AzTrials
AzTrials

Coronary Artery DiseaseFLAVOUR IIINCT06218485

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

A study testing Intravascular ultrasound-guided stent implantation after angiography-derived FFR-based decision-making and Fractional flow reserve-guided PCI strategy in people with Coronary Artery Disease, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 32 sites in 2 countries.

Active, not recruiting

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

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 19 years and older
Conditions the study is for
Coronary Artery Disease
What is being tested?
Intravascular ultrasound-guided stent implantation after angiography-derived FFR-based decision-making and Fractional flow reserve-guided PCI strategy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,942 participants
Where
32 sitesin 2 countries
Study dates
13 Mar 2024to 1 Sep 2031
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 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 10Show fewer
  • 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).

Trial locations and contacts

32 sites in 2 countries.

32 sites in 2 countries

China25 sites

  • Peking University Third Hospital

    Beijing

  • Xiangya Hospital of Central South University

    Changsha

  • The Southwest Hospital of Army Medical University

    Chongqing

  • Ganzhou People's Hospital

    Ganzhou

  • Second Affiliated Hospital of Shantou University Medical College

    Guangdong

  • Hangzhou First People's Hospital

    Hangzhou

  • Sir Run Run Shaw Hospital

    Hangzhou

  • The Affiliated Hospital of Hangzhou Normal University

    Hangzhou

  • The Second Affiliated Hospital of Zhejiang University School of Medicine

    Hangzhou

  • Zhejiang Hospital

    Hangzhou

  • Changxing People's Hospital

    Huzhou

  • Huzhou Central Hospital

    Huzhou

  • The Fourth People's Hospital of Jinan

    Jinan

  • Jinhua Central Hospital

    Jinhua

  • Jining No.1 People's Hospital

    Jining

  • The First Affiliated Hospital of Nanchang University

    Nanchang

  • The Second Affiliated Hospital of Nanchang University

    Nanchang

  • The First Affiliated Hospital of Guangxi Medical University

    Nanning

  • Ningbo Medical Center Lihuili Hospital

    Ningbo

  • The Affiliated Hospital of Medical College, Ningbo University

    Ningbo

  • Shanxi Cardiovascular Hospital

    Taiyuan

  • The First Affiliated hospital of Wenzhou Medical University

    Wenzhou

  • Renmin Hospital of Wuhan University

    Wuhan

  • Wuhan Aisa Heart Hospital

    Wuhan

  • The Fifth Affiliated Hospital, Sun Yat-sen University

    Zhuhai

Other trials in China

South Korea7 sites

  • Inje University Haeundae Paik Hospital

    Busan

  • Keimyung University Dongsan Medical Center

    Daegu

  • Chonnam National University Hospital

    Donggu

  • Inje University Ilsan Paik Hospital

    Goyang

  • Seoul National University Hospital,

    Seoul

  • Uijeongbu Eulji Medical Center

    Uijeongbu-si

  • Ulsan University Hospital

    Ulsan

Other trials in South Korea

About this study

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)

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.

Read the 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.

Being tested
Intravascular ultrasound-guided stent implantation after angiography-derived FFR-based decision-making, Fractional flow reserve-guided PCI strategy
Keywords
Angiography-derived fractional flow reserve, Intravascular ultrasound, Fractional flow reserve, Percutaneous coronary intervention
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.

  • Intravascular ultrasound-guided stent implantation after angiography-derived FFR-based decision-makingProcedure or surgery

    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 area

  • Fractional flow reserve-guided PCI strategyProcedure or surgery

    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
Study groups in NCT06218485
Study groupRoleWhat they receive
Experimental groupExperimentalThe percutaneous coronary intervention will be performed by intravascular ultrasound (IVUS)-guided strategy after angiography-derived FFR-based decision-making.
Receives: Procedure: Intravascular ultrasound-guided stent implantation after angiography-derived FFR-based decision-making
Control groupActive comparatorThe percutaneous coronary intervention will be performed by fractional flow reserve (FFR)-guided strategy.
Receives: Procedure: Fractional flow reserve-guided PCI strategy

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 24 months after randomization.

    Measured: 24 months

Secondary outcomes (11)

  1. 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.

    Measured: 60 months

  2. Individual component of Patient-oriented composite outcome

    Individual component of Patient-oriented composite outcome (death, myocardial infarction, revascularization).

    Measured: 24 and 60 months

  3. Target vessel failure

    Target vessel failure, defined as a composite of cardiac death, target-vessel MI, or target vessel revascularization.

    Measured: 24 and 60 months

  4. All-cause and cardiac death

    All-cause and cardiac death.

    Measured: 24 and 60 months

  5. Any nonfatal myocardial infarction without peri-procedural myocardial infarction

    Any nonfatal myocardial infarction without peri-procedural myocardial infarction.

    Measured: 24 and 60 months

  6. Any nonfatal myocardial infarction with peri-procedural myocardial infarction

    Any nonfatal myocardial infarction with peri-procedural myocardial infarction.

    Measured: 24 and 60 months

  7. Any target vessel/lesion revascularization

    Any target vessel/lesion revascularization.

    Measured: 24 and 60 months

  8. Any non-target vessel/lesion revascularization

    Any non-target vessel/lesion revascularization.

    Measured: 24 and 60 months

  9. Any revascularization (ischemia-driven or all)

    Any revascularization (ischemia-driven or all).

    Measured: 24 and 60 months

  10. Stent thrombosis (definite/probable/possible)

    Stent thrombosis at 24 and 60 months after randomization.

    Measured: 24 and 60 months

  11. Stroke (ischemic and hemorrhagic)

    Stroke at 24 and 60 months after randomization.

    Measured: 24 and 60 months

Timeline

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

  1. First posted23 Jan 2024
  2. Study start13 Mar 2024
  3. Primary completion1 Sep 2028 (estimated)
  4. Study completion1 Sep 2031 (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
1,942 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06218485
Sponsor's protocol ID
2023-0896
Acronym
FLAVOUR III
Status last verified
Aug 2026
First submitted
27 Nov 2023
Last updated
27 Aug 2026
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 study completion.

Publications

  • 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.

    PubMed 29790954

  • 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.

    PubMed 32295416

  • 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.

    PubMed 35435570

  • 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

  • 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

  • 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

  • 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.

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

    PubMed 28317438

  • 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 Decision Making. JACC Cardiovasc Interv. 2020 Jul 27;13(14):1617-1638. doi: 10.1016/j.jcin.2020.04.040.

    PubMed 32703589

  • 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 SV, Sellke FW, Sharma G, Yong CM, Zwischenberger BA. 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022 Jan 18;79(2):e21-e129. doi: 10.1016/j.jacc.2021.09.006. Epub 2021 Dec 9.

    PubMed 34895950

Questions about this trial

What is this clinical trial studying?

A study testing Intravascular ultrasound-guided stent implantation after angiography-derived FFR-based decision-making and Fractional flow reserve-guided PCI strategy in people with Coronary Artery Disease, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 32 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 5 inclusion and 10 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 27 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 32 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: 24 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 NCT06218485, which also lists 10 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 27 Aug 2026; AzTrials last refreshed its copy on 7 Nov 2026.

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