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

Stable Angina Clinical Trial

— FLAVOUR  

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02673424
• Other study ID #: NCT02673424
• Status: Active, not recruiting
• Phase: N/A
• Start date: June 2016
• Est. completion date: January 2022

Study information

• Verified date: May 2020
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1700
• Est. completion date: January 2022
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

1. Inclusion Criteria

• Subject must be = 19 years ? 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 ? Patients with intermediate degree of stenosis (40-70% stenosis by visual estimation) eligible for stent implantation who need FFR or IVUS for further evaluation ? 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) ? Non-cardiac co-morbid conditions with life expectancy < 2 years ? Target lesion located in coronary arterial bypass graft ? Target lesion located in the left main coronary artery

Related Conditions & MeSH terms

• Angina, Stable
• Stable Angina

Intervention

Procedure:
• FFR-guided stenting
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
• IVUS-guided stenting
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%)

Locations

Country	Name	City	State
China	The Second Affiliated Hospital, School of Medicine, Zhejiang University	Zhejiang
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	Inje University Ilsan Paik Hospital	Goyang
Korea, Republic of	Samsung Medical Center, Sungkyunkwan University School of Medicine	Seoul
Korea, Republic of	Seoul National University Hospital, Seoul, Korea	Seoul

Sponsors (8)

Lead Sponsor	Collaborator
Seoul National University Hospital	Ajou University School of Medicine, Inje University, KangWon National University Hospital, Keimyung University Dongsan Medical Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Second Affiliated Hospital, School of Medicine, Zhejiang University, Ulsan University Hospital

Countries where clinical trial is conducted

China,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Patient-oriented composite outcome	a composite of all death, myocardial infarction (MI) or any revascularization	24 months
Secondary	Patient-oriented composite outcome	a composite of all death, myocardial infarction (MI) or any	12 months
Secondary	Stent-oriented composite endpoint	a composite of cardiac death, target-vessel MI, or target lesion revascularization	12 months
Secondary	Stent-oriented composite endpoint	a composite of cardiac death, target-vessel MI, or target lesion revascularization	24 months
Secondary	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
Secondary	All-cause death	death from any cause	24 months
Secondary	Cardiac death	death from cardiaccause	24 months
Secondary	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
Secondary	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
Secondary	Peri-procedural MI using referred definitions	Number of participants with peri-procedural myocardial infarction after PCI	At discharge (1 week after index procedure)
Secondary	Target vessel/lesion revascularization	Number of participants and vessels/lesions with ischemia-driven or any reavascularizations at target vessel/lesion	24 months
Secondary	Non-target vessel/lesion revascularization	Number of participants and vessels/lesions with ischemia-driven or any reavascularizations at non-target vessel/lesion.	24 months
Secondary	Any revascularization	Number of participants and vessels/lesions with ischemia-driven or any revascularizations at any vessel/lesion	24 months
Secondary	Academic Research Consortium defined - Stent thrombosis	Number of participants with definite/probable/possible stent thrombosis	24 months
Secondary	Stroke	Number of participants with ischemic or hemorrhagic stroke	24 months
Secondary	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
Secondary	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
Secondary	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