Coronary Artery Disease
Conditions
Keywords
paclitaxel-eluting stent, PES
Brief summary
The purpose of the TAXUS PERSEUS Small Vessel trial is to evaluate the safety and efficacy of the next-generation Boston Scientific TAXUS paclitaxel-eluting coronary stent system (TAXUS® ElementTM) for the treatment of de novo atherosclerotic lesions of up to 20 mm in length in native coronary arteries of ≥ 2.25 mm to \< 2.75 mm diameter.
Detailed description
This is a prospective, multi-center, single-arm superiority trial to assess the TAXUS® Element™ Paclitaxel-Eluting Coronary Stent System for the treatment of de novo atherosclerotic lesions of ≤20 mm in length in native coronary arteries with visual RVD of ≥ 2.25 mm to \< 2.75 mm diameter. Two hundred twenty-four (224) subjects will be treated with the TAXUS Element stent at a maximum of 35 clinical sites. Follow-up at 30 days, 9 months including angiography) and 1 year will be completed in all subjects enrolled in the study. Eligible subjects will have annual follow-up until 5 years post-index procedure.
Interventions
DEVICEPercutaneous Coronary Intervention (PCI) with paclitaxel-eluting stent (TAXUS Element) implantation
TAXUS Element stent implantation
Sponsors
Boston Scientific Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Clinical Inclusion Criteria: * Subject is ≥ 18 years old * Eligible for percutaneous coronary intervention (PCI) * Documented stable angina pectoris (Canadian Cardiovascular Society \[CCS\] Classification 1, 2, 3, or 4) or unstable angina pectoris (Braunwald Class IB-C, IIB-C, or IIIB-C), or documented silent ischemia * Acceptable candidate for coronary artery bypass grafting (CABG) * Left ventricular ejection fraction (LVEF) is ≥ 30% * Subject (or legal guardian) understands the study requirements and the treatment procedures and provides written Informed Consent before any study-specific tests or procedures are performed * Subject willing to comply with all specified follow-up evaluations Clinical
Exclusion criteria
* Contraindication to aspirin (ASA), or to both clopidogrel and ticlopidine * Known hypersensitivity to paclitaxel * Known allergy to stainless steel * Known allergy to platinum * Previous treatment of the target vessel with any anti-restenotic drug-coated or drug-eluting coronary stent * Previous treatment of the target vessel with a bare metal stent (BMS) within 9 months of the index procedure * Previous treatment of any non-target vessel with any anti-restenotic drug-coated or drug-eluting coronary stent within 9 months of the index procedure * Previous treatment with intravascular brachytherapy in the target vessel * Planned PCI or CABG post-index procedure * Planned or actual target vessel treatment with an unapproved device, directional or rotational coronary atherectomy, laser, cutting balloon or transluminal extraction catheter immediately prior to stent placement * Myocardial infarction (MI) within 72 hours prior to index procedure * Cerebrovascular accident (CVA) within the past 6 months * Cardiogenic shock * Acute or chronic renal dysfunction * Prior anaphylactic reaction to contrast agents * Leukopenia * Thrombocytopenia * Thrombocytosis * Active peptic ulcer or active gastrointestinal (GI) bleeding * Current treatment, or past-treatment within 12-months of the index procedure, with paclitaxel or other chemotherapeutic agents * Anticipated treatment with paclitaxel or oral rapamycin during any period in the 9-months after the index procedure * Known intention to procreate within 9 months after the index procedure * Positive pregnancy test within 7 days before the index procedure, or lactating * Life expectancy of less than 24 months due to other medical conditions * Co-morbid condition(s) that could limit subject's ability to comply with study follow-up requirements or impact study scientific integrity * Currently participating in another investigational drug or device study Angiographic Inclusion Criteria: * Target Lesion * Target lesion located in native coronary artery * Target lesion must be de novo * Target lesion diameter stenosis ≥ 50% * Reference vessel diameter (RVD) ≥ 2.25 mm to \< 2.75 mm * Cumulative target lesion length ≤ 20 mm (area to be treated may be composed of multiple lesions but must be completely coverable by one study stent) * Target lesion is successfully pre-dilated * One non-target lesion may be treated in a non-target vessel as follows: * Non-target lesion in non-target vessel must be treated with commercially available TAXUS stent if use of drug eluting stent required * Treatment must be deemed a clinical angiographic success, without requiring use of unplanned additional stents(s) * Treatment must be completed prior to treatment of target vessel Angiographic
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| In-stent Late Loss Measured by Quantitative Coronary Angiography (QCA) | 9 months post-index procedure | Post-procedure minimum lumen diameter (mm) minus follow-up minimum lumen diameter as determined by quantitative angiography. Minimum lumen diameter is measured within the stent at each time point. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Target Lesion Failure (TLF) at 12 Months Post-index Procedure. TLF is Defined as Any Ischemia-driven Revascularization of the Target Lesion, Myocardial Infarction (Q-wave and Non-Q-wave), or Death Related to the Target Vessel. | 12 months post-index procedure | The number of participants who experience a TLF through 365 days post-procedure out of the patients who have either had a TLF within 365 days post-procedure or who were TLF-free with last follow-up at least 335 days post-procedure. |
Countries
United States
Participant flow
Recruitment details
Eligible subjects were enrolled at 28 United States centers between July 13, 2007 and August 27, 2008. All subjects were required to undergo angiographic assessment at 9 months. The historic control group consists of 125 matched bare metal Express subjects from the TAXUS V trial (NCT00301522), including 108 with 9-month QCA follow-up.
Participants by arm
| Arm | Count |
|---|---|
| TAXUS Element Paclitaxel-eluting stent (PES) implanted using standard percutaneous coronary intervention (PCI) technique | 224 |
| Historical Control Bare Metal Stent (BMS) The control group consists of 125 matched bare metal Express subjects from the TAXUS V trial (NCT00301522). | 125 |
| Total | 349 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 12-Month Clinical Follow-up | Death | 3 | 2 |
| 12-Month Clinical Follow-up | Lost to Follow-up | 2 | 0 |
| 12-Month Clinical Follow-up | Missed 12-Month Visit | 2 | 0 |
| 12-Month Clinical Follow-up | Withdrawal by Subject | 2 | 3 |
| 9-Month Angiographic Follow-up | No 9-Month Angiography Performed | 23 | 12 |
| 9-Month Angiographic Follow-up | Not Evaluable for 9-Month Angiography | 4 | 5 |
Baseline characteristics
| Characteristic | TAXUS Element | Historical Control Bare Metal Stent (BMS) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 124 Participants | 62 Participants | 186 Participants |
| Age, Categorical Between 18 and 65 years | 100 Participants | 63 Participants | 163 Participants |
| Age, Continuous | 64.7 years STANDARD_DEVIATION 10.3 | 64.2 years STANDARD_DEVIATION 10.9 | 64.5 years STANDARD_DEVIATION 10.5 |
| Cardiac History Congestive Heart Failure | 18 participants | 3 participants | 21 participants |
| Cardiac History Previous Coronary Artery Bypass Graft (CABG) | 41 participants | 24 participants | 65 participants |
| Cardiac History Previous Myocardial Infarction (MI) | 57 participants | 36 participants | 93 participants |
| Cardiac History Previous Percutaneous Coronary Intervention (PCI) | 92 participants | 42 participants | 134 participants |
| Cardiac History Silent Ischemia | 43 participants | 18 participants | 61 participants |
| Cardiac History Stable Angina | 136 participants | 70 participants | 206 participants |
| Cardiac History Unstable Angina | 45 participants | 37 participants | 82 participants |
| Cardiac History: Ejection Fraction | 57.9 ejection fraction percent STANDARD_DEVIATION 9.4 | 55.0 ejection fraction percent STANDARD_DEVIATION 9.2 | 56.8 ejection fraction percent STANDARD_DEVIATION 9.4 |
| Cardiac Risk Factors Family History of Coronary Artery Disease | 144 participants | 73 participants | 217 participants |
| Cardiac Risk Factors Hyperlipidemia Requiring Medication | 191 participants | 97 participants | 288 participants |
| Cardiac Risk Factors Hypertension Requiring Medication | 181 participants | 100 participants | 281 participants |
| Cardiac Risk Factors Medically Treated Diabetes | 82 participants | 40 participants | 122 participants |
| Cardiac Risk Factors Smoking, Ever | 137 participants | 69 participants | 206 participants |
| Comorbidities History of Gastrointestinal Bleeding | 5 participants | 2 participants | 7 participants |
| Comorbidities History of Peripheral Vascular Disease | 24 participants | 14 participants | 38 participants |
| Comorbidities History of Renal Disease | 9 participants | 0 participants | 9 participants |
| Comorbidities Transient Ischemic Attack/Cerebrovascular Accident | 21 participants | 5 participants | 26 participants |
| Lesion Characteristic: Lesion Location Distal | 19 participants | 22 participants | 41 participants |
| Lesion Characteristic: Lesion Location Mid | 100 participants | 56 participants | 156 participants |
| Lesion Characteristic: Lesion Location Ostial | 14 participants | 5 participants | 19 participants |
| Lesion Characteristic: Lesion Location Proximal | 91 participants | 42 participants | 133 participants |
| Lesion Characteristic: Pre-Procedure Thrombolysis In Myocardial Infarction (TIMI) Flow TIMI 0 | 1 participants | 0 participants | 1 participants |
| Lesion Characteristic: Pre-Procedure Thrombolysis In Myocardial Infarction (TIMI) Flow TIMI 1 | 2 participants | 1 participants | 3 participants |
| Lesion Characteristic: Pre-Procedure Thrombolysis In Myocardial Infarction (TIMI) Flow TIMI 2 | 1 participants | 7 participants | 8 participants |
| Lesion Characteristic: Pre-Procedure Thrombolysis In Myocardial Infarction (TIMI) Flow TIMI 3 | 220 participants | 117 participants | 337 participants |
| Lesion Characteristics > 45 Degree Bend | 14 participants | 15 participants | 29 participants |
| Lesion Characteristics > 90 Degree Bend | 0 participants | 0 participants | 0 participants |
| Lesion Characteristics Bifurcation | 53 participants | 27 participants | 80 participants |
| Lesion Characteristics Calcification, any | 30 participants | 26 participants | 56 participants |
| Lesion Characteristics Eccentric Lesion | 149 participants | 78 participants | 227 participants |
| Lesion Characteristics Lesion Length | 11.7 millimeters STANDARD_DEVIATION 5.1 | 12.9 millimeters STANDARD_DEVIATION 5.1 | 12.1 millimeters STANDARD_DEVIATION 5.1 |
| Lesion Characteristics Minimum Lumen Diameter | 0.6 millimeters STANDARD_DEVIATION 0.2 | 0.6 millimeters STANDARD_DEVIATION 0.2 | 0.6 millimeters STANDARD_DEVIATION 0.2 |
| Lesion Characteristics Reference Vessel Diameter | 2.1 millimeters STANDARD_DEVIATION 0.3 | 2.2 millimeters STANDARD_DEVIATION 0.4 | 2.1 millimeters STANDARD_DEVIATION 0.3 |
| Lesion Characteristics Sidebranch Stenosis | 18.1 millimeters STANDARD_DEVIATION 24.6 | 16.0 millimeters STANDARD_DEVIATION 21.2 | 17.4 millimeters STANDARD_DEVIATION 23.4 |
| Lesion Characteristics Tortuosity, any | 20 participants | 23 participants | 43 participants |
| Lesion Characteristics Total Occlusion | 3 participants | 1 participants | 4 participants |
| Lesion Characteristics: American College of Cardiology (ACC)/American Heart Association (AHA) Type A | 21 participants | 7 participants | 28 participants |
| Lesion Characteristics: American College of Cardiology (ACC)/American Heart Association (AHA) Type B1 | 73 participants | 21 participants | 94 participants |
| Lesion Characteristics: American College of Cardiology (ACC)/American Heart Association (AHA) Type B2 | 99 participants | 73 participants | 172 participants |
| Lesion Characteristics: American College of Cardiology (ACC)/American Heart Association (AHA) Type C | 31 participants | 24 participants | 55 participants |
| Lesion Characteristic: Target Lesion Vessel Left Anterior Descending | 85 participants | 53 participants | 138 participants |
| Lesion Characteristic: Target Lesion Vessel Left Circumflex | 93 participants | 45 participants | 138 participants |
| Lesion Characteristic: Target Lesion Vessel Right Coronary Artery | 46 participants | 27 participants | 73 participants |
| Percent Diameter Stenosis | 73.5 percent STANDARD_DEVIATION 10.2 | 71.5 percent STANDARD_DEVIATION 10.4 | 72.8 percent STANDARD_DEVIATION 10.3 |
| Race/Ethnicity, Customized American Indian or Alaska native | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Asian | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Black of African heritage | 6 participants | 5 participants | 11 participants |
| Race/Ethnicity, Customized Caucasian | 204 participants | 115 participants | 319 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 11 participants | 3 participants | 14 participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Other | 2 participants | 2 participants | 4 participants |
| Region of Enrollment United States | 224 participants | 125 participants | 349 participants |
| Sex: Female, Male Female | 81 Participants | 49 Participants | 130 Participants |
| Sex: Female, Male Male | 143 Participants | 76 Participants | 219 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 75 / 224 | 41 / 125 |
| serious Total, serious adverse events | 100 / 224 | 70 / 125 |
Outcome results
Primary
In-stent Late Loss Measured by Quantitative Coronary Angiography (QCA)
Post-procedure minimum lumen diameter (mm) minus follow-up minimum lumen diameter as determined by quantitative angiography. Minimum lumen diameter is measured within the stent at each time point.
Time frame: 9 months post-index procedure
Population: The primary analysis population for the superiority testing of the primary endpoint, 9-month in-stent late loss, is the intent-to-treat (ITT) population, i.e. all patients who had a study device implanted at the target lesion and completed their angiographic follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAXUS Element | In-stent Late Loss Measured by Quantitative Coronary Angiography (QCA) | 0.38 millimeter | Standard Deviation 0.51 |
| Historical Control Bare Metal Stent (BMS) | In-stent Late Loss Measured by Quantitative Coronary Angiography (QCA) | 0.80 millimeter | Standard Deviation 0.53 |
Comparison: A superiority test of TAXUX Element vs bare metal (BMS) Express historical control. The null hypothesis that the true difference in means (TAXUS Element - BMS Express) is equal to zero was tested against the two-sided alternative that the true difference in means is different from zero. A sample size of 224 patients in the TAXUS Element group (190 after 15% attrition due to angiographic follow-up) provided 85% power.p-value: <0.000195% CI: [-0.54, -0.3]t-test, 2 sided
Secondary
Number of Participants With Target Lesion Failure (TLF) at 12 Months Post-index Procedure. TLF is Defined as Any Ischemia-driven Revascularization of the Target Lesion, Myocardial Infarction (Q-wave and Non-Q-wave), or Death Related to the Target Vessel.
The number of participants who experience a TLF through 365 days post-procedure out of the patients who have either had a TLF within 365 days post-procedure or who were TLF-free with last follow-up at least 335 days post-procedure.
Time frame: 12 months post-index procedure
Population: Intent-to-Treat. All enrolled patients are included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAXUS Element | Number of Participants With Target Lesion Failure (TLF) at 12 Months Post-index Procedure. TLF is Defined as Any Ischemia-driven Revascularization of the Target Lesion, Myocardial Infarction (Q-wave and Non-Q-wave), or Death Related to the Target Vessel. | 16 participants |
| Historical Control Bare Metal Stent (BMS) | Number of Participants With Target Lesion Failure (TLF) at 12 Months Post-index Procedure. TLF is Defined as Any Ischemia-driven Revascularization of the Target Lesion, Myocardial Infarction (Q-wave and Non-Q-wave), or Death Related to the Target Vessel. | 27 participants |
Comparison: One-sided, single-sample binomial test to compare the observed TLF rate in PERSEUS SV to the pre-specified performance goal (19.5%). The normal approximation of the test statistic was used. The null hypothesis that the true TAXUS Element TLF rate is greater than or equal to the performance goal was tested against the one-sided alternative that the true rate is less than the performance goal. A sample size of 224 patients (accounting for 5% attrition to follow-up) provided 80% power.p-value: <0.0001Chi-squared