Clinical trial NCT02673424: Fractional FLow Reserve And IVUS for Clinical OUtcomes in Patients With InteRmediate Stenosis
Official title: Comparison of Clinical Outcomes Between Imaging and Physiology-guided Intervention Strategy in Patients With Intermediate Stenosis: Fractional FLow Reserve And IVUS for Clinical OUtcomes in Patients With InteRmediate Stenosis (FLAVOUR)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Stable Angina
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
Collaborators: name: Second Affiliated Hospital, School of Medicine, Zhejiang University
name: Samsung Medical Center, Sungkyunkwan University School of Medicine
name: Ulsan University Hospital
name: Keimyung University Dongsan Medical Center
name: Inje University
name: KangWon National University Hospital
name: Ajou University School of Medicine
First posted: 2016-02-03
Enrollment: 1700
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To compare the safety and efficacy of FFR (fractional flow reserve)-guided percutaneous coronary intervention (PCI) strategy with IVUS (intravascular ultrasound \[IVUS\])-guided PCI in patients with intermediate coronary stenosis.

Detailed description: 1. Study overview This study is a prospective, open-label, randomized, multicenter trial to test the safety and efficacy of physiology- or imaging-guided PCI in patients with intermediate coronary stenosis.

   The primary hypothesis is that FFR-guided strategy will show non-inferior rate of patients-oriented composite outcomes (POCO) at 24 months after randomization, compared with IVUS-guided strategy in patients with intermediate coronary stenosis.
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 24 months after PCI will be 10% in the FFR-guided arm, and 12% in the IVUS-guided arm.
   * Primary endpoint: patient-oriented composite outcome (a composite of all-cause death, MI, any repeat revascularization) at 24 months after PCI
   * Design: non-inferiority , delta = 2.5%
   * Sampling ratio: FFR-guided strategy : IVUS-guided strategy = 1:1
   * Type I error (α): One-sided 5%
   * Accrual time : 2 years
   * Total time : 4 years (accrual 2 year + follow-up 2 years)
   * Assumption: POCO 10.0% vs. 12.0% in FFR or IVUS-guided strategy, respectively
   * Statistical power (1- β): 90%
   * Primary statistical method : Kaplan-Meier survival analysis with log-rank test
   * Potential withdrawal rates : total 2%
   * Stratification in Randomization: Presence of Diabetes Mellitus (600 patients (35%) will be Diabetic patients, with 300 patients in each group)

   Based on the above assumption, 1,700 patients (850 patients in each group) will be enrolled in this study with consideration of withdrawal rates.
3. Research Materials and Indication for Revascularization For the FFR-guided strategy arm, a pressure-sensor wire system will be used and the criterion for revascularization is FFR ≤ 0.80. Hyperemia will be induced by intravenous infusion of adenosine (140ug/kg/min). For the IVUS-guided strategy arm, the criterion for revascularization is MLA ≤ 3mm2 or \[3mm2 \< MLA ≤ 4mm2 and plaque burden \> 70%\].
4. Funding This is an investigator-initiated study with grant support from Boston Scientific. Other than financial sponsorship, the company has no role in protocol development or the implementation, management, data collection, and analysis of this study.
5. Extended Outcome Follow-Up Following the 2-year follow-up period, clinical outcomes will also be collected until September 30, 2024, to assess the long-term outcomes of each treatment group.

Eligibility criteria: 1. Inclusion Criteria

   * Subject must be ≥ 19 years ② Subject is able to verbally confirm understandings of risks, benefits and treatment alternatives of receiving invasive physiologic or imaging evaluation and PCI 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 ④ Patients with intermediate degree of stenosis (40-70% stenosis by visual estimation) eligible for stent implantation who need FFR or IVUS for further evaluation ⑤ Target vessel size \> 2.5mm

       * Target lesions located at the proximal to mid part of coronary artery
2. Exclusion Criteria

   * Known hypersensitivity or contraindication to any of the following medications: Heparin, Aspirin, Clopidogrel, Prasugrel, Ticagrelor, Adenosine.

     * Active pathologic bleeding

       * Gastrointestinal or genitourinary major bleeding within the prior 3 months.

         * History of bleeding diathesis, known coagulopathy (including heparin-induced thrombocytopenia) ⑤ Non-cardiac co-morbid conditions with life expectancy \< 2 years ⑥ Target lesion located in coronary arterial bypass graft ⑦ Target lesion located in the left main coronary artery

Primary outcomes:
measure: Patient-oriented composite outcome
timeFrame: 24 months
measure: Long-term patient-oriented composite outcome
timeFrame: Up to 7 years
Secondary outcomes:
measure: Patient-oriented composite outcome
timeFrame: 12 months
measure: Stent-oriented composite endpoint
timeFrame: 12 months
measure: Stent-oriented composite endpoint
timeFrame: 24 months
measure: Cost-effectiveness analysis
timeFrame: 24 months
measure: All-cause death
timeFrame: 24 months
measure: Cardiac death
timeFrame: 24 months
measure: Target-vessel and all-cause nonfatal myocardial infarction without per-procedural myocardial infarction
timeFrame: 24 months
measure: Target-vessel and all-cause nonfatal myocardial infarction with per-procedural myocardial infarction
timeFrame: 24 months
measure: Peri-procedural MI using referred definitions
timeFrame: At discharge (1 week after index procedure)
measure: Target vessel/lesion revascularization
timeFrame: 24 months
measure: Non-target vessel/lesion revascularization
timeFrame: 24 months
measure: Any revascularization
timeFrame: 24 months
measure: Academic Research Consortium defined - Stent thrombosis
timeFrame: 24 months
measure: Stroke
timeFrame: 24 months
measure: Acute success of procedure
timeFrame: immediately after the intervention
measure: Angina severity measured with Seattle Angina Questionnaires
timeFrame: 12 months
measure: Angina severity measured with Seattle Angina Questionnaires
timeFrame: 24 months
measure: Long-term patient-oriented composite outcome in subgroups by use of anti-platelet agent and lipid-lowering agents
timeFrame: Up to 7 years
measure: Long-term patient-oriented composite outcome in subgroups by lipid profiles
timeFrame: Up to 7 years
measure: Long-term mortality
timeFrame: Up to 7 years
measure: Long-term myocardial infarction
timeFrame: Up to 7 years
measure: Long-term any revascularization
timeFrame: Up to 7 years
measure: Long-term target vessel failure
timeFrame: Up to 7 years
measure: Long-term target vessel myocardial infarction
timeFrame: Up to 7 years
measure: Long-term target vessel revascularization
timeFrame: Up to 7 years
measure: Long-term target lesion revascularization
timeFrame: Up to 7 years
measure: Long-term non-target lesion revascularization-target vessel revascularization
timeFrame: Up to 7 years
measure: Long-term stent thrombosis
timeFrame: Up to 7 years
measure: Long-term stroke
timeFrame: Up to 7 years
measure: Landmark analysis for patient-oriented composite outcome
timeFrame: Up to 7 years
measure: Long-term patient-oriented composite outcome in the medical treatment group
timeFrame: Up to 7 years
measure: Long-term patient-oriented composite outcome in the PCI group
timeFrame: Up to 7 years
measure: Long-term patient-oriented composite outcome according to PCI optimization
timeFrame: Up to 7 years
measure: Landmark analysis for target vessel failure
timeFrame: Up to 7 years
measure: Long-term target vessel failure in the medical treatment group
timeFrame: Up to 7 years
measure: Long-term target vessel failure in the PCI group
timeFrame: Up to 7 years
measure: Long-term target vessel failure according to PCI optimization
timeFrame: Up to 7 years
measure: Long-term target vessel failure according to IVUS-derived plaque characteristics
timeFrame: Up to 7 years
measure: Long-term target vessel failure according to QFR values
timeFrame: Up to 7 years
Other outcomes:
Locations:
city: Zhejiang
country: China
facility: The Second Affiliated Hospital, School of Medicine, Zhejiang University
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Goyang
country: Korea, Republic of
facility: Inje University Ilsan Paik Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center, Sungkyunkwan University School of Medicine
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital, Seoul, Korea
Study officials:
affiliation: Seoul National University Hospital
name: Bon-Kwon Koo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ajou University School of Medicine
name: Seung-Jea Tahk, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Second Affiliated Hospital, School of Medicine, Zhejiang University
name: JianAn Wang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.