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

Coronary Artery Disease Clinical Trial

— FLAVOUR II  

Official title:

Comparison of Angiography-derived Fractional FLow Reserve- And IntraVascular Ultrasound-guided Intervention Strategy for Clinical OUtcomes in Patients With CoRonary Artery Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04397211
• Other study ID #: 2019-303
• Status: Active, not recruiting
• Phase: N/A
• Start date: May 29, 2020
• Est. completion date: September 2028

Study information

• Verified date: January 2024
• Source: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Comparison of Angiography-derived Fractional FLow Reserve And IntraVascular Ultrasound-guided Intervention Strategy for Clinical OUtcomes in Patients with CoRonary Artery Disease

Description:

1. The primary hypothesis is that angiography-derived FFR-guided strategy for PCI with a drug-eluting stent (DES) will show non-inferiority in rates of patients-oriented composite outcomes (POCO) at 12 months after randomization, compared with IVUS-guided strategy for PCI with a DES in patients with coronary artery disease.

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 12 months after PCI will be 7% in the Angiography-derived FFR-guided arm, and 8% in the IVUS-guided arm

• Primary endpoint: patient-oriented composite outcome (a composite of all-cause death, MI, any revascularization) at 12 months after PCI

• Design: non-inferiority, delta = 2.5%

• Sampling ratio: angiography-derived FFR-guided strategy: IVUS-guided strategy = 1:1

• Type I error (α): One-sided 2.5%

• Accrual time: 3 years

• Total time: 4 years (accrual 3 years + follow-up 1 years)

• Assumption: POCO 7.0% vs. 8.0% in angiography-derived FFR or IVUS-guided strategy, respectively

• Statistical power (1- β): 80%

• Primary statistical method: Kaplan-Meier survival analysis with log-rank test

• Estimated attrition rate: total 5%

• Stratification in Randomization: Presence of diabetes mellitus (35% of patients in each group) Based on the above assumption, we would need total 1,872 patients (936 patients in each group) with consideration of an attrition rate.

3. Research Materials and Indication for Revascularization： For the angiography-derived FFR-guided strategy arm, criteria for revascularization: angiography-derived FFR ≤ 0.80. For the IVUS-guided strategy arm, the criterion for revascularization is MLA ≤ 3mm2 or [3mm2 < MLA ≤ 4mm2 and plaque burden > 70%].

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1872
• Est. completion date: September 2028
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• ? Subject must be = 18 years. ? Subject is able to verbally confirm understandings 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 prior to any study related procedure. ? Patients suspected with ischemic heart disease. ? Patients with = 50% stenosis by angiography-based visual estimation eligible for stent implantation. ? Target vessel size = 2.5mm in visual estimation. ? Target vessels are limited to major epicardial coronary arteries (left anterior descending artery[LAD], left circumflex artery [LCX], right coronary artery [RCA])

Exclusion Criteria:

• ? The patient has a known hypersensitivity or contraindication to any of the following medications: Heparin, Aspirin, Clopidogrel, Prasugrel, Ticagrelor, Contrast media (Patients with documented sensitivity to contrast media which can be effectively premedicated with steroids and diphenhydramine [e.g. rash] may be enrolled.) ? Patients with 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 < 1 year. ? Target vessel total occlusion. ? Target lesion located in coronary arterial bypass graft. ? Left main coronary artery stenosis = 50%. ? Not eligible for angiography-derived FFR (ostial RCA = 50% stenosis, myocardial bridging, severe tortuosity, severe overlap, poor image quality)

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Procedure:
• Angiography-derived FFR
The percutaneous coronary intervention using drug-eluting stent will be indicated according to following criteria in the Angiography-derived FFR-guided strategy arm *Criteria for revascularization: Angiography-derived FFR = 0.80
• IVUS
The percutaneous coronary intervention 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 3< MLA = 4mm2 & Plaque burden > 70%

Locations

Country	Name	City	State
China	Peking University Third Hospital	Beijing
China	Second Affiliated Hospital of Shantou University Medical College	Guangdong
China	Affiliated Hangzhou First People's Hospital	Hangzhou
China	Second Affiliated Hospital, School of Medicine, Zhejiang University, China	Hangzhou	Zhejiang
China	The Affiliated Hospital of Hangzhou Normal University	Hangzhou
China	Zhejiang Greentown Cardiovascular Hospital	Hangzhou
China	Changxing People's Hospital	Huzhou
China	Huzhou Central Hospital	Huzhou
China	The Fourth People's Hospital of Jinan	Jinan
China	Dongyang People's Hospital	Jinhua
China	Jinhua Central Hospital	Jinhua
China	First Affiliated Hospital of Kunming Medical University	Kunming
China	The First Affiliated Hospital of Nanchang University	Nanchang
China	The Affiliated Hospital of Medical College, Ningbo University	Ningbo
China	Shandong Jining No.1 People's Hospital	Shandong
China	Shandong University of Traditional Chinese Medicine	Shandong
China	Renji Hospital Shanghai Jiaotong University School of Medicine	Shanghai
China	Second hospital of Shanxi Medical University	Taiyuan
China	The first affiliated hospital of Wenzhou Medical University	Wenzhou
China	The second affiliated hospital of Wenzhou Medical University	Wenzhou
China	Zhongnan Hospital of Wuhan University	Wuhan
Korea, Republic of	Seoul National University Hospital,	Seoul
Korea, Republic of	Ulsan University Hospital	Ulsan

Sponsors (23)

Lead Sponsor

Collaborator

Second Affiliated Hospital, School of Medicine, Zhejiang University

Affiliated Hangzhou First People's Hospital, Changxing People's Hospital, Dongyang People's Hospital, First Affiliated Hospital of Kunming Medical University, First Affiliated Hospital of Wenzhou Medical University, Huizhou Municipal Central Hospital, Jinhua Central Hospital, Jining First People's Hospital, Peking University Third Hospital, RenJi Hospital, Second Affiliated Hospital of Shantou University Medical College, Second Affiliated Hospital of Wenzhou Medical University, Second Hospital of Shanxi Medical University, Seoul National University 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, Ulsan University Hospital, Wuhan University, Zhejiang Greentown Cardiovascular Hospital

Countries where clinical trial is conducted

China,  Korea, Republic of, 

References & Publications (21)

Ahn JM, Kang SJ, Yoon SH, Park HW, Kang SM, Lee JY, Lee SW, Kim YH, Lee CW, Park SW, Mintz GS, Park SJ. Meta-analysis of outcomes after intravascular ultrasound-guided versus angiography-guided drug-eluting stent implantation in 26,503 patients enrolled i — View Citation

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, Ba — View Citation

Davies JE, Sen S, Dehbi HM, Al-Lamee R, Petraco R, Nijjer SS, Bhindi R, Lehman SJ, Walters D, Sapontis J, Janssens L, Vrints CJ, Khashaba A, Laine M, Van Belle E, Krackhardt F, Bojara W, Going O, Harle T, Indolfi C, Niccoli G, Ribichini F, Tanaka N, Yokoi — View Citation

De Bruyne B, Fearon WF, Pijls NH, Barbato E, Tonino P, Piroth Z, Jagic N, Mobius-Winckler S, Rioufol G, Witt N, Kala P, MacCarthy P, Engstrom T, Oldroyd K, Mavromatis K, Manoharan G, Verlee P, Frobert O, Curzen N, Johnson JB, Limacher A, Nuesch E, Juni P; — 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 — View Citation

Fujii K, Carlier SG, Mintz GS, Yang YM, Moussa I, Weisz G, Dangas G, Mehran R, Lansky AJ, Kreps EM, Collins M, Stone GW, Moses JW, Leon MB. Stent underexpansion and residual reference segment stenosis are related to stent thrombosis after sirolimus-elutin — View Citation

Garcia-Garcia HM, McFadden EP, Farb A, Mehran R, Stone GW, Spertus J, Onuma Y, Morel MA, van Es GA, Zuckerman B, Fearon WF, Taggart D, Kappetein AP, Krucoff MW, Vranckx P, Windecker S, Cutlip D, Serruys PW; Academic Research Consortium. Standardized End P — View Citation

ISCHEMIA Trial Research Group; Maron DJ, Hochman JS, O'Brien SM, Reynolds HR, Boden WE, Stone GW, Bangalore S, Spertus JA, Mark DB, Alexander KP, Shaw L, Berger JS, Ferguson TB Jr, Williams DO, Harrington RA, Rosenberg Y. International Study of Comparativ — View Citation

Kang J, Koo BK, Hu X, Lee JM, Hahn JY, Yang HM, Shin ES, Nam CW, Doh JH, Lee BK, Ahn C, Wang J, Tahk SJ. Comparison of Fractional FLow Reserve And Intravascular ultrasound-guided Intervention Strategy for Clinical OUtcomes in Patients with InteRmediate St — View Citation

Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, Chambers CE, Ellis SG, Guyton RA, Hollenberg SM, Khot UN, Lange RA, Mauri L, Mehran R, Moussa ID, Mukherjee D, Nallamothu BK, Ting HH; American College of Cardiology Foundation; American — View Citation

Maron DJ, Hochman JS, Reynolds HR, Bangalore S, O'Brien SM, Boden WE, Chaitman BR, Senior R, Lopez-Sendon J, Alexander KP, Lopes RD, Shaw LJ, Berger JS, Newman JD, Sidhu MS, Goodman SG, Ruzyllo W, Gosselin G, Maggioni AP, White HD, Bhargava B, Min JK, Man — View Citation

Melikian N, De Bondt P, Tonino P, De Winter O, Wyffels E, Bartunek J, Heyndrickx GR, Fearon WF, Pijls NH, Wijns W, De Bruyne B. Fractional flow reserve and myocardial perfusion imaging in patients with angiographic multivessel coronary artery disease. JAC — View Citation

Nam CW, Yoon HJ, Cho YK, Park HS, Kim H, Hur SH, Kim YN, Chung IS, Koo BK, Tahk SJ, Fearon WF, Kim KB. Outcomes of percutaneous coronary intervention in intermediate coronary artery disease: fractional flow reserve-guided versus intravascular ultrasound-g — View Citation

Park KW, Kang SH, Yang HM, Lee HY, Kang HJ, Cho YS, Youn TJ, Koo BK, Chae IH, Kim HS. Impact of intravascular ultrasound guidance in routine percutaneous coronary intervention for conventional lesions: data from the EXCELLENT trial. Int J Cardiol. 2013 Au — View Citation

Pijls NH, van Schaardenburgh P, Manoharan G, Boersma E, Bech JW, van't Veer M, Bar F, Hoorntje J, Koolen J, Wijns W, de Bruyne B. Percutaneous coronary intervention of functionally nonsignificant stenosis: 5-year follow-up of the DEFER Study. J Am Coll Ca — View Citation

Tu S, Westra J, Yang J, von Birgelen C, Ferrara A, Pellicano M, Nef H, Tebaldi M, Murasato Y, Lansky A, Barbato E, van der Heijden LC, Reiber JHC, Holm NR, Wijns W; FAVOR Pilot Trial Study Group. Diagnostic Accuracy of Fast Computational Approaches to Der — View Citation

Westra J, Andersen BK, Campo G, Matsuo H, Koltowski L, Eftekhari A, Liu T, Di Serafino L, Di Girolamo D, Escaned J, Nef H, Naber C, Barbierato M, Tu S, Neghabat O, Madsen M, Tebaldi M, Tanigaki T, Kochman J, Somi S, Esposito G, Mercone G, Mejia-Renteria H — View Citation

Westra J, Tu S, Campo G, Qiao S, Matsuo H, Qu X, Koltowski L, Chang Y, Liu T, Yang J, Andersen BK, Eftekhari A, Christiansen EH, Escaned J, Wijns W, Xu B, Holm NR. Diagnostic performance of quantitative flow ratio in prospectively enrolled patients: An in — View Citation

Westra J, Tu S, Winther S, Nissen L, Vestergaard MB, Andersen BK, Holck EN, Fox Maule C, Johansen JK, Andreasen LN, Simonsen JK, Zhang Y, Kristensen SD, Maeng M, Kaltoft A, Terkelsen CJ, Krusell LR, Jakobsen L, Reiber JHC, Lassen JF, Bottcher M, Botker HE — View Citation

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 — View Citation

Zhang J, Gao X, Kan J, Ge Z, Han L, Lu S, Tian N, Lin S, Lu Q, Wu X, Li Q, Liu Z, Chen Y, Qian X, Wang J, Chai D, Chen C, Li X, Gogas BD, Pan T, Shan S, Ye F, Chen SL. Intravascular Ultrasound Versus Angiography-Guided Drug-Eluting Stent Implantation: The — View Citation

* Note: There are 21 references in all — Click here to view all references

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 12 months after randomization according to the ARC definitions.	12 months
Secondary	Patient-oriented composite outcome (POCO)	POCO at 24 and 60 months after randomization according to the ARC consensus	24, 60 months
Secondary	Target vessel failure	Target vessel failure (a composite of cardiac death, target-vessel MI, or target vessel revascularization)	12, 24 and 60 months
Secondary	Cost-effectiveness analysis	Cost-effectiveness analysis	12, 24 and 60 months
Secondary	All-cause and cardiac death	All-cause and cardiac death	12, 24 and 60 months
Secondary	Any nonfatal MI without peri-procedural MI	Any nonfatal MI without peri-procedural MI	12, 24 and 60 months
Secondary	Any nonfatal MI with peri-procedural MI	Any nonfatal MI with peri-procedural MI	12, 24 and 60 months
Secondary	Any target vessel/lesion revascularization	Any target vessel/lesion revascularization	12, 24 and 60 months
Secondary	Any non-target vessel/lesion revascularization	Any non-target vessel/lesion revascularization	12, 24 and 60 months
Secondary	Any revascularization (ischemia-driven or all)	Any revascularization (ischemia-driven or all)	12, 24 and 60 months
Secondary	Stent thrombosis (definite/probable/possible)	Stent thrombosis (definite/probable/possible)	12, 24 and 60 months
Secondary	Stroke (ischemic and hemorrhagic)	Stroke (ischemic and hemorrhagic)	12, 24 and 60 months
Secondary	Acute success of procedure and rate of PCI optimization	Acute success of procedure and rate of PCI optimization	At discharge (1 week after index procedure)