as at least 2 vessels with ≥40% stenosis Pre-PCI iFR performed in all vessels intended for PCI Pre-PCI iFR of <0.90 of at least 1 stenosis Subjects are able and willing to comply with scheduled visits and tests and to provide informed consent. Exclusion Criteria: Pregnant or planning to become pregnant for the duration of the study Acute STEMI (ST-elevated Myocardial Infarction) within the past 7 days Cardiogenic shock (sustained (>10 min) systolic blood pressure < 90 mmHg in absence of inotropic support or the presence of an intra-aortic balloon pump). Ionotropic or temporary pacing requirement Sustained ventricular arrhythmias Prior CABG (Coronary Artery Bypass Graft) Known ejection fraction ≤30% Chronic Total Occlusion (CTO) Known severe mitral or aortic stenosis. Any known medical comorbidity resulting in life expectancy < 12 months. Participation in any investigational study that has not yet reached its primary endpoint. Known severe renal insufficiency (eGFR <30 ml/min/1.72 m2). TIMI flow <3 at baseline Intra-coronary thrombus on baseline angiography

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| iFR post angiographically successful PCI<br> | Diagnostic Test: iFR pullback<br>* iFR pullback assessment post angiographically successful PCI<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Residual Ischemia (iFR <0.90) | Residual ischemia is defined as iFR measurement <0.90 after operator-assessed angiographically successful PCI (residual diameter stenosis <50% in any treated lesion in the target vessel) This outcome describes the number of participants that had a residual ischemia (defined as iFR<0.90) after a PCI that appeared to be successful based on angiography. | end of procedure/intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac Events | Composite endpoint of cardiac death, target vessel myocardial infarction, ischemia-driven target vessel revascularization or recurrent ischemia at one year after PCI | 12 months | 
| Target Vessel Failure | Target vessel failure defined as cardiac death, target vessel myocardial infarction, ischemia-driven target vessel revascularization | 12 months | 
| Quality of Life Change From Baseline to 12 Months Follow-up | Quality of life (assessed by the Seattle Angina Questionnaire) at baseline, 30-days, 6 months and 1 year (12 months). Minimum score is 0 and maximum score is 100, with a high score representing a more positive quality of life score. Outcome is the change in score from baseline to 12 months follow-up. | 12 months | 
| Cardiac Mortality | All-cause and cardiac mortality at one year | 12 months | 
| Target Vessel MI | Target vessel Myocardial infarction at one year | 12 month | 
| Target Vessel Revascularization | Ischemia-driven target vessel revascularization at one year | 12 month | 
| Recurrent Ischemia | Recurrent ischemia at one-year | 12 month | 
| Correlation Between iFR and Angiographic Visual Interpretation | Correlation between iFR <0.90 and coronary stenosis >50% assessed by visual interpretation. This was tested using generalized estimating equations for logistic regression to account for the correlation of observations from the same subject. An absolute value of exactly 1 implies that a linear equation describes the relationship between iFR and visual interpretation of the angiography. Outcome reports how well the iFR value and the visual interpretation are in agreement (for example, when iFR <0.90 and coronary stenosis >50% assessed by visual interpretation the correlation is 1). | at the end of the procedure/intervention | 
| Number of Participants in Which the iFR Would Become Non-significant if a Focal Stenosis Demonstrated by iFR Pullback Were Treated With PCI | Number of participants in which the iFR would become non-significant if a focal stenosis demonstrated by iFR pullback were treated with PCI | Procedural | 
| Differentiation | Differentiation of the cause for impaired iFR | End of procedure /intervention | 
| Delta iFR | Predictors of delta iFR before and after PCI, or predictors of impaired iFR Outcome is presented as the odds ratio (OR) that the post-PCI iFR will be <0.90. An OR > 1 means greater odds that the post-PCI iFR is <0.90, OR = 1 means there is no association, and OR < 1 means there is a lower odds that the post-PCI iFR is <0.90. | at the end of the procedure/intervention |