Coronary Artery Disease
Conditions
Keywords
drug-eluting stent, paclitaxel-eluting stent, DES
Brief summary
The purpose of the TAXUS PERSEUS Workhorse 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 28 mm in length in native coronary arteries of 2.75 mm to 4.0 mm diameter.
Detailed description
This is a prospective, 3:1 randomization, multi-center trial to assess the TAXUS® Element™ Paclitaxel-Eluting Coronary Stent System for the treatment of de novo atherosclerotic lesions of up to 28 mm in length in native coronary arteries ≥ 2.75 mm and ≤ 4.0 mm in diameter, compared to a control group of TAXUS Express2 Paclitaxel-Eluting Coronary Stent System . One thousand two hundred sixty-four (1264) subjects will be treated with either the TAXUS® Element™ stent or the TAXUS® Express2 ™stent at a maximum of 100 clinical sites. Randomization to treatment group will be unbalanced 3:1 towards the test group to gain maximum clinical experience with the new TAXUS® Element™ platform. Follow-up at 30 days, 9 months and 12 months will be completed in all subjects enrolled in the study. Angiographic follow-up at 9 months will be completed in a subset of three hundred thirty (330) subjects enrolled in the study. Subjects will be randomly allocated to the angiographic subset at participating sites through the Interactive Voice Response System (IVRS). 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 placement
DEVICEPercutaneous coronary intervention (PCI) with paclitaxel-eluting stent (TAXUS Express) placement
TAXUS Express Stent Implant
Sponsors
Boston Scientific Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
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) ≥ 2.75 mm to ≤ 4.0 mm * Cumulative target lesion length ≤ 28 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 |
|---|---|---|
| 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 participants 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| In-segment Percent Diameter Stenosis at 9 Months Post-index Procedure | 9 months post-index procedure | The minimum lumen diameter in the analysis segment at 9-months post-index procedure, divided by the reference vessel diameter at baseline. The analysis segment (in-segment) is defined as the proximal edge, stented area, and the distal edge, where each edge segment contains up to 5mm immediately outside the stent. |
Countries
Australia, New Zealand, Singapore, United States
Participant flow
Recruitment details
Enrollment of 1264 subjects was planned; 1262 (942 TAXUS Element and 320 TAXUS Express) were enrolled and randomized at 90 centers by October 1, 2008. A total of 330 subjects were randomly assigned to protocol-mandated 9-month angiographic follow-up (angiographic subset).
Participants by arm
| Arm | Count |
|---|---|
| TAXUS Element Participants randomized to treatment with TAXUS Element paclitaxel-eluting stent (investigational device) | 942 |
| TAXUS Express Participants randomized to treatment with TAXUS Express paclitaxel-eluting stent (control device) | 320 |
| Total | 1,262 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 12-Month Clinical Follow-up | Death | 6 | 2 |
| 12-Month Clinical Follow-up | Lost to Follow-up | 2 | 1 |
| 12-Month Clinical Follow-up | Missed 12-Month Visit | 13 | 4 |
| 12-Month Clinical Follow-up | Withdrawal by Subject | 4 | 0 |
| 12-Month Clinical Follow-up | Withdrawn at Investigator's discretion | 3 | 2 |
| 9-Month Angiographic Follow-up | No 9-Month Angiography Performed | 25 | 11 |
| 9-Month Angiographic Follow-up | Not Evaluable for Angiography Analysis | 3 | 2 |
Baseline characteristics
| Characteristic | TAXUS Element | Total | TAXUS Express |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 402 Participants | 559 Participants | 157 Participants |
| Age, Categorical Between 18 and 65 years | 540 Participants | 703 Participants | 163 Participants |
| Age, Continuous | 62.2 years STANDARD_DEVIATION 9.6 | 62.5 years STANDARD_DEVIATION 9.6 | 63.5 years STANDARD_DEVIATION 9.5 |
| Cardiac History Congestive Heart Failure | 56 participants | 80 participants | 24 participants |
| Cardiac History Previous Coronary Artery Bypass Graft (CABG) | 42 participants | 62 participants | 20 participants |
| Cardiac History Previous Myocardial Infarction (MI) | 195 participants | 255 participants | 60 participants |
| Cardiac History Previous Percutaneous Coronary Intervention (PCI) | 216 participants | 296 participants | 80 participants |
| Cardiac History Silent Ischemia | 117 participants | 156 participants | 39 participants |
| Cardiac History Stable Angina | 629 participants | 842 participants | 213 participants |
| Cardiac History Unstable Angina | 195 participants | 263 participants | 68 participants |
| Cardiac History: Ejection Fraction | 58.0 ejection fraction percent STANDARD_DEVIATION 9.3 | 57.9 ejection fraction percent STANDARD_DEVIATION 9.4 | 57.8 ejection fraction percent STANDARD_DEVIATION 9.8 |
| Cardiac Risk Factors Family History of Coronary Artery Disease | 589 participants | 785 participants | 196 participants |
| Cardiac Risk Factors Hyperlipidemia Requiring Medication | 717 participants | 960 participants | 243 participants |
| Cardiac Risk Factors Hypertension Requiring Medication | 709 participants | 965 participants | 256 participants |
| Cardiac Risk Factors Medically Treated Diabetes | 232 participants | 312 participants | 80 participants |
| Cardiac Risk Factors Smoking, Ever | 611 participants | 827 participants | 216 participants |
| Comorbidities History of Cerebrovascular Accident | 30 participants | 42 participants | 12 participants |
| Comorbidities History of Gastrointestinal Bleeding | 9 participants | 16 participants | 7 participants |
| Comorbidities History of Peripheral Vascular Disease | 99 participants | 135 participants | 36 participants |
| Comorbidities History of Renal Disease | 45 participants | 56 participants | 11 participants |
| Comorbidities History of Transient Ischemic Attack | 30 participants | 44 participants | 14 participants |
| Lesion Characteristic: Lesion Location Distal | 64 participants | 94 participants | 30 participants |
| Lesion Characteristic: Lesion Location Mid | 485 participants | 639 participants | 154 participants |
| Lesion Characteristic: Lesion Location Ostial | 25 participants | 33 participants | 8 participants |
| Lesion Characteristic: Lesion Location Proximal | 368 participants | 496 participants | 128 participants |
| Lesion Characteristic: Percent Diameter Stenosis | 72.1 percent STANDARD_DEVIATION 10.9 | 72.0 percent STANDARD_DEVIATION 10.9 | 71.7 percent STANDARD_DEVIATION 10.9 |
| Lesion Characteristic - Pre-Procedure Thrombolysis In Myocardial Infarction (TIMI) Flow TIMI 0 | 2 participants | 4 participants | 2 participants |
| Lesion Characteristic - Pre-Procedure Thrombolysis In Myocardial Infarction (TIMI) Flow TIMI 1 | 4 participants | 4 participants | 0 participants |
| Lesion Characteristic - Pre-Procedure Thrombolysis In Myocardial Infarction (TIMI) Flow TIMI 2 | 34 participants | 38 participants | 4 participants |
| Lesion Characteristic - Pre-Procedure Thrombolysis In Myocardial Infarction (TIMI) Flow TIMI 3 | 902 participants | 1216 participants | 314 participants |
| Lesion Characteristics > 45 Degree Bend | 61 participants | 83 participants | 22 participants |
| Lesion Characteristics > 90 Degree Bend | 2 participants | 3 participants | 1 participants |
| Lesion Characteristics Bifurcation | 343 participants | 472 participants | 129 participants |
| Lesion Characteristics Calcification, any | 228 participants | 314 participants | 86 participants |
| Lesion Characteristics Eccentric Lesion | 487 participants | 648 participants | 161 participants |
| Lesion Characteristics Lesion Length | 14.2 millimeter STANDARD_DEVIATION 6.1 | 14.2 millimeter STANDARD_DEVIATION 6 | 14.1 millimeter STANDARD_DEVIATION 5.8 |
| Lesion Characteristics Minimum Lumen Diameter | 0.8 millimeter STANDARD_DEVIATION 0.3 | 0.8 millimeter STANDARD_DEVIATION 0.3 | 0.8 millimeter STANDARD_DEVIATION 0.4 |
| Lesion Characteristics Reference Vessel Diameter | 2.8 millimeter STANDARD_DEVIATION 0.5 | 2.8 millimeter STANDARD_DEVIATION 0.5 | 2.8 millimeter STANDARD_DEVIATION 0.5 |
| Lesion Characteristics Sidebranch Stenosis | 24.4 millimeter STANDARD_DEVIATION 28.1 | 24.7 millimeter STANDARD_DEVIATION 28.3 | 25.7 millimeter STANDARD_DEVIATION 28.8 |
| Lesion Characteristics Tortuosity, any | 59 participants | 73 participants | 14 participants |
| Lesion Characteristics Total Occlusion | 6 participants | 8 participants | 2 participants |
| Lesion Characteristics: American College of Cardiology (ACC)/American Heart Association (AHA) Class Type A | 79 participants | 107 participants | 28 participants |
| Lesion Characteristics: American College of Cardiology (ACC)/American Heart Association (AHA) Class Type B1 | 233 participants | 318 participants | 85 participants |
| Lesion Characteristics: American College of Cardiology (ACC)/American Heart Association (AHA) Class Type B2 | 384 participants | 514 participants | 130 participants |
| Lesion Characteristics: American College of Cardiology (ACC)/American Heart Association (AHA) Class Type C | 246 participants | 323 participants | 77 participants |
| Lesion Characteristic: Target Lesion Vessel Left Anterior Descending Artery | 406 participants | 546 participants | 140 participants |
| Lesion Characteristic: Target Lesion Vessel Left Circumflex Artery | 217 participants | 286 participants | 69 participants |
| Lesion Characteristic: Target Lesion Vessel Right Coronary Artery | 319 participants | 430 participants | 111 participants |
| Race/Ethnicity, Customized American Indian or Alaska native | 3 participants | 3 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 15 participants | 21 participants | 6 participants |
| Race/Ethnicity, Customized Black of African heritage | 37 participants | 50 participants | 13 participants |
| Race/Ethnicity, Customized Caucasian | 872 participants | 1168 participants | 296 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 10 participants | 16 participants | 6 participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 4 participants | 5 participants | 1 participants |
| Race/Ethnicity, Customized Other | 4 participants | 4 participants | 0 participants |
| Region of Enrollment Australia | 60 participants | 82 participants | 22 participants |
| Region of Enrollment New Zealand | 17 participants | 23 participants | 6 participants |
| Region of Enrollment Singapore | 6 participants | 8 participants | 2 participants |
| Region of Enrollment United States | 859 participants | 1149 participants | 290 participants |
| Sex: Female, Male Female | 275 Participants | 375 Participants | 100 Participants |
| Sex: Female, Male Male | 667 Participants | 887 Participants | 220 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 277 / 942 | 97 / 320 |
| serious Total, serious adverse events | 334 / 942 | 110 / 320 |
Outcome results
Primary
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 participants 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: The primary analysis set for the non-inferiority testing of the primary endpoint, 12-month TLF, is the per protocol analysis set. All randomized participants who had the randomly assigned study stent implanted in the target coronary artery are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAXUS Element | 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. | 51 participants |
| TAXUS Express | 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. | 19 participants |
Comparison: Bayesian modeling was used to determine if the 12-month TLF rate for the TAXUS Element stent was non-inferior to the 12-month TLF rate in the TAXUS Express2 control. The null hypothesis was that the TAXUS Element TLF rate is at least 4.1% greater than the TAXUS Express TLF rate. The alternative hypothesis was that the TAXUS Element TLF rate is less than 4.1% greater than the TAXUS Express TLF rate.p-value: 0.9996Bayesian modeling
Secondary
In-segment Percent Diameter Stenosis at 9 Months Post-index Procedure
The minimum lumen diameter in the analysis segment at 9-months post-index procedure, divided by the reference vessel diameter at baseline. The analysis segment (in-segment) is defined as the proximal edge, stented area, and the distal edge, where each edge segment contains up to 5mm immediately outside the stent.
Time frame: 9 months post-index procedure
Population: All patients from the per protocol analysis set who were randomized to the angiographic subset and completed their angiographic follow-up were analyzed for the secondary endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAXUS Element | In-segment Percent Diameter Stenosis at 9 Months Post-index Procedure | 26.1 percent diameter stenosis | Standard Deviation 17.71 |
| TAXUS Express | In-segment Percent Diameter Stenosis at 9 Months Post-index Procedure | 26.28 percent diameter stenosis | Standard Deviation 17.6 |
Comparison: Natural log (ln) transformation was used to improve normality of the secondary endpoint distribution. Bayesian modeling was used to determine if the mean ln(9-month percent diameter stenosis) for the TAXUS Element stent was non-inferior to the mean ln(9-month %DS) for TAXUS Express. Null hypothesis was that the TAXUS Element mean was at least 0.20 greater than the TAXUS Express mean. Alternative hypothesis was that the TAXUS Element mean is less than 0.20 greater than the TAXUS Express TLF mean.p-value: 0.997Bayesian modeling