Angiography-Derived FFR And IVUS for Clinical Outcomes in Patients With Coronary Artery Disease

Study Overview
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Brief Summary
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Comparison of Angiography-derived Fractional FLow Reserve And IntraVascular Ultrasound-guided Intervention Strategy for Clinical OUtcomes in Patients with CoRonary Artery Disease

Detailed Description
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The primary hypothesis is that angiography-derived FFR-guided strategy for PCI with a drug-eluting stent (DES) will show non-inferiority in rates of patients-oriented composite outcomes (POCO) at 12 months after randomization, compared with IVUS-guided strategy for PCI with a DES in patients with coronary artery disease. Study population and sample size calculation： Sample size calculation based on the event rates of previous trials, investigators predicted the rates of POCO at 12 months after PCI will be 7% in the Angiography-derived FFR-guided arm, and 8% in the IVUS-guided arm Primary endpoint: patient-oriented composite outcome (a composite of all-cause death, MI, any revascularization) at 12 months after PCI Design: non-inferiority, delta = 2.5% Sampling ratio: angiography-derived FFR-guided strategy: IVUS-guided strategy = 1:1 Type I error (α): One-sided 2.5% Accrual time: 3 years Total time: 4 years (accrual 3 years + follow-up 1 years) Assumption: POCO 7.0% vs. 8.0% in angiography-derived FFR or IVUS-guided strategy, respectively Statistical power (1- β): 80% Primary statistical method: Kaplan-Meier survival analysis with log-rank test Estimated attrition rate: total 5% Stratification in Randomization: Presence of diabetes mellitus (35% of patients in each group) Based on the above assumption, we would need total 1,872 patients (936 patients in each group) with consideration of an attrition rate. Research Materials and Indication for Revascularization： For the angiography-derived FFR-guided strategy arm, criteria for revascularization: angiography-derived FFR ≤ 0.80. For the IVUS-guided strategy arm, the criterion for revascularization is MLA ≤ 3mm2 or [3mm2 < MLA ≤ 4mm2 and plaque burden > 70%].

Official Title
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Comparison of Angiography-derived Fractional FLow Reserve- And IntraVascular Ultrasound-guided Intervention Strategy for Clinical OUtcomes in Patients With CoRonary Artery Disease

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Procedure: Angiography-derived FFR
* Procedure: IVUS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ① Subject must be ≥ 18 years. ② Subject is able to verbally confirm understandings of risks, benefits and treatment alternatives of receiving invasive physiologic or imaging evaluation and PCI with a drug-eluting stent (DES) and he/she or his/her legally authorized representative provides written informed consent prior to any study related procedure. ③ Patients suspected with ischemic heart disease. ④ Patients with ≥ 50% stenosis by angiography-based visual estimation eligible for stent implantation. ⑤ Target vessel size ≥ 2.5mm in visual estimation. ⑥ Target vessels are limited to major epicardial coronary arteries (left anterior descending artery[LAD], left circumflex artery [LCX], right coronary artery [RCA]) Exclusion Criteria: ① The patient has a known hypersensitivity or contraindication to any of the following medications: Heparin, Aspirin, Clopidogrel, Prasugrel, Ticagrelor, Contrast media (Patients with documented sensitivity to contrast media which can be effectively premedicated with steroids and diphenhydramine [e.g. rash] may be enrolled.) ② Patients with active pathologic bleeding. ③ Gastrointestinal or genitourinary major bleeding within the prior 3 months. ④ History of bleeding. diathesis, known coagulopathy (including heparin-induced thrombocytopenia). ⑤Non-cardiac co-morbid conditions with life expectancy < 1 year. ⑥ Target vessel total occlusion. ⑦ Target lesion located in coronary arterial bypass graft. ⑧ Left main coronary artery stenosis ≥ 50%. ⑨ Not eligible for angiography-derived FFR (ostial RCA ≥ 50% stenosis, myocardial bridging, severe tortuosity, severe overlap, poor image quality)

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Angiography-derived FFR-guided PCI group<br>Percutaneous coronary intervention using drug-eluting stent(s) will be performed by Angiography-derived FFR-guided strategy | Procedure: Angiography-derived FFR<br>* The percutaneous coronary intervention using drug-eluting stent will be indicated according to following criteria in the Angiography-derived FFR-guided strategy arm *Criteria for revascularization: Angiography-derived FFR ≤ 0.80<br>|
| Active Comparator: IVUS-guided PCI group<br>Percutaneous coronary intervention using drug-eluting stent(s) will be performed by IVUS-guided strategy | Procedure: IVUS<br>* The percutaneous coronary intervention 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 3< MLA ≤ 4mm2 & 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 | Patient-oriented composite outcome (POCO), defined as a composite of all death, myocardial infarction (MI) or any revascularization at 12 months after randomization according to the ARC definitions. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient-oriented composite outcome (POCO) | POCO at 24 and 60 months after randomization according to the ARC consensus | 24, 60 months | 
| Target vessel failure | Target vessel failure (a composite of cardiac death, target-vessel MI, or target vessel revascularization) | 12, 24 and 60 months | 
| Cost-effectiveness analysis | Cost-effectiveness analysis | 12, 24 and 60 months | 
| All-cause and cardiac death | All-cause and cardiac death | 12, 24 and 60 months | 
| Any nonfatal MI without peri-procedural MI | Any nonfatal MI without peri-procedural MI | 12, 24 and 60 months | 
| Any nonfatal MI with peri-procedural MI | Any nonfatal MI with peri-procedural MI | 12, 24 and 60 months | 
| Any target vessel/lesion revascularization | Any target vessel/lesion revascularization | 12, 24 and 60 months | 
| Any non-target vessel/lesion revascularization | Any non-target vessel/lesion revascularization | 12, 24 and 60 months | 
| Any revascularization (ischemia-driven or all) | Any revascularization (ischemia-driven or all) | 12, 24 and 60 months | 
| Stent thrombosis (definite/probable/possible) | Stent thrombosis (definite/probable/possible) | 12, 24 and 60 months | 
| Stroke (ischemic and hemorrhagic) | Stroke (ischemic and hemorrhagic) | 12, 24 and 60 months | 
| Acute success of procedure and rate of PCI optimization | Acute success of procedure and rate of PCI optimization | At discharge (1 week after index procedure) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Angiography-derived fractional flow reserve, Intravascular ultrasound, Percutaneous coronary intervention, Fractional flow reserve