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Coronary Artery DiseaseFLAVOUR IINCT04397211

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

A study testing Angiography-derived FFR and IVUS in people with Coronary Artery Disease, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 23 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
Coronary Artery Disease
What is being tested?
Angiography-derived FFR and IVUS
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,872 participants
Where
23 sitesin 2 countries
Study dates
29 May 2020to Sep 2028
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ① Subject must be ≥ 18 years. ② 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. ③ Patients suspected with ischemic heart disease. ④ Patients with ≥ 50% stenosis by angiography-based visual estimation eligible for stent implantation. ⑤ Target vessel size ≥ 2.5mm in visual estimation. ⑥ Target vessels are limited to major epicardial coronary arteries (left anterior descending artery[LAD], left circumflex artery [LCX], right coronary artery [RCA])

Who cannot join

  • ① 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.) ② Patients with active pathologic bleeding. ③ Gastrointestinal or genitourinary major bleeding within the prior 3 months. ④ History of bleeding. diathesis, known coagulopathy (including heparin-induced thrombocytopenia). ⑤Non-cardiac co-morbid conditions with life expectancy < 1 year. ⑥ Target vessel total occlusion. ⑦ Target lesion located in coronary arterial bypass graft. ⑧ Left main coronary artery stenosis ≥ 50%. ⑨ Not eligible for angiography-derived FFR (ostial RCA ≥ 50% stenosis, myocardial bridging, severe tortuosity, severe overlap, poor image quality)

Trial locations and contacts

23 sites in 2 countries.

23 sites in 2 countries

China21 sites

  • Peking University Third Hospital

    Beijing

  • Second Affiliated Hospital of Shantou University Medical College

    Guangdong

  • Second Affiliated Hospital, School of Medicine, Zhejiang University, China

    Hangzhou, Zhejiang

  • Affiliated Hangzhou First People's Hospital

    Hangzhou

  • The Affiliated Hospital of Hangzhou Normal University

    Hangzhou

  • Zhejiang Greentown Cardiovascular Hospital

    Hangzhou

  • Changxing People's Hospital

    Huzhou

  • Huzhou Central Hospital

    Huzhou

  • The Fourth People's Hospital of Jinan

    Jinan

  • Dongyang People's Hospital

    Jinhua

  • Jinhua Central Hospital

    Jinhua

  • First Affiliated Hospital of Kunming Medical University

    Kunming

  • The First Affiliated Hospital of Nanchang University

    Nanchang

  • The Affiliated Hospital of Medical College, Ningbo University

    Ningbo

  • Shandong Jining No.1 People's Hospital

    Shandong

  • Shandong University of Traditional Chinese Medicine

    Shandong

  • Renji Hospital Shanghai Jiaotong University School of Medicine

    Shanghai

  • Second hospital of Shanxi Medical University

    Taiyuan

  • The first affiliated hospital of Wenzhou Medical University

    Wenzhou

  • The second affiliated hospital of Wenzhou Medical University

    Wenzhou

  • Zhongnan Hospital of Wuhan University

    Wuhan

Other trials in China

South Korea2 sites

  • Seoul National University Hospital,

    Seoul

  • Ulsan University Hospital

    Ulsan

Other trials in South Korea

About this study

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

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

Read the detailed 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.
  1. 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%].
Being tested
Angiography-derived FFR, IVUS
Keywords
Angiography-derived fractional flow reserve, Intravascular ultrasound, Percutaneous coronary intervention, Fractional flow reserve
Medical subject headings
Coronary Artery Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Angiography-derived FFRProcedure or surgery

    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

  • IVUSProcedure or surgery

    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%

Study groups in NCT04397211
Study groupRoleWhat they receive
Angiography-derived FFR-guided PCI groupActive comparatorPercutaneous coronary intervention using drug-eluting stent(s) will be performed by Angiography-derived FFR-guided strategy
Receives: Procedure: Angiography-derived FFR
IVUS-guided PCI groupActive comparatorPercutaneous coronary intervention using drug-eluting stent(s) will be performed by IVUS-guided strategy
Receives: Procedure: IVUS

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 12 months

Secondary outcomes (12)

  1. Patient-oriented composite outcome (POCO)

    POCO at 24 and 60 months after randomization according to the ARC consensus

    Measured: 24, 60 months

  2. Target vessel failure

    Target vessel failure (a composite of cardiac death, target-vessel MI, or target vessel revascularization)

    Measured: 12, 24 and 60 months

  3. Cost-effectiveness analysis

    Cost-effectiveness analysis

    Measured: 12, 24 and 60 months

  4. All-cause and cardiac death

    All-cause and cardiac death

    Measured: 12, 24 and 60 months

  5. Any nonfatal MI without peri-procedural MI

    Any nonfatal MI without peri-procedural MI

    Measured: 12, 24 and 60 months

  6. Any nonfatal MI with peri-procedural MI

    Any nonfatal MI with peri-procedural MI

    Measured: 12, 24 and 60 months

  7. Any target vessel/lesion revascularization

    Any target vessel/lesion revascularization

    Measured: 12, 24 and 60 months

  8. Any non-target vessel/lesion revascularization

    Any non-target vessel/lesion revascularization

    Measured: 12, 24 and 60 months

  9. Any revascularization (ischemia-driven or all)

    Any revascularization (ischemia-driven or all)

    Measured: 12, 24 and 60 months

  10. Stent thrombosis (definite/probable/possible)

    Stent thrombosis (definite/probable/possible)

    Measured: 12, 24 and 60 months

  11. Stroke (ischemic and hemorrhagic)

    Stroke (ischemic and hemorrhagic)

    Measured: 12, 24 and 60 months

  12. Acute success of procedure and rate of PCI optimization

    Acute success of procedure and rate of PCI optimization

    Measured: At discharge (1 week after index procedure)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 May 2020
  2. Study start29 May 2020
  3. Primary completionSep 2024 (estimated)
  4. Study completionSep 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Parallel Assignment
Masking
None (open label)
Enrolment
1,872 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04397211
Sponsor's protocol ID
2019-303
Acronym
FLAVOUR II
Status last verified
Jan 2024
First submitted
17 May 2020
Last updated
23 Jan 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: The deidentified data will be shared after publication of first manuscript

Publications

  • 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 Heart Association Task Force on Practice Guidelines; Society for Cardiovascular Angiography and Interventions. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011 Dec 6;58(24):e44-122. doi: 10.1016/j.jacc.2011.08.007. Epub 2011 Nov 7. No abstract available.

    PubMed 22070834

  • 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; FAME 2 Trial Investigators. Fractional flow reserve-guided PCI for stable coronary artery disease. N Engl J Med. 2014 Sep 25;371(13):1208-17. doi: 10.1056/NEJMoa1408758. Epub 2014 Sep 1.

    PubMed 25176289

  • 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. JACC Cardiovasc Interv. 2010 Mar;3(3):307-14. doi: 10.1016/j.jcin.2009.12.010.

    PubMed 20298990

  • 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 Cardiol. 2007 May 29;49(21):2105-11. doi: 10.1016/j.jacc.2007.01.087. Epub 2007 May 17.

    PubMed 17531660

  • 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 individual patient-data meta-analysis. Catheter Cardiovasc Interv. 2019 Nov 1;94(5):693-701. doi: 10.1002/ccd.28283. Epub 2019 Apr 9.

    PubMed 30963676

  • 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.

    PubMed 30586699

  • 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, Christiansen EH, Holm NR. Evaluation of Coronary Artery Stenosis by Quantitative Flow Ratio During Invasive Coronary Angiography: The WIFI II Study (Wire-Free Functional Imaging II). Circ Cardiovasc Imaging. 2018 Mar;11(3):e007107. doi: 10.1161/CIRCIMAGING.117.007107.

    PubMed 29555835

  • 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, Ronco F, Botker HE, Wijns W, Christiansen EH, Holm NR. Diagnostic Performance of In-Procedure Angiography-Derived Quantitative Flow Reserve Compared to Pressure-Derived Fractional Flow Reserve: The FAVOR II Europe-Japan Study. J Am Heart Assoc. 2018 Jul 6;7(14):e009603. doi: 10.1161/JAHA.118.009603.

    PubMed 29980523

  • 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.

    PubMed 30137305

  • 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.

    PubMed 29101020

  • 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 Derive Fractional Flow Reserve From Diagnostic Coronary Angiography: The International Multicenter FAVOR Pilot Study. JACC Cardiovasc Interv. 2016 Oct 10;9(19):2024-2035. doi: 10.1016/j.jcin.2016.07.013.

    PubMed 27712739

  • 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-eluting stent implantation: an intravascular ultrasound study. J Am Coll Cardiol. 2005 Apr 5;45(7):995-8. doi: 10.1016/j.jacc.2004.12.066.

    PubMed 15808753

  • 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 in three randomized trials and 14 observational studies. Am J Cardiol. 2014 Apr 15;113(8):1338-47. doi: 10.1016/j.amjcard.2013.12.043. Epub 2014 Jan 31.

    PubMed 24685326

  • 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-guided. JACC Cardiovasc Interv. 2010 Aug;3(8):812-7. doi: 10.1016/j.jcin.2010.04.016.

    PubMed 20723852

  • 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 H, Takashima H, Kikuta Y, Erglis A, Vinhas H, Canas Silva P, Baptista SB, Alghamdi A, Hellig F, Koo BK, Nam CW, Shin ES, Doh JH, Brugaletta S, Alegria-Barrero E, Meuwissen M, Piek JJ, van Royen N, Sezer M, Di Mario C, Gerber RT, Malik IS, Sharp ASP, Talwar S, Tang K, Samady H, Altman J, Seto AH, Singh J, Jeremias A, Matsuo H, Kharbanda RK, Patel MR, Serruys P, Escaned J. Use of the Instantaneous Wave-free Ratio or Fractional Flow Reserve in PCI. N Engl J Med. 2017 May 11;376(19):1824-1834. doi: 10.1056/NEJMoa1700445. Epub 2017 Mar 18.

    PubMed 28317458

Questions about this trial

What is this clinical trial studying?

A study testing Angiography-derived FFR and IVUS in people with Coronary Artery Disease, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 23 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 23 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in China, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Patient-oriented composite outcome (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04397211, which also lists 24 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2024.

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