Wall Shear Stress and Neointimal Healing Following PCI in Angulated Coronary Vessels

Study Overview
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Brief Summary
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Stents are metallic tubular supports placed inside a blood vessel to relieve an obstruction and restore blood flow to the heart muscle. Stents could also be coated with a drug (drug-eluting stents - DES) that improves local healing and inhibits growth of scar tissue within the vessel that otherwise could lead to re-narrowing. This study will evaluate the effects of 2 FDA-approved metallic stents with different designs that may have important effects on regional plaque response and blood flow dynamics immediately after stent deployment and stent healing at 12 months follow up.

Detailed Description
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The past two decades have registered major advances in cardiovascular medicine that have improved patients' survival and quality of life. One area of major research and innovation is the field of percutaneous coronary interventions (PCI), a non-surgical procedure used to treat a narrowed heart artery with stents. Stents are metallic tubular supports placed inside a blood vessel to relieve an obstruction and restore blood flow to the heart muscle. Stents could also be coated with a drug (drug-eluting stents - DES) that improves local healing and inhibits growth of scar tissue (smooth muscle and fibrous cells) within the vessel that otherwise could lead to re-narrowing. The investigators study will evaluate two FDA-approved DES, currently in use, with respect to coronary vessel healing and long term patency. These include the XIENCE Xpedition Everolimus drug-eluting stent (X-EES) from Abbott Vascular and Resolute Integrity® Zotarolimus drug-eluting stent (R-ZES) from Medtronic, Inc, both of which have been shown in large clinical trials to be safe and effective. This study will evaluate the effects of apparently subtle differences in stent design between these two platforms that may have important effects on regional plaque response and blood flow dynamics immediately after stent deployment and stent healing and scar formation at 12 months follow up. Several aspect of the R-ZES compared to the X-EES design may result in more favorable regional plaque response and blood flow dynamics immediately after stent deployment. These include a more compliant stent design made of a single sinusoidal wire with no connector between struts that is likely to be more comformable to a curved or angulated coronary vessels. In heart vessels which are not angulated, these features may not make a major difference in outcomes as studies already suggest. Whereas, in narrowed arteries which are curved or angulated, the use of X-EES could result in more straightening of the vessel's natural curvature and more disturbance in flow patterns. In contrast, the use of R-ZES in angulated arteries could cause less hemodynamic disturbances. There is a great deal of data suggesting that disturbances in local blood flow patterns and creation of eddy currents ('turbulent' blood flow) could adversely affect stent healing and exacerbate neointimal tissue growth. Using two intravascular imaging technologies, the optical coherence tomography (OCT) and intravascular ultrasound (IVUS), this study aims to investigate differences in scar tissue coverage within the stented region and the degree of narrowing at the edges of the stent in patients undergoing clinically-indicated PCI (with R-ZES and X-EES) at 12-month follow-up.

Official Title
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Evaluation of WSS and Neointimal Healing Following Percutaneous Coronary Intervention of Angulated Vessels With Resolute® Integrity Zotarolimus Eluting Coronary Stent Compared to XIENCE Xpedition® Everolimus Eluting Coronary Stent

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Device: Resolute Integrity Zotarolimus eluting stent
* Device: Xience Xpedition everolimus eluting stent
* Device: Optical Coherence Tomography (OCT)
* Device: Intravascular Ultrasound (IVUS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must be 30 to 80 years old Severe coronary lesion in a vessel with ≥ 30-degree angulation requiring percutaneous coronary intervention (PCI) Lesion treatable by a single Resolute Integrity or Onyx Abbott Xience Xpedition or Sierra coronary drug-eluting stent. Patients with stable ischemic heart disease or acute coronary syndrome undergoing clinically PCI. Exclusion Criteria: Inability to provide informed consent prior to randomization Anatomy requiring coronary artery bypass surgery (CABG) History of prior CABG in the territory of the vessel being considered for PCI Heavily calcified lesion requiring rotablation or other debulking or scoring device for successful stent deployment Large thrombus burden on recent angiography Previously stented vessels Ostial lesions: lesion located within 5mm of the origin of the left anterior descending artery (LAD), left circumflex artery (LCx), or Right coronary artery (RCA) Lesions at bifurcations and those that occlude side branches >2.5mm Recent (<72 hours) ST-elevation myocardial infarction (STEMI). Planned surgical procedures in the subsequent 12 months History of hypersensitivity or contraindication to device materials and their degradants, everolimus, zotarolimus, cobalt, chromium, nickel, platinum, tungsten, acrylic, and fluoropolymers History of any solid organ transplantation or subject is on a waiting list for any solid organ transplant Left ventricular ejection fraction < 30% Known allergies to clinically utilized anti-thrombotic or anti-platelet agents Unable to tolerate long term dual antiplatelet therapy Pregnancy or lactation

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Resolute Integrity DES<br>Resolute Integrity zotarolimus eluting stent | Device: Resolute Integrity Zotarolimus eluting stent<br>* PCI with Resolute stent<br>Device: Optical Coherence Tomography (OCT)<br>* Optical coherence tomography (OCT) will be performed at baseline to assess plaque burden prior to and after stent deployment as well as to evaluate stent expansion and stent apposition. OCT will be repeated at one year follow-up to evaluate neo-intimal tissue coverage within the stent and change in plaque area at the stent edges. Offline, manual detection of lumen area and stent area will be performed for each OCT cross-section from baseline and follow up examinations.<br>Device: Intravascular Ultrasound (IVUS)<br>* Intravascular ultrasound (IVUS) will be performed at baseline to assess plaque burden prior to and after stent deployment as well as to evaluate stent expansion and stent apposition. IVUS will be repeated at one year follow-up to evaluate neo-intimal tissue coverage within the stent and change in plaque area at the stent edges. Offline, manual detection of lumen area, stent area, vessel area (external elastic membrane) and the media-adventitia interface will be performed for each IVUS cross-section from baseline and follow up examinations.<br>|
| Active Comparator: Xience Xpedition DES<br>Xience Xpedition everolimus eluting stent | Device: Xience Xpedition everolimus eluting stent<br>* PCI with Xience stent<br>Device: Optical Coherence Tomography (OCT)<br>* Optical coherence tomography (OCT) will be performed at baseline to assess plaque burden prior to and after stent deployment as well as to evaluate stent expansion and stent apposition. OCT will be repeated at one year follow-up to evaluate neo-intimal tissue coverage within the stent and change in plaque area at the stent edges. Offline, manual detection of lumen area and stent area will be performed for each OCT cross-section from baseline and follow up examinations.<br>Device: Intravascular Ultrasound (IVUS)<br>* Intravascular ultrasound (IVUS) will be performed at baseline to assess plaque burden prior to and after stent deployment as well as to evaluate stent expansion and stent apposition. IVUS will be repeated at one year follow-up to evaluate neo-intimal tissue coverage within the stent and change in plaque area at the stent edges. Offline, manual detection of lumen area, stent area, vessel area (external elastic membrane) and the media-adventitia interface will be performed for each IVUS cross-section from baseline and follow up examinations.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In Stent Mean Cross-sectional Area of Neo-intimal Tissue Coverage | Cross-sectional area in neointimal hyperplasia by Optical Coherence Tomography (OCT) at 1 year following stent placement | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In Stent: Mean Thickness of Strut Coverage at Follow up | Mean thickness of strut coverage at follow up (In-Stent safety endpoint). Struts have been considered as covered when tissue overlying the struts is >0 μm by optical coherence tomography (OCT) | 1 year | 
| In-Stent: Degree of Vascular Straightening Post-percutaneous Coronary Intervention (PCI) (In-Stent Mechanistic Endpoint) | post PCI angulation by Angio: In-Stent: Degree of vascular straightening post-percutaneous coronary intervention (PCI) (In-Stent mechanistic endpoint) | Immediately after stent implantation | 
| In Stent: Plaque Prolapse Post-PCI (In-Stent Mechanistic Endpoint) | Plaque will be identified by Optical Coherence Tomography (OCT)- In-Stent: Plaque prolapse post-PCI (In-Stent mechanistic endpoint) | Immediately after stent implantation | 
| In-Stent: Percent Area of Low Wall Shear Stress (WSS)-(In-Stent Mechanistic Endpoint) | The % area of low wall shear stress immediately after stent implantation will be measured by Optical Coherence Tomography (OCT) | Immediately after stent implantation | 
| Stent Edge -Change in Plaque Area (Efficacy Endpoint) at 5 mm Proximal and Distal to Stent. | Change in plaque area at the stent edges will be calculated from the change in plaque area in the 5 mm proximal and distal segments by intravascular ultrasound (IVUS); calculated as follow-up values minus baseline values | 1 year | 
| Stent Edge: Degree of Vascular Straightening Post-percutaneous Coronary Intervention (PCI) at the Stent Edges (Stent Edge Mechanistic Endpoint) | Degree of vascular straightening post-percutaneous coronary intervention (PCI) at the stent edges (Stent Edge mechanistic endpoint) will be measured post PCI angulation by Angio | Immediately after stent implantation | 
| Stent Edge: Percent Area With Low Wall Shear Stress (WSS) at Stent Edges Post-PCI (Mechanistic Endpoint) | The % area of low wall shear stress in the 5 mm proximal and distal segments immediately after stent implantation will be measured by intravascular ultrasound (IVUS). | Immediately after stent implantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neointimal tissue area, angulated coronary vessels, wall shear stress, zotarolimus eluting stent, everolimus eluting stent