Coronary Artery Disease
Conditions
Keywords
neointimal tissue area, angulated coronary vessels, wall shear stress, zotarolimus eluting stent, everolimus eluting stent
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.
Interventions
DEVICEResolute Integrity Zotarolimus eluting stent
PCI with Resolute stent
DEVICEXience Xpedition everolimus eluting stent
PCI with Xience stent
DEVICEOptical 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.
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.
Sponsors
Medtronic
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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) |
| 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). |
| 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 |
Countries
China, Japan, Latvia, Serbia, South Korea, Spain, United States
Participant flow
Recruitment details
Participants were recruited from 12 SITES. Participant enrollment began in May 2014 and all follow up was complete by December 2020.
Participants by arm
| Arm | Count |
|---|---|
| Resolute Integrity DES Resolute Integrity zotarolimus eluting stent
Resolute Integrity Zotarolimus eluting stent: PCI with Resolute stent
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.
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. | 45 |
| Xience Xpedition DES Xience Xpedition everolimus eluting stent
Xience Xpedition everolimus eluting stent: PCI with Xience stent
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.
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. | 41 |
| Total | 86 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 5 | 5 |
Baseline characteristics
| Characteristic | Resolute Integrity DES | Total | Xience Xpedition DES |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 19 Participants | 37 Participants | 18 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants | 49 Participants | 23 Participants |
| Age, Continuous | 62.6 years STANDARD_DEVIATION 11.6 | 63.2 years STANDARD_DEVIATION 11.1 | 63.8 years STANDARD_DEVIATION 10.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 30 Participants | 61 Participants | 31 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 12 Participants | 20 Participants | 8 Participants |
| Region of Enrollment China | 9 participants | 15 participants | 6 participants |
| Region of Enrollment Japan | 8 participants | 20 participants | 12 participants |
| Region of Enrollment Latvia | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Serbia | 7 participants | 13 participants | 6 participants |
| Region of Enrollment South Korea | 13 participants | 26 participants | 13 participants |
| Region of Enrollment Spain | 1 participants | 1 participants | 0 participants |
| Region of Enrollment United States | 6 participants | 10 participants | 4 participants |
| Sex: Female, Male Female | 9 Participants | 16 Participants | 7 Participants |
| Sex: Female, Male Male | 36 Participants | 70 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 0 / 41 |
| other Total, other adverse events | 0 / 45 | 2 / 41 |
| serious Total, serious adverse events | 2 / 45 | 2 / 41 |
Outcome results
Primary
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
Time frame: 1 year
Population: The numbers for each different endpoint are dependent on the data quality and availability for each endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Resolute Integrity DES | In Stent Mean Cross-sectional Area of Neo-intimal Tissue Coverage | 1.381 mm^2 | Standard Deviation 1.026 |
| Xience Xpedition DES | In Stent Mean Cross-sectional Area of Neo-intimal Tissue Coverage | 0.949 mm^2 | Standard Deviation 0.767 |
Secondary
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)
Time frame: Immediately after stent implantation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Resolute Integrity DES | In-Stent: Degree of Vascular Straightening Post-percutaneous Coronary Intervention (PCI) (In-Stent Mechanistic Endpoint) | 40 Degree | Standard Deviation 25 |
| Xience Xpedition DES | In-Stent: Degree of Vascular Straightening Post-percutaneous Coronary Intervention (PCI) (In-Stent Mechanistic Endpoint) | 36 Degree | Standard Deviation 33 |
Secondary
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)
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Resolute Integrity DES | In Stent: Mean Thickness of Strut Coverage at Follow up | 0.118 mm^2 | Standard Deviation 0.109 |
| Xience Xpedition DES | In Stent: Mean Thickness of Strut Coverage at Follow up | 0.096 mm^2 | Standard Deviation 0.09 |
Secondary
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)
Time frame: Immediately after stent implantation
Population: This outcome required that patients received computational fluid dynamics analysis, unfortunately, this was not possible in all patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Resolute Integrity DES | In-Stent: Percent Area of Low Wall Shear Stress (WSS)-(In-Stent Mechanistic Endpoint) | 0.9 percentage of area | Standard Deviation 0.13 |
| Xience Xpedition DES | In-Stent: Percent Area of Low Wall Shear Stress (WSS)-(In-Stent Mechanistic Endpoint) | 0.9 percentage of area | Standard Deviation 0.11 |
Secondary
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)
Time frame: Immediately after stent implantation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Resolute Integrity DES | In Stent: Plaque Prolapse Post-PCI (In-Stent Mechanistic Endpoint) | 0.12 mm^2 | Standard Deviation 0.14 |
| Xience Xpedition DES | In Stent: Plaque Prolapse Post-PCI (In-Stent Mechanistic Endpoint) | 0.13 mm^2 | Standard Deviation 0.16 |
Secondary
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
Time frame: 1 year
Population: The number of participants with images that are of adequate quality for analysis. The number reported corresponds to the actual change in plaque area between baseline and 1 year follow-up
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Resolute Integrity DES | Stent Edge -Change in Plaque Area (Efficacy Endpoint) at 5 mm Proximal and Distal to Stent. | -0.8 mm^2 | Standard Deviation 1.7 |
| Xience Xpedition DES | Stent Edge -Change in Plaque Area (Efficacy Endpoint) at 5 mm Proximal and Distal to Stent. | -0.5 mm^2 | Standard Deviation 2.8 |
Secondary
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
Time frame: Immediately after stent implantation
Population: This outcome only requires baseline angiograms hence more patients meet this criteria.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Resolute Integrity DES | Stent Edge: Degree of Vascular Straightening Post-percutaneous Coronary Intervention (PCI) at the Stent Edges (Stent Edge Mechanistic Endpoint) | 22 Degrees | Standard Deviation 14 |
| Xience Xpedition DES | Stent Edge: Degree of Vascular Straightening Post-percutaneous Coronary Intervention (PCI) at the Stent Edges (Stent Edge Mechanistic Endpoint) | 21 Degrees | Standard Deviation 14 |
Secondary
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).
Time frame: Immediately after stent implantation
Population: This outcome required that patients received computational fluid dynamics analysis, unfortunately, this was not possible in all patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Resolute Integrity DES | Stent Edge: Percent Area With Low Wall Shear Stress (WSS) at Stent Edges Post-PCI (Mechanistic Endpoint) | 0.6 percentage of area | Standard Deviation 0.23 |
| Xience Xpedition DES | Stent Edge: Percent Area With Low Wall Shear Stress (WSS) at Stent Edges Post-PCI (Mechanistic Endpoint) | 0.64 percentage of area | Standard Deviation 0.29 |