A Multicenter, Randomized, Double Blind, Sham Controlled Trial to Assess the Efficacy of the Ischemic Stroke System (ISS) in Preventing Progressive Reduction of Salvageable Brain Tissue Volume in Subjects With Acute Ischemic Stroke
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Ischemic Stroke
- Sponsor
- BrainsGate
- Enrollment
- 100
- Locations
- 4
- Primary Endpoint
- Volume of core expansion
- Last Updated
- 6 years ago
Overview
Brief Summary
The primary objective of the study is to demonstrate that SPG (Sphenopalatine Ganglion) stimulation started within 6 hours from stroke onset slows the expansion of the infarct core volume in acute ischemic stroke.
Detailed Description
The goal of this study is to identify Acute Ischemic Stroke patients who have a potentially salvageable penumbra and to test if 6 hours of SPG (Sphenopalatine Ganglion) stimulation may "freeze" the volume of the penumbra and reduce the extent of tissue death. Following a minimally-invasive implantation of the ISS injectable implant, patients will be randomized to either the Treated or Control arm in a 1:1 ratio. Randomization will be dynamic according to the patient's baseline covariates of core volume, total volume, Hypoperfusion Intensity Ratio (HIR), time to baseline imaging, age, NIHSS. Patients in the Treated arm will be treated with active SPG stimulation while patients in the Control arm will undergo sham treatment. After treatment/sham treatment, patients in both groups will undergo a follow up brain non-contrast CT, CT perfusion and CT angiography imaging, 6:45hrs±15min after baseline CTP initiation. In the case the patient is cooperative, hand strength (pinch and grasp) evaluations should be assessed before and during the 1st treatment/ sham SPG stimulation session. Following the assessment of the penumbra (after 6 hours) patients will be treated or sham treated for 5 additional consecutive sessions (4 hours each), the first starting within 18-24 hours from stroke onset and the others 18-26 hours from previous treatment initiation and will be followed for 90 days to assess their clinical outcome. In one session (preferably at day 2) Common Carotid Doppler examination is performed to evaluate blood flow dynamics before and during the treatment/sham session. After the last treatment session, the implant is removed.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signs \& symptoms consistent with the diagnosis of large vessel occlusion in the anterior circulation
- •Age 18-90 years
- •Baseline NIHSS ≥ 10
- •Ability to initiate treatment within 6 hours from stroke onset. Stroke onset is defined as the time the patient was last seen well.
- •Large vessel total occlusion by CTA
- •Penumbra ≥ 50ml (Difference between Tmax6 volume and the ischemic core volume (CBF\<38% volume)
- •Mismatch (Tmax6 volume/ischemic core volume (CBF\<38% volume) ≥1.5
- •Core and HIR (Tmax10 / Tmax6) volumes:
- •HIR ≥ 0.5 or
- •0.35 ≤ HIR \< 0.5 and "core volume/time from onset to imaging" ≥ 7mililiter/hour
Exclusion Criteria
- •Unable to undergo a contrast brain perfusion scan, including an allergy to contrast media
- •Opportunity for reperfusion therapy (IV thrombolysis or endovascular treatment)
- •Neuro-imaging evidence of any intracranial hemorrhage or hemorrhagic transformation of brain infarct or other significant abnormality (e.g. tumor, abscess, suspect for subarachnoid hemorrhage, arteriovenous malformation, cerebral aneurysm).
- •Significant mass effect with midline shift.
- •Infarct core volume \>150 milliliter
- •Old non-lacunar infarct in the anterior circulation on the ipsilateral hemisphere.
- •Previous stroke in the last 6 months or previous stroke with existing sequelae or with mRS \> 0 for any reason
- •Pre-existing Modified Rankin Score \>1, even if not stroke-related.
- •Acute symptomatic arterial occlusions in more than one vascular territory confirmed on CTA/MRA (e.g., bilateral MCA occlusions, or an MCA and a basilar artery occlusion).
- •Seizures at stroke onset
Outcomes
Primary Outcomes
Volume of core expansion
Time Frame: Day 1
The primary outcome measure is the volume of core expansion (in milliliters) in 6:45h±15 min. Core expansion is the difference of two volumes: Core volume (CBF\<38%) in follow up CTP (at 6:45h±15 min) and Core volume (CBF\<38%) in baseline CTP. The difference in the mean core expansion between the Treated and Control groups will be assessed as a continuous variable with adjustment for baseline covariates (Core volume, Total volume, HIR, Time to baseline imaging). The two-sided significance level is 0.05. Handling of missing data in the primary analysis: Patients who die before the 6:45h±15 min follow-up imaging will be assigned a final core volume that equal the baseline total volume. Patients with non-interpretable follow-up imaging will be excluded from the analysis.
Secondary Outcomes
- Difference in infarct volume between baseline CTP core volume and follow up NCCT infarct volume.(Day 1)
- Difference in infarct volume between baseline CTP core volume and Day-5 NCCT infarct volume(Day 5)
- 3 months mRS(Day 90±7)
- Increased blood flow in Common Carotid Doppler(Day 2-6)
- Improvement in hand motor performance(Day 1)