Stable Angina
Conditions
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.
Interventions
PROCEDUREFFR-guided stenting
The percutaneous coronaryintervention using drug-eluting stent will be indicated according to following criteria in the FFR-guided strategy arm \* Criteria for revascularization: The FFR ≤ 0.80 will be targeted for PCI
PROCEDUREIVUS-guided stenting
The percutaneous coronaryintervention 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 (MLA ≤ 4mm2 AND Plaque burden \>70%)
Sponsors
Second Affiliated Hospital, School of Medicine, Zhejiang University
Samsung Medical Center, Sungkyunkwan University School of Medicine
Ulsan University Hospital
Keimyung University Dongsan Medical Center
Inje University
KangWon National University Hospital
Ajou University School of Medicine
Seoul National University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patient-oriented composite outcome | 24 months | a composite of all death, myocardial infarction (MI) or any revascularization |
| Long-term patient-oriented composite outcome | Up to 7 years | A composite of all death, myocardial infarction \[MI, including peri-procedural MI\] or any revascularization during the extended follow-up period after randomization according to the ARC consensus. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cost-effectiveness analysis | 24 months | medical expenses of treatment and follow-up. Cost estimates utilize micro-costing, the total cost by identifying the utilization of medical resources used, and macro-costing, medical expenses resulting from clinical events from health insurance data. |
| All-cause death | 24 months | death from any cause |
| Cardiac death | 24 months | death from cardiaccause |
| Target-vessel and all-cause nonfatal myocardial infarction without per-procedural myocardial infarction | 24 months | Myocardial infarction during 24 months follow-up without periprocedural myocardial infarction |
| Target-vessel and all-cause nonfatal myocardial infarction with per-procedural myocardial infarction | 24 months | Myocardial infarction during 24 months follow-up with periprocedural myocardial infarction |
| Peri-procedural MI using referred definitions | At discharge (1 week after index procedure) | Number of participants with peri-procedural myocardial infarction after PCI |
| Target vessel/lesion revascularization | 24 months | Number of participants and vessels/lesions with ischemia-driven or any reavascularizations at target vessel/lesion |
| Non-target vessel/lesion revascularization | 24 months | Number of participants and vessels/lesions with ischemia-driven or any reavascularizations at non-target vessel/lesion. |
| Any revascularization | 24 months | Number of participants and vessels/lesions with ischemia-driven or any revascularizations at any vessel/lesion |
| Academic Research Consortium defined - Stent thrombosis | 24 months | Number of participants with definite/probable/possible stent thrombosis |
| Stroke | 24 months | Number of participants with ischemic or hemorrhagic stroke |
| Acute success of procedure | immediately after the intervention | Device-related, lesion-related and procedure-related success of index procedure (residual diameter stenosis\<50% and thrombolysis in myocardial infarction flow 3) |
| Angina severity measured with Seattle Angina Questionnaires | 12 months | Seattle Angina Questionnaires (physical limitation and angina frequency were classified as minimal: 75-100, mild: 50-74, moderate: 25-49, severe: 0-24) |
| Long-term patient-oriented composite outcome in subgroups by use of anti-platelet agent and lipid-lowering agents | Up to 7 years | A composite of all death, myocardial infarction \[MI, including peri-procedural MI\] or any revascularization during the extended follow-up period in subgroups stratified by use of anti-platelet agent and lipid-lowering agents |
| Long-term patient-oriented composite outcome in subgroups by lipid profiles | Up to 7 years | Long-term patient-oriented composite outcome in subgroups stratified by changes in LDL-cholesterol, HDL-cholesterol, and triglyceride during the extended follow-up period |
| Long-term mortality | Up to 7 years | All-cause and cardiac death during the extended follow-up period |
| Long-term myocardial infarction | Up to 7 years | Myocardial infarction during the extended follow-up period |
| Patient-oriented composite outcome | 12 months | a composite of all death, myocardial infarction (MI) or any |
| Long-term target vessel failure | Up to 7 years | Target vessel failure (cardiac death, target vessel MI, target vessel revascularization) during the extended follow-up period |
| Long-term target vessel myocardial infarction | Up to 7 years | Target vessel myocardial infarction during the extended follow-up period |
| Long-term target vessel revascularization | Up to 7 years | Target vessel revascularization during the extended follow-up period |
| Long-term target lesion revascularization | Up to 7 years | Target lesion revascularization during the extended follow-up period |
| Long-term non-target lesion revascularization-target vessel revascularization | Up to 7 years | Non-target lesion revascularization-target vessel revascularization during the extended follow-up period |
| Long-term stent thrombosis | Up to 7 years | Stent thrombosis (definite/probable/possible) during the extended follow-up period |
| Long-term stroke | Up to 7 years | Stroke (ischemic and hemorrhagic) during the extended follow-up period |
| Landmark analysis for patient-oriented composite outcome | Up to 7 years | A 2 year landmark analysis of patient-oriented composite outcome and its individual outcome components |
| Long-term patient-oriented composite outcome in the medical treatment group | Up to 7 years | Patient-oriented composite outcome and individual components of outcomes in the medical treatment group |
| Long-term patient-oriented composite outcome in the PCI group | Up to 7 years | Patient-oriented composite outcome and individual components of outcomes in the PCI group |
| Long-term patient-oriented composite outcome according to PCI optimization | Up to 7 years | Patient-oriented composite outcome and individual outcome components among patients in the PCI group, comparing those who received PCI optimization to those who did not. |
| Landmark analysis for target vessel failure | Up to 7 years | A 2 year landmark analysis of target vessel failure and its individual outcome components |
| Long-term target vessel failure in the medical treatment group | Up to 7 years | Target vessel failure and individual components of outcomes in the medical treatment group |
| Long-term target vessel failure in the PCI group | Up to 7 years | Target vessel failure and individual components of outcomes in the PCI group |
| Long-term target vessel failure according to PCI optimization | Up to 7 years | Target vessel failure and individual outcome components among patients in the PCI group, comparing those who received PCI optimization to those who did not. |
| Long-term target vessel failure according to IVUS-derived plaque characteristics | Up to 7 years | Target vessel failure (cardiac death, target vessel MI, target vessel revascularization) during the extended follow-up period according to IVUS-derived plaque characteristics |
| Long-term target vessel failure according to QFR values | Up to 7 years | Target vessel failure (cardiac death, target vessel MI, target vessel revascularization) during the extended follow-up period according to QFR values |
| Long-term any revascularization | Up to 7 years | Any revascularization during the extended follow-up period |
| Stent-oriented composite endpoint | 12 months | a composite of cardiac death, target-vessel MI, or target lesion revascularization |
Countries
China, South Korea
Outcome results
None listed