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

Coronary Artery Disease Clinical Trial

— FLAVOUR III  

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)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06218485
• Other study ID #: 2023-0896
• Status: Not yet recruiting
• Phase: N/A
• Start date: March 1, 2024
• Est. completion date: December 1, 2029

Study information

• Verified date: January 2024
• Source: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Contact: Xinyang Hu, MD, PhD
• Phone: +86 0571 87784808
• Email: hxy0507[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 12.0% in the control group (FFR group) and 8.0% 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): Two-sided 5%

• Accrual time: 24 months

• Total time: 7 years (accrual 24 months + follow-up 60 months)

• Assumption: POCO 12.0% vs. 8.0% in control or experimental group, respectively

• Statistical power (1- β): 80%

• 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 1,936 patients (968 patients in each group) with consideration of an attrition rate.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 1936
• Est. completion date: December 1, 2029
• Est. primary completion date: December 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Procedure:
• 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: 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: ? Plaque burden at stent edge =55%; ? Minimal stent area = 5.5 mm2, or minimal stent area = distal reference lumen area
• Fractional flow reserve-guided PCI strategy
The percutaneous coronary intervention will be performed by fractional flow reserve (FFR)-guided strategy: 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: ? Post-PCI FFR = 0.88, or ? Post-PCI ?FFR ([FFR at stent distal edge] - [FFR at stent proximal edge]) < 0.05

Locations

Country	Name	City	State
China	Peking University Third Hospital	Beijing
China	Second Affiliated Hospital of Shantou University Medical College	Guangdong
China	The Affiliated Hospital of Hangzhou Normal University	Hangzhou
China	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou
China	Changxing People's Hospital	Huzhou
China	The Affiliated Hospital of Shandong University of TCM	Jinan
China	The Fourth People's Hospital of Jinan	Jinan
China	Jinhua Central Hospital	Jinhua
China	First Affiliated Hospital of Kunming Medical University	Kunming
China	The First Affiliated Hospital of Nanchang University	Nanchang
China	Ningbo Medical Center Lihuili Hospital	Ningbo
China	The Affiliated Hospital of Medical College, Ningbo University	Ningbo
China	Renji Hospital Shanghai Jiaotong University School of Medicine	Shanghai
China	The First Affiliated hospital of Wenzhou Medical University	Wenzhou
Korea, Republic of	Bucheon Sejong Hospital	Bucheon
Korea, Republic of	Inje University Haeundae Paik Hospital	Busan
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Chonnam National University Hospital	Donggu
Korea, Republic of	Inje University Ilsan Paik Hospital	Goyang
Korea, Republic of	Seoul National University Hospital,	Seoul
Korea, Republic of	Seoul ST. Mary's Hospital	Seoul
Korea, Republic of	Uijeongbu Eulji Medical Center	Uijeongbu
Korea, Republic of	Ulsan University Hospital	Ulsan
Korea, Republic of	Yonsei University Wonju Severance Hospital	Wonju

Sponsors (25)

Lead Sponsor

Collaborator

Second Affiliated Hospital, School of Medicine, Zhejiang University

Bucheon Sejong Hospital, Changxing People's Hospital, Chonnam National University Hospital, First Affiliated Hospital of Kunming Medical University, First Affiliated Hospital of Wenzhou Medical University, Inje University Haeundae Paik Hospital, Inje University Ilsan Paik Hospital, Jinhua Central Hospital, Keimyung University Dongsan Medical Center, Kyungpook National University Hospital, Ningbo Medical Center Lihuili Hospital, Peking University Third Hospital, RenJi Hospital, Second Affiliated Hospital of Shantou University Medical College, Seoul National University Hospital, Seoul St. Mary's Hospital, Shandong University of Traditional Chinese Medicine, The Affiliated Hospital of Hangzhou Normal University, The Affiliated Hospital of Medical College, Ningbo University, The First Affiliated Hospital of Nanchang University, The Fourth People's Hospital of Jinan, Uijeongbu Eulji Medical Center, Ulsan University Hospital, Yonsei University Wonju Severance Hospital

Countries where clinical trial is conducted

China,  Korea, Republic of, 

References & Publications (10)

Collet C, Onuma Y, Sonck J, Asano T, Vandeloo B, Kornowski R, Tu S, Westra J, Holm NR, Xu B, de Winter RJ, Tijssen JG, Miyazaki Y, Katagiri Y, Tenekecioglu E, Modolo R, Chichareon P, Cosyns B, Schoors D, Roosens B, Lochy S, Argacha JF, van Rosendael A, Bax J, Reiber JHC, Escaned J, De Bruyne B, Wijns W, Serruys PW. Diagnostic performance of angiography-derived fractional flow reserve: a systematic review and Bayesian meta-analysis. Eur Heart J. 2018 Sep 14;39(35):3314-3321. doi: 10.1093/eurheartj/ehy445. Erratum In: Eur Heart J. 2019 Jan 21;40(4):356. — View Citation

De Maria GL, Garcia-Garcia HM, Scarsini R, Hideo-Kajita A, Gonzalo Lopez N, Leone AM, Sarno G, Daemen J, Shlofmitz E, Jeremias A, Tebaldi M, Bezerra HG, Tu S, Lemos PA, Ozaki Y, Dan K, Collet C, Banning AP, Barbato E, Johnson NP, Waksman R. Novel Indices of Coronary Physiology: Do We Need Alternatives to Fractional Flow Reserve? Circ Cardiovasc Interv. 2020 Apr;13(4):e008487. doi: 10.1161/CIRCINTERVENTIONS.119.008487. Epub 2020 Apr 16. Erratum In: Circ Cardiovasc Interv. 2020 Jun;13(6):e000071. — View Citation

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. — View Citation

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 Engl J Med. 2017 May 11;376(19):1813-1823. doi: 10.1056/NEJMoa1616540. Epub 2017 Mar 18. — View Citation

Kogame N, Ono M, Kawashima H, Tomaniak M, Hara H, Leipsic J, Andreini D, Collet C, Patel MR, Tu S, Xu B, Bourantas CV, Lerman A, Piek JJ, Davies JE, Escaned J, Wijns W, Onuma Y, Serruys PW. The Impact of Coronary Physiology on Contemporary Clinical Decisi — View Citation

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. — View Citation

Raber L, Mintz GS, Koskinas KC, Johnson TW, Holm NR, Onuma Y, Radu MD, Joner M, Yu B, Jia H, Meneveau N, de la Torre Hernandez JM, Escaned J, Hill J, Prati F, Colombo A, di Mario C, Regar E, Capodanno D, Wijns W, Byrne RA, Guagliumi G; ESC Scientific Document Group. Clinical use of intracoronary imaging. Part 1: guidance and optimization of coronary interventions. An expert consensus document of the European Association of Percutaneous Cardiovascular Interventions. Eur Heart J. 2018 Sep 14;39(35):3281-3300. doi: 10.1093/eurheartj/ehy285. Erratum In: Eur Heart J. 2019 Jan 14;40(3):308. — View Citation

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. — View Citation

Writing Committee Members; Lawton JS, Tamis-Holland JE, Bangalore S, Bates ER, Beckie TM, Bischoff JM, Bittl JA, Cohen MG, DiMaio JM, Don CW, Fremes SE, Gaudino MF, Goldberger ZD, Grant MC, Jaswal JB, Kurlansky PA, Mehran R, Metkus TS Jr, Nnacheta LC, Rao — View Citation

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Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Patient-oriented composite outcome	Patient-oriented composite outcome (POCO), defined as a composite of all death, myocardial infarction (MI), or any revascularization at 24 months after randomization.	24 months
Secondary	Patient-oriented composite outcome at 60 months	Patient-oriented composite outcome (POCO), defined as a composite of all death, myocardial infarction (MI), or any revascularization.	60 months
Secondary	Individual component of Patient-oriented composite outcome	Individual component of Patient-oriented composite outcome (death, myocardial infarction, revascularization).	24 and 60 months
Secondary	Target vessel failure	Target vessel failure, defined as a composite of cardiac death, target-vessel MI, or target vessel revascularization.	24 and 60 months
Secondary	Cost-effectiveness analysis	Incremental cost effectiveness ratio (ICER).	24 and 60 months
Secondary	All-cause and cardiac death	All-cause and cardiac death.	24 and 60 months
Secondary	Any nonfatal myocardial infarction without peri-procedural myocardial infarction	Any nonfatal myocardial infarction without peri-procedural myocardial infarction.	24 and 60 months
Secondary	Any nonfatal myocardial infarction with peri-procedural myocardial infarction	Any nonfatal myocardial infarction with peri-procedural myocardial infarction.	24 and 60 months
Secondary	Any target vessel/lesion revascularization	Any target vessel/lesion revascularization.	24 and 60 months
Secondary	Any non-target vessel/lesion revascularization	Any non-target vessel/lesion revascularization.	24 and 60 months
Secondary	Any revascularization (ischemia-driven or all)	Any revascularization (ischemia-driven or all).	24 and 60 months
Secondary	Stent thrombosis (definite/probable/possible)	Stent thrombosis at 24 and 60 months after randomization.	24 and 60 months
Secondary	Stroke (ischemic and hemorrhagic)	Stroke at 24 and 60 months after randomization.	24 and 60 months