FFR Versus IVUS with Angiography-Derived FFR for Clinical Outcomes in Patients with Coronary Artery Disease (FLAVOUR III)

February 20, 2025 updated by: Second Affiliated Hospital, School of Medicine, Zhejiang University

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

1942

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Xinyang Hu, MD, PhD
  • Phone Number: +86 0571 87784808
  • Email: hxy0507@126.com

Study Contact Backup

Study Locations

  • China
      • Beijing, China
        • Recruiting
        • Peking University Third Hospital
        • Contact:
      • Guangdong, China
        • Recruiting
        • Second Affiliated Hospital of Shantou University Medical College
        • Contact:
          • Jilin Li, MD
      • Hangzhou, China
        • Not yet recruiting
        • The Second Affiliated Hospital of Zhejiang University School of Medicine
        • Contact:
          • Xinyang Hu, MD, PhD
      • Hangzhou, China
        • Recruiting
        • The affiliated hospital of Hangzhou Normal University
        • Contact:
      • Huzhou, China
        • Recruiting
        • Changxing People's Hospital
        • Contact:
          • Dongsheng Lu, MD
      • Jinan, China
        • Recruiting
        • The Fourth People's Hospital of Jinan
        • Contact:
          • Qiang Liu, MD
      • Jinan, China
        • Not yet recruiting
        • The Affiliated Hospital of Shandong University of TCM
        • Contact:
          • Jianliang Ma, MD
      • Jinhua, China
        • Recruiting
        • Jinhua Central Hospital
        • Contact:
          • Yibin Pan, MD
      • Kunming, China
        • Not yet recruiting
        • First Affiliated Hospital of Kunming Medical University
        • Contact:
      • Nanchang, China
        • Recruiting
        • The First Affiliated Hospital of Nanchang University
        • Contact:
          • Xiaoping Peng, MD
      • Ningbo, China
        • Recruiting
        • The Affiliated Hospital of Medical College, Ningbo University
        • Contact:
          • Wenming He, MD
      • Ningbo, China
        • Not yet recruiting
        • Ningbo Medical Center Lihuili Hospital
        • Contact:
          • Wanying Hu, MD
      • Shanghai, China
        • Not yet recruiting
        • Renji Hospital Shanghai Jiaotong University School of Medicine
        • Contact:
      • Wenzhou, China
        • Recruiting
        • The First Affiliated Hospital of Wenzhou Medical University
        • Contact:
          • Hao Zhou
  • Korea, Republic of
      • Bucheon, Korea, Republic of
        • Not yet recruiting
        • Bucheon Sejong Hospital
        • Contact:
          • Hyun-Jong Lee, MD, PhD
      • Busan, Korea, Republic of
        • Not yet recruiting
        • Inje University Haeundae Paik Hospital
        • Contact:
          • Dong-Kie Kim, MD, PhD
      • Daegu, Korea, Republic of
        • Not yet recruiting
        • Keimyung University Dongsan Medical Center
        • Contact:
          • Chang-Wook Nam, MD, PhD
      • Daegu, Korea, Republic of
        • Not yet recruiting
        • Kyungpook National University Hospital
        • Contact:
          • Jang Hoon Lee, MD, PhD
      • Donggu, Korea, Republic of
        • Not yet recruiting
        • Chonnam National University Hospital
        • Contact:
          • Young Joon Hong, MD, PhD
      • Goyang, Korea, Republic of
        • Not yet recruiting
        • Inje University Ilsan Paik Hospital
        • Contact:
          • Joon-Hyung Doh, MD, PhD
      • Seoul, Korea, Republic of
        • Recruiting
        • Seoul National University Hospital,
        • Contact:
      • Seoul, Korea, Republic of
        • Not yet recruiting
        • Seoul St. Mary'S Hospital
        • Contact:
          • Kwan Yong Lee, MD, PhD
      • Uijeongbu, Korea, Republic of
        • Not yet recruiting
        • Uijeongbu Eulji Medical Center
        • Contact:
          • You-Jeong Ki, MD, PhD
      • Ulsan, Korea, Republic of
        • Not yet recruiting
        • Ulsan University Hospital
        • Contact:
          • Eun-seok Shin, MD
      • Wonju, Korea, Republic of
        • Not yet recruiting
        • Yonsei University Wonju Severance Hospital
        • Contact:
          • Sung Gyun Ahn, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental group
The percutaneous coronary intervention will be performed by intravascular ultrasound (IVUS)-guided strategy after angiography-derived FFR-based decision-making.
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:

  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
Active Comparator: Control group
The percutaneous coronary intervention will be performed by fractional flow reserve (FFR)-guided strategy.
Procedure: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patient-oriented composite outcome
Time Frame: 24 months
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 Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University

Collaborators

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

Investigators

  • Principal Investigator: Jian'an Wang, MD, PhD, Second Affiliated Hospital, School of Medicine, Zhejiang University
  • Principal Investigator: Bon-Kwon Koo, MD, PhD, Seoul National University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 13, 2024

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2029

Study Registration Dates

First Submitted

November 27, 2023

First Submitted That Met QC Criteria

January 21, 2024

First Posted (Actual)

January 23, 2024

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 20, 2025

Last Verified

September 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023-0896

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The deidentified data will be shared after publication of first manuscript

IPD Sharing Time Frame

Data will be available within 12 months of study completion.

IPD Sharing Access Criteria

Data access requests will be reviewed by an external Independent Review Panel. Requestors will be required to sign a Data Access Agreement

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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