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

Not Applicable

Completed

• Conditions: Coronary Artery Disease
• Interventions: Device: Resolute Integrity Zotarolimus eluting stent; Device: Xience Xpedition everolimus eluting stent; Device: Optical Coherence Tomography (OCT); Device: Intravascular Ultrasound (IVUS)

• Registration Number: NCT02098876
• Lead Sponsor: Emory University

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2014-01-10
• Study First Submitted QC: 2014-03-27
• Study First Posted: 2014-03-28
• Study Start: 2014-05
• Primary Completion: 2020-12
• Study Completion: 2020-12
• Disposition First Submitted: 2021-11-17
• Disposition First Submitted QC: 2021-12-01
• Disposition First Posted: 2021-12-07
• Results First Submitted: 2022-06-30
• Status Verified: 2022-08
• Results First Submitted QC: 2022-08-16
• Last Update Submitted: 2022-08-16
• Results First Posted: 2022-09-09
• Last Update Posted: 2022-09-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 86

Inclusion Criteria

1. Patient must be 30 to 80 years old
2. Severe coronary lesion in a vessel with ≥ 30-degree angulation requiring percutaneous coronary intervention (PCI)
3. Lesion treatable by a single Resolute Integrity or Onyx Abbott Xience Xpedition or Sierra coronary drug-eluting stent.
4. Patients with stable ischemic heart disease or acute coronary syndrome undergoing clinically PCI.

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Exclusion Criteria

1. Inability to provide informed consent prior to randomization
2. Anatomy requiring coronary artery bypass surgery (CABG)
3. History of prior CABG in the territory of the vessel being considered for PCI
4. Heavily calcified lesion requiring rotablation or other debulking or scoring device for successful stent deployment
5. Large thrombus burden on recent angiography
6. Previously stented vessels
7. 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)
8. Lesions at bifurcations and those that occlude side branches >2.5mm
9. Recent (<72 hours) ST-elevation myocardial infarction (STEMI).
10. Planned surgical procedures in the subsequent 12 months
11. History of hypersensitivity or contraindication to device materials and their degradants, everolimus, zotarolimus, cobalt, chromium, nickel, platinum, tungsten, acrylic, and fluoropolymers
12. History of any solid organ transplantation or subject is on a waiting list for any solid organ transplant
13. Left ventricular ejection fraction < 30%
14. Known allergies to clinically utilized anti-thrombotic or anti-platelet agents
15. Unable to tolerate long term dual antiplatelet therapy
16. Pregnancy or lactation

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Xience Xpedition DES	Optical Coherence Tomography (OCT)	Xience Xpedition everolimus eluting stent
Resolute Integrity DES	Intravascular Ultrasound (IVUS)	Resolute Integrity zotarolimus eluting stent
Resolute Integrity DES	Resolute Integrity Zotarolimus eluting stent	Resolute Integrity zotarolimus eluting stent
Resolute Integrity DES	Optical Coherence Tomography (OCT)	Resolute Integrity zotarolimus eluting stent
Xience Xpedition DES	Xience Xpedition everolimus eluting stent	Xience Xpedition everolimus eluting stent
Xience Xpedition DES	Intravascular Ultrasound (IVUS)	Xience Xpedition everolimus eluting stent

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
In Stent: Mean Thickness of Strut Coverage at Follow up	1 year	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)
In-Stent: Degree of Vascular Straightening Post-percutaneous Coronary Intervention (PCI) (In-Stent Mechanistic Endpoint)	Immediately after stent implantation	post PCI angulation by Angio: In-Stent: Degree of vascular straightening post-percutaneous coronary intervention (PCI) (In-Stent mechanistic endpoint)
In Stent: Plaque Prolapse Post-PCI (In-Stent Mechanistic Endpoint)	Immediately after stent implantation	Plaque will be identified by Optical Coherence Tomography (OCT)- In-Stent: Plaque prolapse post-PCI (In-Stent mechanistic endpoint)
In-Stent: Percent Area of Low Wall Shear Stress (WSS)-(In-Stent Mechanistic Endpoint)	Immediately after stent implantation	The % area of low wall shear stress immediately after stent implantation will be measured by Optical Coherence Tomography (OCT)
Stent Edge -Change in Plaque Area (Efficacy Endpoint) at 5 mm Proximal and Distal to Stent.	1 year	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
Stent Edge: Degree of Vascular Straightening Post-percutaneous Coronary Intervention (PCI) at the Stent Edges (Stent Edge Mechanistic Endpoint)	Immediately after stent implantation	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
Stent Edge: Percent Area With Low Wall Shear Stress (WSS) at Stent Edges Post-PCI (Mechanistic Endpoint)	Immediately after stent implantation	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).

Trial Locations

Locations (10)

Latvian Society of Cardiology Pauls Stradins Clinical University Hospital; 🇱🇻 Riga, Latvia

Wakayama Medical University Department of Cardiovascular Medicine; 🇯🇵 Wakayama, Japan

Kobe University Graduate School of Medicine; 🇯🇵 Hyōgo, Japan

Ulsan University Hospital University of Ulsan College of Medicine; 🇰🇷 Ulsan, Korea, Republic of

Emory University; 🇺🇸 Atlanta, Georgia, United States

Seoul National University College of Medicine; 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center, Sungkyunkwan University School of Medicine Division of Cardiology; 🇰🇷 Seoul, Korea, Republic of

Hospital Clinico San Carlos, Universidad Complutense de Madrid; 🇪🇸 Madrid, Spain

University Clinical Center of Serbia; 🇷🇸 Belgrade, Serbia

Nanjing Medical University, Nanjing Heart Center; 🇨🇳 Nanjing, China