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

Официальное название

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)

Обзор

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.

Подробное описание

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.

Вмешательства

• Процедура Intravascular ultrasound-guided stent implantation after angiography-derived FFR-based decision-making
  The percutaneous coronary intervention will be performed by intravascular ultrasound (IVUS)-guided strategy after angiography-derived FFR-based decision-making: 1. PCI will be performed if angiography-derived FFR ≤0.80 and will be deferred if angiography-derived FFR \>0.80. 2. 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 are
• Процедура Fractional flow reserve-guided PCI strategy
  The percutaneous coronary intervention will be performed by fractional flow reserve (FFR)-guided strategy: 1. PCI will be performed if FFR ≤0.80 and will be deferred if FFR \>0.80. 2. 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

Первичные конечные точки

• Patient-oriented composite outcome [Срок оценки: 24 months]

Вторичные конечные точки (12)

• Patient-oriented composite outcome at 60 months [Срок оценки: 60 months]
• Individual component of Patient-oriented composite outcome [Срок оценки: 24 and 60 months]
• Target vessel failure [Срок оценки: 24 and 60 months]
• Cost-effectiveness analysis [Срок оценки: 24 and 60 months]
• All-cause and cardiac death [Срок оценки: 24 and 60 months]
• Any nonfatal myocardial infarction without peri-procedural myocardial infarction [Срок оценки: 24 and 60 months]
• Any nonfatal myocardial infarction with peri-procedural myocardial infarction [Срок оценки: 24 and 60 months]
• Any target vessel/lesion revascularization [Срок оценки: 24 and 60 months]
• Any non-target vessel/lesion revascularization [Срок оценки: 24 and 60 months]
• Any revascularization (ischemia-driven or all) [Срок оценки: 24 and 60 months]
• Stent thrombosis (definite/probable/possible) [Срок оценки: 24 and 60 months]
• Stroke (ischemic and hemorrhagic) [Срок оценки: 24 and 60 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 14 центров

• Peking University Third Hospital — Пекин
• Second Affiliated Hospital of Shantou University Medical College — Guangdong
• The Affiliated Hospital of Hangzhou Normal University — Ханчжоу
• The Second Affiliated Hospital of Zhejiang University School of Medicine — Ханчжоу
• Changxing People's Hospital — Huzhou
• The Affiliated Hospital of Shandong University of TCM — Цзинань
• The Fourth People's Hospital of Jinan — Цзинань
• Jinhua Central Hospital — Jinhua
• … и ещё 6 центров

South Korea · 11 центров

• Bucheon Sejong Hospital — Bucheon-si
• Inje University Haeundae Paik Hospital — Busan
• Keimyung University Dongsan Medical Center — Daegu
• Kyungpook National University Hospital — Daegu
• Chonnam National University Hospital — Donggu
• Inje University Ilsan Paik Hospital — Goyang
• Seoul National University Hospital, — Seoul
• Seoul ST. Mary's Hospital — Seoul
• … и ещё 3 центра

Публикации

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• Scoccia A, Tomaniak M, Neleman T, Groenland FTW, Plantes ACZD, Daemen J. Angiography-Based Fractional Flow Reserve: State of the Art. Curr Cardiol Rep. 2022 Jun;24(6):667-678. doi: 10.1007/s11886-022-01687-4. Epub 2022 Apr 18. PMID 35435570
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• Fearon WF, Achenbach S, Engstrom T, Assali A, Shlofmitz R, Jeremias A, Fournier S, Kirtane AJ, Kornowski R, Greenberg G, Jubeh R, Kolansky DM, McAndrew T, Dressler O, Maehara A, Matsumura M, Leon MB, De Bruyne B; FAST-FFR Study Investigators. Accuracy of Fractional Flow Reserve Derived From Coronary Angiography. Circulation. 2019 Jan 22;139(4):477-484. doi: 10.1161/CIRCULATIONAHA.118.037350. PMID 30586699
• Xu B, Tu S, Qiao S, Qu X, Chen Y, Yang J, Guo L, Sun Z, Li Z, Tian F, Fang W, Chen J, Li W, Guan C, Holm NR, Wijns W, Hu S. Diagnostic Accuracy of Angiography-Based Quantitative Flow Ratio Measurements for Online Assessment of Coronary Stenosis. J Am Coll Cardiol. 2017 Dec 26;70(25):3077-3087. doi: 10.1016/j.jacc.2017.10.035. Epub 2017 Oct 31. PMID 29101020
• Koo BK, Hu X, Kang J, Zhang J, Jiang J, Hahn JY, Nam CW, Doh JH, Lee BK, Kim W, Huang J, Jiang F, Zhou H, Chen P, Tang L, Jiang W, Chen X, He W, Ahn SG, Yoon MH, Kim U, Lee JM, Hwang D, Ki YJ, Shin ES, Kim HS, Tahk SJ, Wang J; FLAVOUR Investigators. Fractional Flow Reserve or Intravascular Ultrasonography to Guide PCI. N Engl J Med. 2022 Sep 1;387(9):779-789. doi: 10.1056/NEJMoa2201546. PMID 36053504
• Gotberg M, Christiansen EH, Gudmundsdottir IJ, Sandhall L, Danielewicz M, Jakobsen L, Olsson SE, Ohagen P, Olsson H, Omerovic E, Calais F, Lindroos P, Maeng M, Todt T, Venetsanos D, James SK, Karegren A, Nilsson M, Carlsson J, Hauer D, Jensen J, Karlsson AC, Panayi G, Erlinge D, Frobert O; iFR-SWEDEHEART Investigators. Instantaneous Wave-free Ratio versus Fractional Flow Reserve to Guide PCI. N En PMID 28317438

Идентификаторы

NCT: NCT06218485 · 2023-0896

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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