Ischemic Stroke, Transient Ischemic Attack
Conditions
Keywords
Ischemic stroke, Transient Ischemic Attack, Intracranial Stenting
Brief summary
The main objective of this study is to prospectively evaluate the safety, probable benefit, and effectiveness of the PHAROS Vitesse Neurovascular Stent System in a multicenter, randomized clinical trial. A secondary objective of this study is to evaluate the impact of stenting in the neurovasculature to treat cerebral ischemia on other outcomes such as hospital length of stay, charges, and costs.
Detailed description
1.1 Study Hypothesis Treatment of cerebral or retinal ischemia due to plaque in the neurovasculature using the PHAROS Vitesse Stent System plus medical therapy will provide additional clinical benefit over medical therapy alone. 1.2 Primary Effectiveness Endpoint The primary effectiveness endpoint consists of a composite of the two following outcomes: * Stroke in the same territory (distal to the target lesion) as the presenting event within 12 months of randomization * Hard TIA in the same territory (distal to the target lesion) as the presenting event from day 2 through month 12 post-randomization 1.3 Safety Outcomes Safety outcomes to be collected and reported as part of the overall risk-to-benefit profile for this device are: * Stroke in any territory within 30 days of randomization * Death from any cause within 30 days of randomization * Hard TIA in any territory occurring after a 24 hour post-procedure stabilization period (days 2-30) since the recovery from anesthesia can mask accurate assessment of possible TIA symptoms. * Intracranial hemorrhage within 30 days of randomization 1.4 Other Outcomes * Stent Success - PHAROS Vitesse stent deployed across target lesion with residual stenosis 0-20% * Percentage of Stent Group Subjects with any (symptomatic or asymptomatic) in-stent restenosis ≥ 70% confirmed by angiogram at 12 months * Percentage of Stent Group Subjects with symptomatic in-stent restenosis ≥ 70% confirmed by angiogram at 12 months * Percentage of Medical Therapy Group Subjects with interventional procedure (e.g., angioplasty or stent) at 12 months * Comparison of NIHSS scores between treatment arms * Comparison of mRS scores between treatment arms
Interventions
DEVICEPharos Vitesse Neurovascular Stent System (Stent implantation) + Medical therapy (Aspirin and Clopidogrel)
Implantation of one or more balloon-expandable Pharos Vitesse stents to treat neurovascular ischemic lesions + Medical therapy \[Treatment with aspirin (81-325 mg daily for the duration of the study) and Clopidogrel (75 mg daily for first 3 months)\]
DRUGAspirin and Clopidogrel (Medical therapy)
Medical therapy alone \[Treatment with aspirin (81-325 mg daily for the duration of the study) and Clopidogrel (75 mg daily for first 3 months)\]
Sponsors
Codman & Shurtleff
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Subject has at least one neurovascular lesion (70-99%) stenosis \[internal carotid, middle cerebral, vertebral artery (C4-BA), and/or basilar artery\] symptomatic with a hard TIA or stroke attributable to the territory of the lesion within the past 30 days. An intracranial tandem lesion (50-99%) stenosis may be treated if normal artery segment is sufficient length to avoid overlapping stents. 2. Target vessel diameter / lesion length measurements are within one of the below per angiogram: * Vessel diameter is ≥ 2.0 mm and \< 2.5 mm / lesion length is ≤ 16 mm, or * Vessel diameter is ≥ 2.5 mm and \< 3.0 mm / lesion length is ≤ 18 mm, or * Vessel diameter is ≥ 3.0 mm and \< 4.5 mm / lesion length is ≤ 26 mm, or * Vessel diameter is ≥ 4.5 mm and ≤ 5.0 mm / lesion length is ≤ 31 mm 3. Subject has normal artery adjacent to each stenosis; diameter 2.0 mm - 5.0 mm 4. Subject age is 18-85 years 5. Life expectancy is at least 2 years 6. Subject 's mRS score is ≤ 3 7. Subject is available for study follow-up visits (e.g., lives within 3 hours of research center) 8. Subject is willing and cognitively able to provide Informed Consent (consent may be indicated verbally and signed by neutral witness if stroke has impaired hand or visual function)
Exclusion criteria
1. Subject has contraindications for balloon expandable stent, e.g. * Extreme tortuosity at, or proximal to, target lesion, * More than 2 lesions with \> 50% stenosis (including vertebral ostia and common carotid disease), * Carotid or vertebral dissection 2. CT scan or MRI evidence of any of the following: * Intracranial hemorrhage of type PH1 or PH2 * Subdural or epidural hemorrhage * Mass effect, or * Intracranial tumor (except small meningioma) 3. Subject has a previous stent in the territory of the target lesion(s) 4. Subject has a previous coil or clip placed in the territory of the target lesion within 6 months 5. Subject has a potential source of cardiac embolism requiring anticoagulation therapy (e.g., atrial fibrillation, intracardiac thrombus or vegetation, significant mitral stenosis, mechanical heart valve, congestive heart failure with EF \<30%, or endocarditis) 6. Subject has concurrent intracranial pathology, e.g. * Moyamoya * Vasculitis documented by biopsy results * Ruptured Aneurysm * Unruptured aneurysm \> 7mm 7. Subject has uncontrolled hypertension (systolic \>185 mmHg or diastolic \>110 mmHg) 8. Hemoglobin \< 10 g/dL; platelet count \< 100,000; or INR \> 1.5 (e.g., use of warfarin) 9. Subject has an uncorrectable bleeding diathesis 10. Subject's neurological status is unstable and rapidly declining (NIHSS score increased \> 4 points within 48 hours prior to randomization) 11. Subject has a contraindication for combination antithrombotic treatment (e.g., clopidogrel and aspirin) such as peptic ulcer disease 12. Subject history indicates high risk of non-compliance (e.g., substance abuse, psychosocial issues, etc.) 13. Subject has a known history contraindicating contrast dye or iodine (vs. sensitivity which can be safely controlled by antihistamine, steroid, etc.) 14. Subject is pregnant or plans to become pregnant in the next 12 months 15. Myocardial infarction within past 3 months 16. Treatment with tPA or other thrombolytic agent within 48 hours prior to randomization 17. Major surgery or trauma within 2 weeks prior to randomization 18. Enrollment in another investigational device or drug study that may confound the results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Successful Outcome: No Stroke or Hard TIA in the Same Territory Within 12 Months | One Year | The primary effectiveness endpoint was a composite of the two following outcomes: * Stroke in the same territory (distal to the target lesion) as the presenting event within 12 months of randomization * Hard Transient Ischemic Attack (TIA) in the same territory (distal to the target lesion) as the presenting event from day 2 through month 12 post-randomization A subject was deemed to be a primary endpoint success if neither of these outcomes occurred. The Kaplan-Meier success rate at 12-months post-operatively was calculated with Kaplan-Meier time-to-event methodology, where the time variable for patients who were successful (no stroke within 12 months or hard TIA between 2 days and 12 months) was censored at the time of last follow-up, and the time variable for patients who were not successful (had a stroke within 12 months or hard TIA between 2 days and 12 months) was censored at the time of the first event (stroke with 12 months or hard TIA between 2 days and 12 months). |
Participant flow
Recruitment details
Subjects were screened and enrolled at 27 sites worldwide (23 sites in the US and 4 sites outside of the US).
Pre-assignment details
125 consented,of which 112 were randomized.Of 112,110 were treated (64 Stent Arm & 46 Med Therapy \[MT\] Arm).Of 112, 111 met criteria & in analysis pop (58 Stent Arm & 53 MT Arm).During course of the study,of 59 randomized to Stent Arm,4 treated w/MT Only & 1 failed to meet eligibility & excluded, & of 53 randomized to MT Arm, 9 treated w/Stent+MT.
Participants by arm
| Arm | Count |
|---|---|
| Stent Group Medical therapy + PHAROS Vitesse neurovascular stent (Stent Group)
Pharos Vitesse Neurovascular Stent System (Stent implantation): Implantation of one or more balloon-expandable Pharos Vitesse stents to treat neurovascular ischemic lesions. | 58 |
| Medical Therapy Group Medical therapy alone (Medical Therapy Group)
Aspirin and Clopidogrel (Medical therapy): Treatment with aspirin (81-325 mg daily for the duration of the study) and Clopidogrel (75 mg daily for first 3 months) | 53 |
| Total | 111 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 4 | 2 |
| Overall Study | Lost to Follow-up | 6 | 10 |
Baseline characteristics
| Characteristic | Stent Group | Total | Medical Therapy Group |
|---|---|---|---|
| Age, Continuous | 61.8 years STANDARD_DEVIATION 12.3 | 61.8 years STANDARD_DEVIATION 12.5 | 61.8 years STANDARD_DEVIATION 12.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 7 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 53 Participants | 104 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 7 Participants | 14 Participants | 7 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 9 Participants | 5 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 5 Participants | 8 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 42 Participants | 80 Participants | 38 Participants |
| Region of Enrollment Austria | 4 participants | 8 participants | 4 participants |
| Region of Enrollment China | 7 participants | 14 participants | 7 participants |
| Region of Enrollment United States | 47 participants | 89 participants | 42 participants |
| Sex: Female, Male Female | 17 Participants | 38 Participants | 21 Participants |
| Sex: Female, Male Male | 41 Participants | 73 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 37 / 58 | 34 / 53 |
| serious Total, serious adverse events | 30 / 58 | 20 / 53 |
Outcome results
Primary
Successful Outcome: No Stroke or Hard TIA in the Same Territory Within 12 Months
The primary effectiveness endpoint was a composite of the two following outcomes: * Stroke in the same territory (distal to the target lesion) as the presenting event within 12 months of randomization * Hard Transient Ischemic Attack (TIA) in the same territory (distal to the target lesion) as the presenting event from day 2 through month 12 post-randomization A subject was deemed to be a primary endpoint success if neither of these outcomes occurred. The Kaplan-Meier success rate at 12-months post-operatively was calculated with Kaplan-Meier time-to-event methodology, where the time variable for patients who were successful (no stroke within 12 months or hard TIA between 2 days and 12 months) was censored at the time of last follow-up, and the time variable for patients who were not successful (had a stroke within 12 months or hard TIA between 2 days and 12 months) was censored at the time of the first event (stroke with 12 months or hard TIA between 2 days and 12 months).
Time frame: One Year
Population: Analyses were based on an intent-to-treat (ITT) population, defined as enrolled subjects who met the inclusion/exclusion criteria and who were randomized post angiogram. Stent and Medical Therapy Group subjects were analyzed according to their ITT randomized group regardless of treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stent Group | Successful Outcome: No Stroke or Hard TIA in the Same Territory Within 12 Months | 62.24 percent probability |
| Medical Therapy Group | Successful Outcome: No Stroke or Hard TIA in the Same Territory Within 12 Months | 83.68 percent probability |