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

Sponsor

Emory University (Other)

Overall Status

Completed

CT.gov ID

NCT02098876

Collaborator

Medtronic (Industry)

Enrollment

Locations

Arms

Duration (Months)

8.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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)	N/A

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

Actual Enrollment :

81 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

Study Start Date :

May 1, 2014

Actual Primary Completion Date :

Dec 1, 2020

Actual Study Completion Date :

Dec 1, 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.

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)

Device: Intravascular Ultrasound (IVUS)

Outcome Measures

Primary Outcome Measures

In Stent mean cross-sectional area of neo-intimal tissue coverage [1 year]
Coefficient of variance in neointimal hyperplasia by Optical Coherence Tomography (OCT) at 1 year following stent placement

Secondary Outcome Measures

In Stent: Mean thickness of strut coverage at follow up (In-Stent safety endpoint) [Immediately after stent implantation and at 1 year]
Number and percent of uncovered and malposed struts using 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: Plaque prolapse post-PCI (In-Stent mechanistic endpoint) [Immediately after stent implantation]
Plaque will be identified by Optical Coherence Tomography (OCT)
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]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Georgia Heart Institute, Gainesville Georgia	Atlanta	Georgia	United States	30605
2	Nanjing Medical University, Nanjing Heart Center	Nanjing		China	310006
3	Kobe University Graduate School of Medicine	Hyōgo		Japan	650-0017
4	Wakayama Medical University Department of Cardiovascular Medicine	Wakayama		Japan	641-8509
5	Seoul National University College of Medicine	Seoul		Korea, Republic of	03080
6	Samsung Medical Center, Sungkyunkwan University School of Medicine Division of Cardiology	Seoul		Korea, Republic of	06351
7	Ulsan University Hospital University of Ulsan College of Medicine	Ulsan		Korea, Republic of	44033
8	Latvian Society of Cardiology Pauls Stradins Clinical University Hospital	Riga		Latvia	1002
9	University Clinical Center of Serbia	Belgrade		Serbia	11000
10	Hospital Clinico San Carlos, Universidad Complutense de Madrid	Madrid		Spain	28040