Clinical trial NCT06218485: FFR Versus IVUS with Angiography-Derived FFR for Clinical Outcomes in Patients with Coronary Artery Disease
Official title: Comparison of Fractional Flow Reserve-Guided Strategy Versus Intravascular Ultrasound-Guided Stent Implantation After Angiography-Derived Fractional Flow Reserve-based Decision-Making (The FLAVOUR III Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Coronary Artery Disease
Keywords: Angiography-derived fractional flow reserve
Intravascular ultrasound
Fractional flow reserve
Percutaneous coronary intervention
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
Collaborators: name: Seoul National University Hospital
name: Peking University Third Hospital
name: RenJi Hospital
name: Second Affiliated Hospital of Shantou University Medical College
name: The First Affiliated Hospital of Nanchang University
name: First Affiliated Hospital of Kunming Medical University
name: The Fourth People's Hospital of Jinan
name: Jinhua Central Hospital
name: The Affiliated Hospital of Hangzhou Normal University
name: Changxing People's Hospital
name: First Affiliated Hospital of Wenzhou Medical University
name: The Affiliated Hospital of Medical College, Ningbo University
name: Keimyung University Dongsan Medical Center
name: Inje University Ilsan Paik Hospital
name: Ulsan University Hospital
name: Uijeongbu Eulji Medical Center
name: Kyungpook National University Hospital
name: Seoul St. Mary's Hospital
name: Yonsei University Wonju Severance Hospital
name: Inje University Haeundae Paik Hospital
name: Sejong General Hospital
name: Chonnam National University Hospital
name: Ningbo Medical Center Lihuili Hospital
name: Shandong University of Traditional Chinese Medicine
First posted: 2024-01-23
Enrollment: 1942
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment
Primary purpose: TREATMENT

Brief summary: To compare the clinical outcomes of fractional flow reserve (FFR)-guided strategy versus intravascular ultrasound (IVUS)-guided stent implantation after angiography-derived FFR-based decision-making.

Detailed description: 1. Hypothesis: The IVUS-guided stent implantation after angiography-derived FFR-based decision-making will show superiority in terms of a lower rate of patients-oriented composite outcomes (POCO) at 24 months after randomization compared with the FFR-guided PCI strategy in patients with coronary stenosis.
2. Research materials and indication for revascularization:

   2.1 Experimental group: PCI will be performed if angiography-derived FFR ≤0.80 and will be deferred if angiography-derived FFR \>0.80; If PCI is performed, PCI optimization using IVUS will be performed following the recommended criteria: ① Plaque burden at stent edge ≤55%; ② Minimal stent area ≥ 5.5 mm2, or minimal stent area ≥ distal reference lumen area.

   2.2 Control group: PCI will be performed if FFR ≤0.80 and will be deferred if FFR \>0.80; If PCI is performed, PCI optimization using FFR will be performed following the recommended criteria: ① Post-PCI FFR ≥ 0.88, or ② Post-PCI ΔFFR (\[FFR at stent distal edge\] - \[FFR at stent proximal edge\]) \< 0.05.
3. Sample size: In the post-hoc analysis of the FLAVOUR I study applying QFR analysis, the 2-year POCO rate was 13.0% in the PCI group with FFR ≤0.80 and undergoing FFR-based PCI optimization and 7.1% in the PCI group with QFR ≤0.80 and undergoing IVUS-based PCI optimization. Meanwhile, the 2-year POCO rate was 5.8% and 6.5% in the deferral of PCI group with FFR \>0.80 and QFR \>0.80, respectively. Assuming a PCI rate of 70% in patients with coronary artery lesions with 50-90% stenosis that is the inclusion criteria for the current study, and considering event rates from historical studies evaluating FFR- and QFR-guided PCI strategies, the cumulative incidence rate of POCO at 24 months was estimated to be 13.0% in the control group (FFR group) and 9.0% in the experimental group (QFR-IVUS group).

   * Primary endpoint: POCO, defined as a composite of death from any cause, MI, or any revascularization at 24 months after randomization.
   * Design: superiority
   * Sampling ratio: experimental group : control group = 1:1
   * Type I error (α): One-sided 2.5%
   * Accrual time: 24 months
   * Total time: 4 years (accrual 24 months + follow-up 24 months)
   * Assumption: POCO 13.0% vs. 9.0% in control or experimental group, respectively
   * Statistical power (1- β): 90%
   * Primary statistical method: Kaplan-Meier survival analysis with log-rank test
   * Estimated attrition rate: total 10%
   * Stratification in randomization: Presence of diabetes mellitus

Based on the above assumption, we would need total 1,942 patients (971 patients in each group) with consideration of an attrition rate.

Eligibility criteria: Inclusion Criteria:

* Subject must be ≥ 19 years.
* Subject is able to verbally confirm understanding 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.
* Subjects suspected with ischemic heart disease.
* Subjects with coronary artery diameter stenosis 50-90% by angiography-based visual estimation eligible for stent implantation.
* Target vessel size ≥ 2.5mm in visual estimation.

Exclusion Criteria:

* Known hypersensitivity or contraindication to any of the following medications: Heparin, Aspirin, Clopidogrel, Prasugrel, Ticagrelor
* Active pathologic bleeding.
* Gastrointestinal or genitourinary major bleeding within the prior 3 months.
* History of bleeding diathesis, known coagulopathy.
* Non-cardiac co-morbid conditions with life expectancy \< 2 years.
* Target lesion located in coronary arterial bypass graft.
* Left main coronary artery stenosis ≥ 50%.
* Chronic total occlusion in the study target vessel.
* Culprit lesion of ST-elevation myocardial infarction (STEMI).
* Not eligible for angiography-derived FFR (ostial RCA ≥ 50% stenosis, severe tortuosity, severe overlap, poor image quality).

Primary outcomes:
measure: Patient-oriented composite outcome
timeFrame: 24 months
Secondary outcomes:
measure: Patient-oriented composite outcome at 60 months
timeFrame: 60 months
measure: Individual component of Patient-oriented composite outcome
timeFrame: 24 and 60 months
measure: Target vessel failure
timeFrame: 24 and 60 months
measure: Cost-effectiveness analysis
timeFrame: 24 and 60 months
measure: All-cause and cardiac death
timeFrame: 24 and 60 months
measure: Any nonfatal myocardial infarction without peri-procedural myocardial infarction
timeFrame: 24 and 60 months
measure: Any nonfatal myocardial infarction with peri-procedural myocardial infarction
timeFrame: 24 and 60 months
measure: Any target vessel/lesion revascularization
timeFrame: 24 and 60 months
measure: Any non-target vessel/lesion revascularization
timeFrame: 24 and 60 months
measure: Any revascularization (ischemia-driven or all)
timeFrame: 24 and 60 months
measure: Stent thrombosis (definite/probable/possible)
timeFrame: 24 and 60 months
measure: Stroke (ischemic and hemorrhagic)
timeFrame: 24 and 60 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Third Hospital
city: Guangdong
country: China
facility: Second Affiliated Hospital of Shantou University Medical College
city: Hangzhou
country: China
facility: The Affiliated Hospital of Hangzhou Normal University
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University School of Medicine
city: Huzhou
country: China
facility: Changxing People's Hospital
city: Jinan
country: China
facility: The Affiliated Hospital of Shandong University of TCM
city: Jinan
country: China
facility: The Fourth People's Hospital of Jinan
city: Jinhua
country: China
facility: Jinhua Central Hospital
city: Kunming
country: China
facility: First Affiliated Hospital of Kunming Medical University
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
city: Ningbo
country: China
facility: Ningbo Medical Center Lihuili Hospital
city: Ningbo
country: China
facility: The Affiliated Hospital of Medical College, Ningbo University
city: Shanghai
country: China
facility: Renji Hospital Shanghai Jiaotong University School of Medicine
city: Wenzhou
country: China
facility: The First Affiliated hospital of Wenzhou Medical University
city: Bucheon
country: Korea, Republic of
facility: Bucheon Sejong Hospital
city: Busan
country: Korea, Republic of
facility: Inje University Haeundae Paik Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Donggu
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Goyang
country: Korea, Republic of
facility: Inje University Ilsan Paik Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital,
city: Seoul
country: Korea, Republic of
facility: Seoul ST. Mary's Hospital
city: Uijeongbu
country: Korea, Republic of
facility: Uijeongbu Eulji Medical Center
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Wonju
country: Korea, Republic of
facility: Yonsei University Wonju Severance Hospital
Study officials:
affiliation: Second Affiliated Hospital, School of Medicine, Zhejiang University
name: Jian'an Wang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Seoul National University Hospital
name: Bon-Kwon Koo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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