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

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)

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.

1. 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.

2. 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.

3. 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%].

4. 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.

5. Extended Outcome Follow-Up Following the 2-year follow-up period, clinical outcomes will also be collected until September 30, 2024, to assess the long-term outcomes of each treatment group.

1. 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

2. 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