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

• ClinicalTrials.gov Identifier: NCT02098876
• Recruitment Status: Completed
• First Posted: March 28, 2014
• Results First Posted: September 9, 2022
• Last Update Posted: September 9, 2022
• Sponsor: Emory University
• Collaborator: Medtronic
• Information provided by (Responsible Party): Habib Samady, Emory University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Coronary Artery Disease	Device: Resolute Integrity Zotarolimus eluting stent; Device: Xience Xpedition everolimus eluting stent; Device: Optical Coherence Tomography (OCT); Device: Intravascular Ultrasound (IVUS)	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 86 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 2014
• Actual Primary Completion Date: December 2020
• Actual Study Completion Date: December 2020

Arms and Interventions

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: Xience Xpedition everolimus eluting stent; PCI with Xience 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.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30605

China

Nanjing Medical University, Nanjing Heart Center

Nanjing, China, 310006

Japan

Kobe University Graduate School of Medicine

Hyōgo, Japan, 650-0017

Wakayama Medical University Department of Cardiovascular Medicine

Wakayama, Japan, 641-8509

Korea, Republic of

Seoul National University College of Medicine

Seoul, Korea, Republic of, 03080

Samsung Medical Center, Sungkyunkwan University School of Medicine Division of Cardiology

Seoul, Korea, Republic of, 06351

Ulsan University Hospital University of Ulsan College of Medicine

Ulsan, Korea, Republic of, 44033

Latvia

Latvian Society of Cardiology Pauls Stradins Clinical University Hospital

Riga, Latvia, 1002

Serbia

University Clinical Center of Serbia

Belgrade, Serbia, 11000

Spain

Hospital Clinico San Carlos, Universidad Complutense de Madrid

Madrid, Spain, 28040

Sponsors and Collaborators

Emory University

Medtronic

Investigators

• Principal Investigator: Habib Samady, MD; Georgia Heart Institute, Northeast Georgia Medical Center

  Study Documents (Full-Text)

Documents provided by Habib Samady, Emory University:

Study Protocol and Statistical Analysis Plan  [PDF] September 4, 2020

Informed Consent Form  [PDF] December 10, 2015

More Information

• Responsible Party: Habib Samady, Professor, Emory University
• ClinicalTrials.gov Identifier: NCT02098876
• Other Study ID Numbers: IRB00066353
• First Posted: March 28, 2014
• Results First Posted: September 9, 2022
• Last Update Posted: September 9, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Keywords provided by Habib Samady, Emory University:

neointimal tissue area; angulated coronary vessels; wall shear stress; zotarolimus eluting stent; everolimus eluting stent

Additional relevant MeSH terms:

Coronary Artery Disease; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Everolimus; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs