Intravascular Imaging- Versus Angiography-Guided Percutaneous Coronary Intervention For Complex Coronary Artery Disease

Study Overview
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Brief Summary
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The aim of the study is to compare clinical outcomes between intravascular imaging-guided versus angiography-guided percutaneous coronary intervention (PCI) in complex lesions.

Detailed Description
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After introduction of the 2nd generation drug-eluting stents (DES), the rates of device-related failure or target lesion failure such as restenosis and stent thrombosis has been markedly decreased, compared with the era of bare metal stents or 1st generation DES. Nevertheless, patients undergoing percutaneous coronary intervention (PCI) for complex lesions, for example, chronic total occlusion (CTO), left main disease, true bifurcation lesion, long lesion, multi-vessel PCI, multiple overlapping stents, or severely calcified lesions have significantly worse clinical outcomes than those with non-complex lesions. During the PCI procedure, intravascular ultrasound (IVUS) and optical coherence tomography (OCT) are useful tools for providing information on preintervention lesion characteristics, including vulnerable plaques, lesion severity, length, and morphology; on postintervention optimal stent implantation for stent expansion, extension, and apposition; and on possible complications after stent implantation. Therefore, intravascular imaging guidance may improve clinical outcomes after complex PCI. However, although previous randomized controlled trial (RCT) and registries showed significantly lower rates of major adverse clinical events following IVUS-guided PCI compared with angiography-guided PCI, the RCTs were limited with small sample size and dealt with very selected lesion subsets such as CTO or long lesion. Moreover, it is uncertain whether OCT-guided PCI improves clinical outcomes compared with angiography-guided PCI. Meanwhile, appropriate imaging modality may differ according to patient and lesion characteristics. One of the ways to maximize the advantage of intravascular imaging is choice of intravascular imaging devices by the operator's discretion. Therefore, the current RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance versus Angiography-Guidance on Clinical Outcomes After Complex Percutaneous Coronary Intervention) is designed to investigate whether PCI under guidance of intravascular imaging devices (IVUS or OCT) chosen by operators would improve clinical outcomes compared with angiography-guided PCI in patients with complex lesions.

Official Title
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Randomized Controlled Trial of Intravascular Imaging Guidance Versus Angiography-Guidance on Clinical Outcomes After Complex Percutaneous Coronary Intervention (RENOVATE-COMPLEX-PCI)

Conditions
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Coronary Artery Disease, Atherosclerosis

Intervention / Treatment
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* Procedure: Percutaneous coronary intervention for complex lesion
* Device: Drug-eluting stent
* Device: Intravascular imaging (IVUS or OCT)
* Device: Drug-coated balloon


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject age ≥19 years old Coronary artery disease requiring PCI Patients with complex lesion True bifurcation lesion (Medina 1,1,1/1,0,1/0,1,1) with side branch ≥2.5mm size Chronic total occlusion (≥3 months) as target lesion Unprotected LM disease PCI (LM ostium, body, distal LM bifurcation including non-true bifurcation) Long coronary lesions (implanted stent ≥38 mm in length) Multi-vessel PCI (≥2 vessels treated at one PCI session) Multiple stents needed (≥3 more stent per patient) In-stent restenosis lesion as target lesion Severely calcified lesion (encircling calcium in angiography) Ostial coronary lesion (LAD, LCX, RCA) Subject is able to verbally confirm understandings of risks, benefits and treatment alternatives of receiving invasive physiologic evaluation and PCI and he/she or his/her legally authorized representative provides written informed consent prior to any study related procedure. Exclusion Criteria: Target lesions not amenable for PCI by operators' decision Cardiogenic shock (Killip class IV) at presentation Intolerance to Aspirin, Clopidogrel, Prasugrel, Ticagrelor, Heparin, or Everolimus Known true anaphylaxis to contrast medium (not allergic reaction but anaphylactic shock) Pregnancy or breast feeding Non-cardiac co-morbid conditions are present with life expectancy <1 year or that may result in protocol non-compliance (per site investigator's medical judgment) Unwillingness or inability to comply with the procedures described in this protocol.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, open label, two-arm, randomized controlled trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intravascular imaging arm<br>The choice of intravascular imaging devices such as IVUS or OCT during PCI will be left to the operator's discretion. In case of staged procedure during the same hospitalization, following the initially allocated strategy would be strongly recommended. Use of intravascular imaging devices will be allowed at any step of PCI (pre-PCI, during PCI and post-PCI), but intravascular imaging evaluation after stent implantation will be mandatory. | Procedure: Percutaneous coronary intervention for complex lesion<br>* In patients who have complex coronary lesions, PCI will performed using intravascular imaging or angiography only according to the allocated arms Intravascular imaging arm Angiography arm Definition of Complex Lesions True bifurcation lesion (Medina 1,1,1/1,0,1/0,1,1) with side branch ≥2.5mm size Chronic total occlusion (≥3 months) as target lesion PCI for unprotected left main (LM) disease (LM os, body, distal LM bifurcation including non-true bifurcation) Implanted stent length ≥38mm Multi-vessel PCI (≥2 major epicardial coronary arteries treated at one PCI session) Multiple stent needed (≥3 more stent per patient) In-stent restenosis lesion as target lesion Severely calcified lesion (encircling calcium in angiography) Ostial coronary lesion (LAD, LCX, RCA)<br>Device: Drug-eluting stent<br>* All patient will be received percutaneous coronary intervention with second generation drug-eluting stent or drug-coated balloon.<br>Device: Intravascular imaging (IVUS or OCT)<br>* IVUS Reference site: Largest lumen, Plaque burden <50% Stent sizing: By measuring vessel diameter (external elastic membrane) at proximal and distal reference sites. The averaged value of the proximal and distal reference external elastic membrane diameter will be used as stent diameter OCT Reference site: Most normal looking segment, No Lipidic plaque Stent sizing: [1] By measuring vessel diameter at the distal reference sites (in case of ≥180° of the external elastic membrane can be identified). In this case, stent diameter will be determined using mean external elastic membrane diameter at the distal reference, rounded down to the nearest 0.25 mm. [2] By measuring lumen diameter at the distal reference sites (in case of ≥180° of the external elastic membrane cannot be identified). In this case, stent diameter will be determined using mean lumen diameter at the distal reference, rounded up to the nearest 0.25 mm.<br>Device: Drug-coated balloon<br>* All patient will be received percutaneous coronary intervention with second generation drug-eluting stent or drug-coated balloon.<br>|
| Active Comparator: Angiography arm<br>The PCI procedure in this group will be performed as standard procedure. After deployment of stent, stent optimization will be done based on angiographic findings. The optimization guided by angiography should meet the criteria of angiographic residual diameter stenosis less than 10% by visual estimation and the absence of flow limiting dissection (≥Type C dissection). When angiographic under-expansion of the stent is suspected, adjunctive balloon dilatation will be strongly recommended. In case of staged procedure during the same hospitalization, following the initially allocated strategy would be strongly recommended. | Procedure: Percutaneous coronary intervention for complex lesion<br>* In patients who have complex coronary lesions, PCI will performed using intravascular imaging or angiography only according to the allocated arms Intravascular imaging arm Angiography arm Definition of Complex Lesions True bifurcation lesion (Medina 1,1,1/1,0,1/0,1,1) with side branch ≥2.5mm size Chronic total occlusion (≥3 months) as target lesion PCI for unprotected left main (LM) disease (LM os, body, distal LM bifurcation including non-true bifurcation) Implanted stent length ≥38mm Multi-vessel PCI (≥2 major epicardial coronary arteries treated at one PCI session) Multiple stent needed (≥3 more stent per patient) In-stent restenosis lesion as target lesion Severely calcified lesion (encircling calcium in angiography) Ostial coronary lesion (LAD, LCX, RCA)<br>Device: Drug-eluting stent<br>* All patient will be received percutaneous coronary intervention with second generation drug-eluting stent or drug-coated balloon.<br>Device: Drug-coated balloon<br>* All patient will be received percutaneous coronary intervention with second generation drug-eluting stent or drug-coated balloon.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Target vessel Failure | A composite of cardiac death, target vessel MI, and clinically-driven target vessel revascularization | 1-year after last patient enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Target vessel failure without procedure-related MI | A composite of cardiac death, spontaneous target vessel MI, and clinically-driven target vessel revascularization | 1-year after last patient enrollment | 
| Cardiac death or target-vessel related MI | Cardiac death or target-vessel related MI | 1-year after last patient enrollment | 
| All-cause death | any death | 1-year after last patient enrollment | 
| Cardiac death | cardiac death | 1-year after last patient enrollment | 
| Target vessel MI with procedure-related MI | Target vessel MI with procedure-related MI | 1-year after last patient enrollment | 
| Target vessel MI without procedure-related MI | Target vessel MI without procedure-related MI | 1-year after last patient enrollment | 
| Any MI with procedure-related MI | Any MI with procedure-related MI | 1-year after last patient enrollment | 
| Any MI without procedure-related MI | Any MI without procedure-related MI | 1-year after last patient enrollment | 
| Non-target vessel related MI | Non-target vessel related MI | 1-year after last patient enrollment | 
| Target lesion revascularization | TLR | 1-year after last patient enrollment | 
| Target vessel revascularization | TVR | 1-year after last patient enrollment | 
| Any revascularization | clinically-driven revascularization | 1-year after last patient enrollment | 
| Stent thrombosis | definite stent thrombosis | 1-year after last patient enrollment | 
| Incidence of contrast-induced nephropathy | CIN was defined as an increase in serum creatinine of ≥0.5mg/dL or ≥25% from baseline within 48-72 hours after contrast agent exposure | 48-72 hours after index procedure | 
| Total amount of contrast use | Total amount of contrast use during index hospitalization | Immediate after index procedure | 
| Total procedure time | Total procedure time during index hospitalization | Immediate after index procedure | 
| Total medical cost | Total medical cost | 1-year after last patient enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intravascular Imaging, Intravascular Ultrasound, Optical Coherence Tomography, Complex Lesion, Percutaneous Coronary Intervention