Acute Ischemic Stroke
Conditions
Keywords
Ischemic Stroke, Brain cooling, Cerebral Hypothermia, Neuroprotection, Mechanical Thrombectomy
Brief summary
Reducing the temperature of tissue or organs (hypothermia) produces a protective state, through multiple molecular mechanisms, against adverse effects that arise from disrupted organ blood flow, e.g. in acute ischemic stroke (AIS). AIS is often caused by a blood clot that occludes a brain artery which, in turn disrupts brain blood flow. In large vessel occlusions, the current standard includes mechanical thrombectomy (MT), a minimally-invasive procedure that aims at removing the clot via endovascular means. In this case, brain cooling can lead to protection (neuroprotection) not only from the adverse effects of stroke/ischemia itself, but also from complications arising from sudden re-opening of the blocked artery through primary treatment, MT. This potential complication of MT is called reperfusion injury. In this first-in-human investigational deivce study, Hybernia Medical's endovascular brain cooling system will be applied in acute ischemic stroke patients undergoing MT. Post-MT, selective brain hypothermia will be induced and maintained over 30 minutes. Endpoints of this study include, clinical safety, device performance/usability, and clinical outcome.
Interventions
DEVICEBrain cooling
Brain cooling intervention in acute ischemic stroke patients post mechanical thrombectomy
Sponsors
Hybernia Medical
Hospital Universitari Vall d'Hebron Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DEVICE_FEASIBILITY
Masking
NONE
Intervention model description
Fist-in-human investigational device study
Eligibility
Sex/Gender
ALL
Age
18 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18 to 89 2. Informed signed consent obtained from patient or legally authorized representative 3. Clinical symptoms consistent with acute ischemic stroke 4. Pre-stroke modified Rankin Scale (mRS) score 0-1 5. National Institute of Health Stroke Scale (NIHSS) ≥ 6 6. Alberta Stroke Program Early CT Score (ASPECTS) score 5-10 7. IV tissue plasminogen activator (tPA) or Tenecteplase (TNK) may be administered within 4.5h of last known well (LKW), if patient eligible 8. Mechanical thrombectomy (MT) treatment performed with arterial puncture within 24h of LKW. 9. Pre-MT catheter angiogram shows target occlusion in intracranial ICA, M1 MCA, or M2 MCA 10. End of MT catheter angiogram shows achievement of moderate-to-complete reperfusion (modified Treatment in Cerebral Ischemia score or mTICI 2a-3)
Exclusion criteria
1. Pre-MT CT or MRI shows acute intracranial hemorrhage. 2. Previous intracranial hemorrhage, AVM, neoplasm (except small meningioma), or vascular stent-implant 3. Coma or reduced level of consciousness prior to MT (NIHSS 1A\>1) 4. Seizure between LKW and time of potential enrollment 5. Severe contrast allergy or absolute contraindication to iodinated contrast. 6. Hypersensitivity to cold, i.e., history of cold-sensitive antibodies, Raynaud syndrome, or hepatitis C 7. Hematocrit \<33% 8. Severe known renal impairment, i.e., requires renal replacement therapy (dialysis). 9. Post-reperfusion investigational therapy cannot be started within 150 min following pre-treatment CT or MR imaging 10. Presumed septic embolism, suspicion of bacterial endocarditis. 11. Known pregnancy (in women with child-bearing potential) 12. Body weight \< 40kg 13. Patient not willing and able to participate in follow-up visits to day 90. 14. Life expectancy \<6 months due to pre-existing conditions such as severe heart or renal failure, cancer, etc. 15. Currently or within past 30 days participating in another investigational treatment study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Device Feasibility | During the intervention | Completion of Brain Cooling over 30 minutes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Any Intracranial Hemorrhage | Up to 7 days after the intervention | Any radiologic confirmed intracranial hemorrhage as detected on follow-up CT. |
| Symptomatic Intracranial Hemorrhage | Up to 7 days after the intervention | Associated with NIHSS reduction of ≥4 points or death |
| Serious Adverse Events | Up to 7 days after the intervention | Incidence of serious adverse device effect (SADE) |
| Hypothermia Effect on Vasculature | Up to 24 hours after the intervention | Hypothermia effect on vasculature, such as vasospasm on cerebral angiogram or follow-up CTA |
| Mortality | Up to 3 months after the intervention | Death |
| Hospital Readmission | Up to 3 months after the intervention | Due to stroke |
| Device Performance and Usability | During the intervention | * Device installation, setup, and use * Circuit performance * Cooling performance and accuracy * Correct trigger of alarms |
| Final modified Treatment in Cerebral Infarction (mTICI) score | Pre-intervention | Grade 0: no perfusion Grade 1: antegrade reperfusion past the initial occlusion, but limited distal branch filling with little or slow distal reperfusion Grade 2 Grade 2a: antegrade reperfusion of less than half of the occluded target artery previously ischemic territory (e.g. in one major division of the middle cerebral artery (MCA) and its territory) Grade 2b: antegrade reperfusion of more than half of the previously occluded target artery ischemic territory (e.g. in two major divisions of the MCA and their territories) Grade 2c: near complete perfusion except for slow flow or distal emboli in a few distal cortical vessels Grade 3: complete antegrade reperfusion of the previously occluded target artery ischemic territory, with absence of visualized occlusion in all distal branches |
| Infarct Size | 3 days after the intervention and up to 7 days after the intervention | Final infarct size/volume |
| Global Disability via modified Rankin Scale (mRS) | Month 1 and Month 3 after the intervention | mRS is a scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke. (0) No symptoms at all 1. No significant disability despite symptoms; able to carry out all usual duties and activities 2. Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance 3. Moderate disability; requiring some help, but able to walk without assistance 4. Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance 5. Severe disability; bedridden, incontinent and requiring constant nursing care and attention 6. Dead |
Countries
Spain
Contacts
PRINCIPAL_INVESTIGATORMarc Ribo, MD, PhD
Vall d'Hebron University Hospital
Outcome results
None listed