Peripheral Vascular Diseases
Conditions
Keywords
Peripheral Arterial Disease (PAD), Peripheral Vascular Disease, Drug-Eluting Stent, Drug-Coated Stent
Brief summary
The Zilver® PTX™ Drug Eluting Vascular Stent is indicated for the treatment of symptomatic vascular disease of the above-the-knee femoropopliteal artery (ranging from 4 mm to 9 mm in reference vessel diameter) for lesions up to 7 cm long. The clinical trial is stratified by lesion length. The trial will be conducted in 2 phases, with Phase 1 enrolling patients with lesions less than 7 cm long. Phase 2 of the trial will include longer lesions (up to 14 cm long) and will be initiated upon approval by the Food and Drug Administration (FDA).
Detailed description
The Zilver® PTX™ Drug Eluting Vascular Stent is indicated for the treatment of symptomatic vascular disease of the above-the-knee femoropopliteal artery (ranging from 4 mm to 9 mm in reference vessel diameter) for lesions up to 7 cm long. The above-the-knee femoropopliteal artery is defined as the superficial femoral artery (SFA) and the region of the popliteal artery above the plane of the femoral epicondyles. The clinical trial is stratified by lesion length. The trial will be conducted in 2 phases, with Phase 1 enrolling patients with lesions less than 7 cm long. Phase 2 of the trial will include longer lesions (up to 14 cm long) and will be initiated upon approval by the FDA. This study will include 480 patients who will receive the Zilver PTX stent or Percutaneous transluminal angioplasty (PTA) at up to 100 investigational sites. Clinical data will be captured on paper and electronic case report forms. Analyses will include evaluation of the composite event-free survival rate and the patency rate at 6- and 12-month follow-up. Event-free survival is defined as freedom from the major adverse events of death, target lesion revascularization, target limb ischemia requiring surgical intervention (bypass or amputation of toe, foot or leg), surgical repair of the target vessel (e.g., dissection requiring surgery), and from worsening of the Rutherford classification by 2 classes or to class 5 or 6. Patency will be assessed by duplex ultrasound in all patients. Patients may be randomized to one or more of the following sub-studies: IVUS and angiography at 6 months (stent patients only), angiography at 12 months, pharmacokinetic substudy (Zilver PTX patients only), or ultrasound (PTA patients only). The trial also includes provisions for patients experiencing PTA failure. These patients may be randomized to receive a Zilver PTX stent or a bare Zilver stent.
Interventions
DEVICEZilver® PTX™ Drug Eluting Vascular Stent
Stenting of the Superfemoropopliteal Artery
PROCEDUREAngioplasty
Angioplasty of the Superfemoropopliteal Artery
Sponsors
William Cook Europe
MED Institute, Incorporated
Cook Japan Incorporated
Cook Group Incorporated
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
* Patient has signed and dated the informed consent. * Patient has up to 2 documented stenotic or occluded atherosclerotic lesions (up ro 14 cm long) of the above-the-knee femoropopliteal artery, up to one in each limb, that meet all of the inclusion criteria and none of the
Exclusion criteria
. * Patient has a de novo or restenotic lesion(s) with \>50% stenosis documented angiographically and no prior stent in the target lesion. * Patient has symptoms of peripheral arterial disease classified as Rutherford Category 2 or greater. * Patient has a resting Ankle Brachial Index (ABI) \<0.9 or an abnormal exercise ABI if resting ABI is normal. Patient with incompressible arteries (ABI \>1.2) must have a Toe Brachial Index (TBI) \<0.8. * Patient agrees to return for a clinical status assessment and duplex ultrasound at 6 months, 12 months, and at 2, 3, 4, and 5 years. * Patient agrees to return for x-rays at 6 and 12 months. * Patient agrees to return for angiography at 12 months. * Patient agrees to be contacted by telephone at 1, 3, 9, and 18 months to assess clinical status.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-free Survival Rate | 12 months | Event-free survival is defined as freedom from the major adverse events of death, target lesion revascularization, target limb ischemia requiring surgical intervention (bypass or amputation of toe, foot or leg), surgical repair of the target vessel (e.g., dissection requiring surgery), and from worsening of the Rutherford classification by 2 classes or to class 5 or 6. Participant flow is based on initial randomization of Zilver PTX or PTA (Percutaneous balloon angioplasty), and Event-free survival is based on Per-Protocol analysis where only patients who were treated according to their initial randomization are counted. |
| Primary Patency | 12 months | Primary patency is defined as a Peak systolic velocity (PSV) ratio \< 2.0 or angiographic percent diameter stenosis \< 50%. |
Countries
Germany, Japan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Zilver PTX Zilver® PTX™ Drug Eluting Vascular Stent | 236 |
| PTA (Control) Percutaneous balloon angioplasty | 238 |
| Total | 474 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 9 | 4 |
| Overall Study | Lost to Follow-up | 5 | 2 |
| Overall Study | patient moved but has not withdrawn | 0 | 1 |
| Overall Study | received non-study stent | 0 | 2 |
| Overall Study | Withdrawal by Subject | 5 | 7 |
Baseline characteristics
| Characteristic | Total | Zilver PTX | PTA (Control) |
|---|---|---|---|
| Age, Continuous | 67.8 years STANDARD_DEVIATION 10.1 | 67.9 years STANDARD_DEVIATION 9.6 | 67.7 years STANDARD_DEVIATION 10.6 |
| BMI | 28.3 kg/m^2 STANDARD_DEVIATION 5.4 | 28.4 kg/m^2 STANDARD_DEVIATION 5.3 | 28.2 kg/m^2 STANDARD_DEVIATION 5.6 |
| Calcification Little | 157 lesions | 62 lesions | 95 lesions |
| Calcification Moderate | 140 lesions | 85 lesions | 55 lesions |
| Calcification None | 16 lesions | 4 lesions | 12 lesions |
| Calcification Severe | 177 lesions | 90 lesions | 87 lesions |
| Diabetes Patients with diabetes | 217 participants | 117 participants | 100 participants |
| Diabetes Patients without diabetes | 257 participants | 119 participants | 138 participants |
| Hypercholesterolemia Patients with hypercholesterolemia | 346 participants | 180 participants | 166 participants |
| Hypercholesterolemia Patients without hypercholesterolemia | 128 participants | 56 participants | 72 participants |
| Hypertension Patients with hypertension | 404 participants | 210 participants | 194 participants |
| Hypertension Patients without hypertension | 70 participants | 26 participants | 44 participants |
| Normal-to-normal Lesion length | 64.8 mm STANDARD_DEVIATION 39.7 | 66.4 mm STANDARD_DEVIATION 38.9 | 63.2 mm STANDARD_DEVIATION 40.5 |
| Percent diameter stenosis | 79.1 percent of proximal ref. vessel diameter STANDARD_DEVIATION 17 | 79.8 percent of proximal ref. vessel diameter STANDARD_DEVIATION 17 | 78.4 percent of proximal ref. vessel diameter STANDARD_DEVIATION 17.1 |
| Sex: Female, Male Female | 167 Participants | 81 Participants | 86 Participants |
| Sex: Female, Male Male | 307 Participants | 155 Participants | 152 Participants |
| Smoking status Never smoked | 69 participants | 32 participants | 37 participants |
| Smoking status Quit | 254 participants | 131 participants | 123 participants |
| Smoking status Still smokes | 150 participants | 73 participants | 77 participants |
| Smoking status Unknown | 1 participants | 0 participants | 1 participants |
| Stenosed lesion length | 53.9 mm STANDARD_DEVIATION 40.5 | 54.6 mm STANDARD_DEVIATION 40.7 | 53.2 mm STANDARD_DEVIATION 40.3 |
| Total Occlusion Lesions without total occlusion | 342 lesions | 162 lesions | 180 lesions |
| Total Occlusion Lesions with total occlusion | 147 lesions | 79 lesions | 68 lesions |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 81 / 235 | 72 / 236 |
| serious Total, serious adverse events | 21 / 235 | 37 / 236 |
Outcome results
Primary
Event-free Survival Rate
Event-free survival is defined as freedom from the major adverse events of death, target lesion revascularization, target limb ischemia requiring surgical intervention (bypass or amputation of toe, foot or leg), surgical repair of the target vessel (e.g., dissection requiring surgery), and from worsening of the Rutherford classification by 2 classes or to class 5 or 6. Participant flow is based on initial randomization of Zilver PTX or PTA (Percutaneous balloon angioplasty), and Event-free survival is based on Per-Protocol analysis where only patients who were treated according to their initial randomization are counted.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zilver PTX | Event-free Survival Rate | 90.4 Percentage of participants |
| PTA (Control) | Event-free Survival Rate | 83.9 Percentage of participants |
p-value: <0.01z-test, one-sided
Primary
Primary Patency
Primary patency is defined as a Peak systolic velocity (PSV) ratio \< 2.0 or angiographic percent diameter stenosis \< 50%.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zilver PTX | Primary Patency | 82.7 Percentage of participants |
| PTA (Control) | Primary Patency | 32.7 Percentage of participants |
p-value: <0.01Generalized estimating equation (GEE)