Coronary Artery Disease, Coronary Artery Restenosis, Coronary Artery Stenosis, Coronary Disease
Conditions
Keywords
Stents, Drug-eluting Stent, Angioplasty, Coronary Artery stenosis, Coronary Artery Stent Restenosis, Stent Thrombosis
Brief summary
The purpose of this two part study is the assessment of the performance of the XIENCE V® Everolimus Eluting Coronary Stent System (XIENCE V® EECSS) in the treatment of the specific setting of patients with Multi-Vessel Coronary Artery Disease (MVD).
Detailed description
This is a clinical evaluation of the XIENCE V® everolimus eluting coronary stent system as a revascularization treatment of patients with multi-vessel coronary artery disease (MVD-CAD). The long term safety and efficacy of the XIENCE V EECSS have been demonstrated in the SPIRIT FIRST trial up to 5 years, the SPIRIT II trial up to 4 years, and in the SPIRIT III Randomized Control Trial (RCT) up to 3 years. In addition, these pre-approval studies have shown low rates of Target Vessel Failure and Major Adverse Cardiac Events (MACE) that were consistently lower than the comparator arm of each study. The post approval EXECUTIVE study demonstrated that the use of the XIENCE EECSS in complex lesions in a real-world population resulted in 1 year MACE, Stent Thrombosis and Target Lesion Revascularization rates that are comparable to those of the previously mentioned pre-approval studies which included patients with more restricted inclusion / exclusion criteria. Therefore, based on existing data from these trials, Abbott Vascular has decided to discontinue further follow up in the EXECUTIVE trial. The study is composed of two parts: A Registry, outlined in a separate posting and the Randomized Control Trial (RCT) portion of this study, which is as follows: -A randomized group of patients aimed at assessing the angiographic efficacy of the XIENCE V® Everolimus Eluting Coronary Stent System (XIENCE V® EECSS) compared to the TAXUS® Liberté™ Paclitaxel Eluting Coronary Stent System.
Interventions
DEVICEXIENCE V® Everolimus Eluting Coronary Stent System
Coronary artery placement of a drug-eluting stent
DEVICETAXUS® Liberté™ Paclitaxel Eluting Coronary Stent System
Coronary artery placement of a drug-eluting stent
Sponsors
Abbott Medical Devices
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patient must be at least 18 years of age 2. Patient is able to verbally confirm understanding of risks, benefits and treatment alternatives of receiving the XIENCE V® EECSS and he/she or his/her legally authorized representative provides written informed consent prior to any study related procedure, as approved by the appropriate Medical Ethics Committee of the respective clinical site 3. Patient has been diagnosed a MVD, as documented by coronary angiography, i.e. presenting a severe stenosis (\>50%) amenable to PCI in at least 2 major epicardial vessels or their principal bifurcation branches (diagonal or obtuse marginal) 4. Patient must have evidence of myocardial ischemia (e.g., stable or unstable angina, silent ischemia, positive functional study or a reversible change in the electrocardiogram -ECG- consistent with ischemia) 5. Patient must be an acceptable candidate for coronary artery bypass graft (CABG) surgery 6. Patient must agree to undergo all protocol-required follow-up examinations. Angiographic Inclusion Criteria 1. Patients may receive up to 4 planned XIENCE V® EECSS stents, depending on the number of vessels treated and their respective lesion length. When multiple lesions are present in one or more main coronary branches, complete revascularization should be attempted with the implantation of a maximum of 4 planned stents 2. Target lesions must be de novo lesions (no prior stent implant, no prior brachytherapy) 3. Target vessel reference diameter must be between 2.5 mm and 4.0 mm by visual estimate 4. Target lesion \< or = 28 mm in length by visual estimation 5. Target lesions must be in a major artery or its principal branches (diagonal or obtuse marginal) with a visually estimated stenosis of \> or = 50% 6. Two lesions in a single main coronary artery or its branches do not constitute a MVD situation, therefore this type of patient must not be enrolled
Exclusion criteria
1. Patient has had a known diagnosis of acute myocardial infarction (AMI) within 72 hours preceding the index procedure (non-procedural/spontaneous MI, CK-MB \> or = to 2 times upper limit of normal) and CK and CK-MB have not returned within normal limits at the time of procedure 2. Patient has current unstable arrhythmias 3. Patient has a known left ventricular ejection fraction (LVEF) \<30% 4. Patient has received a heart transplant or any other organ transplant or is on a waiting list for any organ transplant 5. Patient is receiving or scheduled to receive chemotherapy or radiation therapy within 30 days prior to or after the procedure. 6. Patient is receiving immunosuppression therapy or has known immunosuppressive or autoimmune disease (e.g. human immunodeficiency virus, systemic lupus erythematosus etc.) 7. Patient is receiving chronic anticoagulation therapy (e.g. coumadin) 8. Patient has a known hypersensitivity or contraindication to aspirin, paclitaxel, either heparin or bivalirudin, clopidogrel or ticlopidine, everolimus, cobalt, chromium, nickel, tungsten, acrylic and fluoro polymers or contrast sensitivity that cannot be adequately pre-medicated 9. Elective surgery is planned within the first 9 months (+/- 14 days) after the procedure that will require discontinuing either aspirin or clopidogrel 10. Patient has a platelet count \<100,000 cells/mm3 or \>700,000 cells/mm3, a WBC of \<3,000 cells/mm3, or documented or suspected liver disease (including laboratory evidence of hepatitis) 11. Patient has known renal insufficiency (e.g., serum creatinine level of more than 2.5 mg/dl, patient on dialysis) 12. Patient has a history of bleeding diathesis or coagulopathy or will refuse blood transfusions 13. Patient has had a cerebrovascular accident (CVA) or transient ischemic neurological attack (TIA) within the past six months 14. Patient has had a significant GI or urinary bleed within the past six months 15. Patient has other medical illness (e.g., cancer or congestive heart failure) or known history of substance abuse (alcohol, cocaine, heroin etc.) that may cause non-compliance with the protocol, confound the data interpretation or is associated with a limited life expectancy (i.e. less than one year) 16. Patient is already participating in another investigational use device or drug study or has completed the follow-up phase of another study within the last 30 days. Angiographic
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| In-stent Late Loss (LL) | at 270 days | Full Analysis Set (FAS). LL is defined as the difference between the post-procedure (immediately post placement of the stent) minimal lumen diameter (MLD) and the follow-up MLD (at 270 days). In stent is measured within the confines of the stent edges. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| In-segment Binary Restenosis Rate | at 9 months | This measures the percentage of patients who have \> 50% diameter stenosis of the assessed vessel, within the stent edges In-segment is measured within the confines of the stent edges plus within 5 mm on either side of the stent. |
| In-segment Late Loss (LL) | at 9 months | LL is defined as the difference between the post-procedure (immediately post placement of the stent) minimal lumen diameter (MLD) and the follow-up MLD (at 270 days). In segment LL is measured within the confines of the stent edges and within 5 mm of those edges. |
| Composite Rate of Cardiac Death, Myocardial Infarction (MI, Both Q-wave and Non Q-wave), and Ischemia-driven Target Lesion Revascularization (TLR) . | at 30 days | This measure is a calculation of the percentage of participants who experience any of the components of this composite measure. |
| Composite Rate of All Death, MI (Q-wave and Non Q-wave), and Target Vessel Revascularization (TVR). | at 30 days | — |
| Lesion Success | at the time of PCI | defined as attainment of \< 30% residual in-stent stenosis (by visual assessment) using any percutaneous method. |
| Procedural Success | at the time of PCI | defined as: residual in-stent %DS of \< 30% using a percutaneous method, without cardiac death, Q-wave MI, non Q-wave MI, or repeat revasc of the target during hospitalization. |
| Device Success | at the time of PCI | defined as achievement of a final residual in-stent diameter stenosis of \< 30% (visual assessment) using the assigned device only. |
| In-stent Binary Restenosis Rate | at 9 months | This measures the percentage of patients who have \> 50% diameter stenosis of the assessed vessel, within the stent edges. |
| Revascularizations | at 30 days | (TLR/TVR/any revascularization)both ischemia-driven and not ischemia-driven. |
| Composite Endpoint of Cardiac Death, MI (Q-wave and Non Q-wave), and Ischemia-driven TLR . | 9 months | ITT |
| Composite Endpoint of All Death, MI (Q-wave and Non Q-wave), and TVR. | 9 months | — |
| In-stent Minimum Lumen Diameter (MLD). | at 9 months. | — |
| In-segment Minimum Lumen Diameter (MLD). | at 9 months. | — |
| Proximal Minimum Lumen Diameter (MLD). | at 9 months. | Proximal refers to the immediate 5 mm outside of the proximal end of the stent. |
| Distal Minimum Lumen Diameter (MLD). | at 9 months. | Distal refers to the immediate 5 mm outside of the distal end of the stent. |
| Adjudicated Stent Thrombosis. | at 30 days | — |
Countries
Italy
Participant flow
Recruitment details
The patient population was comprised of male and female patients derived from the general interventional cardiology population from 9 centers in Italy.
Participants by arm
| Arm | Count |
|---|---|
| XIENCE V Patients randomized to receive the XIENCE V® Everolimus Eluting Coronary Stent System (XIENCE V® EECSS) | 103 |
| TAXUS® Liberté™ Patients randomized to receive the TAXUS® Liberté™ Paclitaxel Eluting Coronary Stent System | 97 |
| Total | 200 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 0 | 3 |
| Overall Study | Withdrawal by Subject | 2 | 4 |
Baseline characteristics
| Characteristic | TAXUS® Liberté™ | XIENCE V | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 49 Participants | 57 Participants | 106 Participants |
| Age, Categorical Between 18 and 65 years | 48 Participants | 46 Participants | 94 Participants |
| Age, Continuous | 63.8 years STANDARD_DEVIATION 10.2 | 64.7 years STANDARD_DEVIATION 10.1 | 64.2 years STANDARD_DEVIATION 10.2 |
| Region of Enrollment Italy | 97 participants | 103 participants | 200 participants |
| Sex: Female, Male Female | 24 Participants | 27 Participants | 51 Participants |
| Sex: Female, Male Male | 73 Participants | 76 Participants | 149 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 21 / 101 | 19 / 91 |
Outcome results
Primary
In-stent Late Loss (LL)
Full Analysis Set (FAS). LL is defined as the difference between the post-procedure (immediately post placement of the stent) minimal lumen diameter (MLD) and the follow-up MLD (at 270 days). In stent is measured within the confines of the stent edges.
Time frame: at 270 days
Population: Descriptive statistics for this measure are based on one random lesion per patient, 167 patients performed angiographic follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| XIENCE V | In-stent Late Loss (LL) | 0.052 millimeters | Standard Deviation 0.513 |
| TAXUS® Liberté™ | In-stent Late Loss (LL) | 0.238 millimeters | Standard Deviation 0.504 |
Secondary
Adjudicated Stent Thrombosis.
Time frame: 9 months
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| XIENCE V | Adjudicated Stent Thrombosis. | 0 percentage of participants |
| TAXUS® Liberté™ | Adjudicated Stent Thrombosis. | 0 percentage of participants |
Secondary
Adjudicated Stent Thrombosis.
Time frame: at 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| XIENCE V | Adjudicated Stent Thrombosis. | 0 percentage of participants |
| TAXUS® Liberté™ | Adjudicated Stent Thrombosis. | 0 percentage of participants |
Secondary
Composite Endpoint of All Death, MI (Q-wave and Non Q-wave), and TVR.
Time frame: 9 months
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| XIENCE V | Composite Endpoint of All Death, MI (Q-wave and Non Q-wave), and TVR. | 6.8 percentage of participants |
| TAXUS® Liberté™ | Composite Endpoint of All Death, MI (Q-wave and Non Q-wave), and TVR. | 12.4 percentage of participants |
Secondary
Composite Endpoint of Cardiac Death, MI (Q-wave and Non Q-wave), and Ischemia-driven TLR .
ITT
Time frame: 9 months
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| XIENCE V | Composite Endpoint of Cardiac Death, MI (Q-wave and Non Q-wave), and Ischemia-driven TLR . | 4.9 percentage of participants |
| TAXUS® Liberté™ | Composite Endpoint of Cardiac Death, MI (Q-wave and Non Q-wave), and Ischemia-driven TLR . | 7.2 percentage of participants |
Secondary
Composite Rate of All Death, MI (Q-wave and Non Q-wave), and Target Vessel Revascularization (TVR).
Time frame: at 30 days
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| XIENCE V | Composite Rate of All Death, MI (Q-wave and Non Q-wave), and Target Vessel Revascularization (TVR). | 1 percentage of participants |
| TAXUS® Liberté™ | Composite Rate of All Death, MI (Q-wave and Non Q-wave), and Target Vessel Revascularization (TVR). | 2.1 percentage of participants |
Secondary
Composite Rate of Cardiac Death, Myocardial Infarction (MI, Both Q-wave and Non Q-wave), and Ischemia-driven Target Lesion Revascularization (TLR) .
This measure is a calculation of the percentage of participants who experience any of the components of this composite measure.
Time frame: at 30 days
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| XIENCE V | Composite Rate of Cardiac Death, Myocardial Infarction (MI, Both Q-wave and Non Q-wave), and Ischemia-driven Target Lesion Revascularization (TLR) . | 1 percentage of participants |
| TAXUS® Liberté™ | Composite Rate of Cardiac Death, Myocardial Infarction (MI, Both Q-wave and Non Q-wave), and Ischemia-driven Target Lesion Revascularization (TLR) . | 2.1 percentage of participants |
Secondary
Device Success
defined as achievement of a final residual in-stent diameter stenosis of \< 30% (visual assessment) using the assigned device only.
Time frame: at the time of PCI
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| XIENCE V | Device Success | 97.7 percentage of participants |
| TAXUS® Liberté™ | Device Success | 98.2 percentage of participants |
Secondary
Distal Minimum Lumen Diameter (MLD).
Distal refers to the immediate 5 mm outside of the distal end of the stent.
Time frame: at 9 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| XIENCE V | Distal Minimum Lumen Diameter (MLD). | 2.28 millimeters | Standard Deviation 0.59 |
| TAXUS® Liberté™ | Distal Minimum Lumen Diameter (MLD). | 2.25 millimeters | Standard Deviation 0.57 |
Secondary
In-segment Binary Restenosis Rate
This measures the percentage of patients who have \> 50% diameter stenosis of the assessed vessel, within the stent edges In-segment is measured within the confines of the stent edges plus within 5 mm on either side of the stent.
Time frame: at 9 months
Population: 167 patients performed angiographic follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| XIENCE V | In-segment Binary Restenosis Rate | 6.2 percentage of participants |
| TAXUS® Liberté™ | In-segment Binary Restenosis Rate | 4.6 percentage of participants |
Secondary
In-segment Late Loss (LL)
LL is defined as the difference between the post-procedure (immediately post placement of the stent) minimal lumen diameter (MLD) and the follow-up MLD (at 270 days). In segment LL is measured within the confines of the stent edges and within 5 mm of those edges.
Time frame: at 9 months
Population: 167 patients performed angiographic follow-up. Descriptive statistics for this measure are based on one random lesion per patient.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| XIENCE V | In-segment Late Loss (LL) | -0.100 millimeters | Standard Deviation 0.484 |
| TAXUS® Liberté™ | In-segment Late Loss (LL) | 0.037 millimeters | Standard Deviation 0.421 |
Secondary
In-segment Minimum Lumen Diameter (MLD).
Time frame: at 9 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| XIENCE V | In-segment Minimum Lumen Diameter (MLD). | 2.10 millimeters | Standard Deviation 0.57 |
| TAXUS® Liberté™ | In-segment Minimum Lumen Diameter (MLD). | 2.04 millimeters | Standard Deviation 0.52 |
Secondary
In-stent Binary Restenosis Rate
This measures the percentage of patients who have \> 50% diameter stenosis of the assessed vessel, within the stent edges.
Time frame: at 9 months
Population: ITT, 167 patients performed angiographic follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| XIENCE V | In-stent Binary Restenosis Rate | 5.8 percentage of participants |
| TAXUS® Liberté™ | In-stent Binary Restenosis Rate | 3.6 percentage of participants |
Secondary
In-stent Minimum Lumen Diameter (MLD).
Time frame: at 9 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| XIENCE V | In-stent Minimum Lumen Diameter (MLD). | 2.29 millimeters | Standard Deviation 0.64 |
| TAXUS® Liberté™ | In-stent Minimum Lumen Diameter (MLD). | 2.17 millimeters | Standard Deviation 0.61 |
Secondary
Lesion Success
defined as attainment of \< 30% residual in-stent stenosis (by visual assessment) using any percutaneous method.
Time frame: at the time of PCI
Population: Intent to treat (ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| XIENCE V | Lesion Success | 99.2 Percentage of participants |
| TAXUS® Liberté™ | Lesion Success | 99.6 Percentage of participants |
Secondary
Procedural Success
defined as: residual in-stent %DS of \< 30% using a percutaneous method, without cardiac death, Q-wave MI, non Q-wave MI, or repeat revasc of the target during hospitalization.
Time frame: at the time of PCI
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| XIENCE V | Procedural Success | 98.1 percentage of participants |
| TAXUS® Liberté™ | Procedural Success | 97 percentage of participants |
Secondary
Proximal Minimum Lumen Diameter (MLD).
Proximal refers to the immediate 5 mm outside of the proximal end of the stent.
Time frame: at 9 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| XIENCE V | Proximal Minimum Lumen Diameter (MLD). | 2.67 millimeters | Standard Deviation 0.65 |
| TAXUS® Liberté™ | Proximal Minimum Lumen Diameter (MLD). | 2.61 millimeters | Standard Deviation 0.62 |
Secondary
Revascularizations
(TLR/TVR/any revascularization)both ischemia-driven and not ischemia-driven.
Time frame: at 30 days
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| XIENCE V | Revascularizations | 0 percentage of participants |
| TAXUS® Liberté™ | Revascularizations | 0 percentage of participants |
Secondary
Revascularizations
(TLR/TVR/any revascularization)both ischemia-driven and not ischemia-driven.
Time frame: 9 months
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| XIENCE V | Revascularizations | 5.8 percentage of participants |
| TAXUS® Liberté™ | Revascularizations | 11.3 percentage of participants |