Fractional FLow Reserve And IVUS for Clinical OUtcomes in Patients With InteRmediate Stenosis

Study Overview
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Brief Summary
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To compare the safety and efficacy of FFR (fractional flow reserve)-guided percutaneous coronary intervention (PCI) strategy with IVUS (intravascular ultrasound [IVUS])-guided PCI in patients with intermediate coronary stenosis.

Detailed Description
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Study overview This study is a prospective, open-label, randomized, multicenter trial to test the safety and efficacy of physiology- or imaging-guided PCI in patients with intermediate coronary stenosis. The primary hypothesis is that FFR-guided strategy will show non-inferior rate of patients-oriented composite outcomes (POCO) at 24 months after randomization, compared with IVUS-guided strategy in patients with intermediate coronary stenosis. Study population and sample size calculation Sample Size Calculation Based on the event rates of previous trials, investigators predicted the rates of POCO at 24 months after PCI will be 10% in the FFR-guided arm, and 12% in the IVUS-guided arm. Primary endpoint: patient-oriented composite outcome (a composite of all-cause death, MI, any repeat revascularization) at 24 months after PCI Design: non-inferiority , delta = 2.5% Sampling ratio: FFR-guided strategy : IVUS-guided strategy = 1:1 Type I error (α): One-sided 5% Accrual time : 2 years Total time : 4 years (accrual 2 year + follow-up 2 years) Assumption: POCO 10.0% vs. 12.0% in FFR or IVUS-guided strategy, respectively Statistical power (1- β): 90% Primary statistical method : Kaplan-Meier survival analysis with log-rank test Potential withdrawal rates : total 2% Stratification in Randomization: Presence of Diabetes Mellitus (600 patients (35%) will be Diabetic patients, with 300 patients in each group) Based on the above assumption, 1,700 patients (850 patients in each group) will be enrolled in this study with consideration of withdrawal rates. Research Materials and Indication for Revascularization For the FFR-guided strategy arm, a pressure-sensor wire system will be used and the criterion for revascularization is FFR ≤ 0.80. Hyperemia will be induced by intravenous infusion of adenosine (140ug/kg/min). For the IVUS-guided strategy arm, the criterion for revascularization is MLA ≤ 3mm2 or [3mm2 < MLA ≤ 4mm2 and plaque burden > 70%]. Funding This is an investigator-initiated study with grant support from Boston Scientific. Other than financial sponsorship, the company has no role in protocol development or the implementation, management, data collection, and analysis of this study.

Official Title
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Comparison of Clinical Outcomes Between Imaging and Physiology-guided Intervention Strategy in Patients With Intermediate Stenosis: Fractional FLow Reserve And IVUS for Clinical OUtcomes in Patients With InteRmediate Stenosis (FLAVOUR)

Conditions
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Stable Angina

Intervention / Treatment
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* Procedure: FFR-guided stenting
* Procedure: IVUS-guided stenting


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Subject must be ≥ 19 years ② Subject is able to verbally confirm understandings of risks, benefits and treatment alternatives of receiving invasive physiologic or imaging evaluation and PCI and he/she or his/her legally authorized representative provides written informed consent prior to any study related procedure. Patients suspected with ischemic heart disease ④ Patients with intermediate degree of stenosis (40-70% stenosis by visual estimation) eligible for stent implantation who need FFR or IVUS for further evaluation ⑤ Target vessel size > 2.5mm Target lesions located at the proximal to mid part of coronary artery Exclusion Criteria Known hypersensitivity or contraindication to any of the following medications: Heparin, Aspirin, Clopidogrel, Prasugrel, Ticagrelor, Adenosine. Active pathologic bleeding Gastrointestinal or genitourinary major bleeding within the prior 3 months. History of bleeding diathesis, known coagulopathy (including heparin-induced thrombocytopenia) ⑤ Non-cardiac co-morbid conditions with life expectancy < 2 years ⑥ Target lesion located in coronary arterial bypass graft ⑦ Target lesion located in the left main coronary artery

Ages Eligible for Study
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Minimum Age: 19 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: FFR-guided stenting<br>Percutaneous coronaryintervention using drug-eluting stent(s) will be performed by FFR-guided strategy. | Procedure: FFR-guided stenting<br>* The percutaneous coronaryintervention using drug-eluting stent will be indicated according to following criteria in the FFR-guided strategy arm * Criteria for revascularization: The FFR ≤ 0.80 will be targeted for PCI<br>|
| Active Comparator: IVUS-guided stenting<br>Percutaneous coronaryintervention using drug-eluting stent(s) will be performed by IVUS-guided strategy. | Procedure: IVUS-guided stenting<br>* The percutaneous coronaryintervention using drug-eluting stent will be indicated according to following criteria in the IVUS-guided strategy arm * Criteria for revascularization: Minimum lumen area (MLA) ≤ 3mm2 or (MLA ≤ 4mm2 AND Plaque burden >70%)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient-oriented composite outcome | a composite of all death, myocardial infarction (MI) or any revascularization | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient-oriented composite outcome | a composite of all death, myocardial infarction (MI) or any | 12 months | 
| Stent-oriented composite endpoint | a composite of cardiac death, target-vessel MI, or target lesion revascularization | 12 months | 
| Stent-oriented composite endpoint | a composite of cardiac death, target-vessel MI, or target lesion revascularization | 24 months | 
| Cost-effectiveness analysis | medical expenses of treatment and follow-up. Cost estimates utilize micro-costing, the total cost by identifying the utilization of medical resources used, and macro-costing, medical expenses resulting from clinical events from health insurance data. | 24 months | 
| All-cause death | death from any cause | 24 months | 
| Cardiac death | death from cardiaccause | 24 months | 
| Target-vessel and all-cause nonfatal myocardial infarction without per-procedural myocardial infarction | Myocardial infarction during 24 months follow-up without periprocedural myocardial infarction | 24 months | 
| Target-vessel and all-cause nonfatal myocardial infarction with per-procedural myocardial infarction | Myocardial infarction during 24 months follow-up with periprocedural myocardial infarction | 24 months | 
| Peri-procedural MI using referred definitions | Number of participants with peri-procedural myocardial infarction after PCI | At discharge (1 week after index procedure) | 
| Target vessel/lesion revascularization | Number of participants and vessels/lesions with ischemia-driven or any reavascularizations at target vessel/lesion | 24 months | 
| Non-target vessel/lesion revascularization | Number of participants and vessels/lesions with ischemia-driven or any reavascularizations at non-target vessel/lesion. | 24 months | 
| Any revascularization | Number of participants and vessels/lesions with ischemia-driven or any revascularizations at any vessel/lesion | 24 months | 
| Academic Research Consortium defined - Stent thrombosis | Number of participants with definite/probable/possible stent thrombosis | 24 months | 
| Stroke | Number of participants with ischemic or hemorrhagic stroke | 24 months | 
| Acute success of procedure | Device-related, lesion-related and procedure-related success of index procedure (residual diameter stenosis<50% and thrombolysis in myocardial infarction flow 3) | immediately after the intervention | 
| Angina severity measured with Seattle Angina Questionnaires | Seattle Angina Questionnaires (physical limitation and angina frequency were classified as minimal: 75-100, mild: 50-74, moderate: 25-49, severe: 0-24) | 12 months | 
| Angina severity measured with Seattle Angina Questionnaires | Seattle Angina Questionnaires (physical limitation and angina frequency were classified as minimal: 75-100, mild: 50-74, moderate: 25-49, severe: 0-24) | 24 months |