Wall Shear Stress and Neointimal Healing Following PCI in Angulated Coronary Vessels (SHEAR-STENT)

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

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 86
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Nanjing, China, 310006
    • Nanjing Medical University, Nanjing Heart Center
• Japan
  • Hyōgo, Japan, 650-0017
    • Kobe University Graduate School of Medicine
  • Wakayama, Japan, 641-8509
    • Wakayama Medical University Department of Cardiovascular Medicine
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University College of Medicine
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center, Sungkyunkwan University School of Medicine Division of Cardiology
  • Ulsan, Korea, Republic of, 44033
    • Ulsan University Hospital University of Ulsan College of Medicine
• Latvia
  • Riga, Latvia, 1002
    • Latvian Society of Cardiology Pauls Stradins Clinical University Hospital
• Serbia
  • Belgrade, Serbia, 11000
    • University Clinical Center of Serbia
• Spain
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos, Universidad Complutense de Madrid
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30605
      • Emory University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Resolute Integrity DES; Resolute Integrity zotarolimus eluting stent	Device: Resolute Integrity Zotarolimus eluting stent; PCI with Resolute stent; Device: Optical Coherence Tomography (OCT); 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.; Device: Intravascular Ultrasound (IVUS); 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.
Active Comparator: Xience Xpedition DES; Xience Xpedition everolimus eluting stent	Device: Optical Coherence Tomography (OCT); 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.; Device: Intravascular Ultrasound (IVUS); 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.; Device: Xience Xpedition everolimus eluting stent; PCI with Xience stent

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: Medtronic
• Investigators: Principal Investigator: Habib Samady, MD, Georgia Heart Institute, Northeast Georgia Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2014
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: January 10, 2014
• First Submitted That Met QC Criteria: March 27, 2014
• First Posted (Estimate): March 28, 2014

Study Record Updates

• Last Update Posted (Actual): September 9, 2022
• Last Update Submitted That Met QC Criteria: August 16, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: everolimus eluting stent; wall shear stress; neointimal tissue area; angulated coronary vessels; zotarolimus eluting stent
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Everolimus
• Other Study ID Numbers: IRB00066353

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes