Clinical trial NCT06634303: Hybernia Medical Post-Mechanical Thrombectomy Cerebral Cooling in Stroke
Official title: Hybernia Delta H (ΔH) Brain Cooling System for: Post-Mechanical Endovascular Cerebral Cooling
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Acute Ischemic Stroke
Keywords: Ischemic Stroke
Brain cooling
Cerebral Hypothermia
Neuroprotection
Mechanical Thrombectomy
Lead sponsor: Hybernia Medical
Sponsor class: INDUSTRY
Collaborators: name: Hospital Universitari Vall d'Hebron Research Institute
First posted: 2024-10-09
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Fist-in-human investigational device study
Primary purpose: DEVICE_FEASIBILITY

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.


Eligibility criteria: 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

Primary outcomes:
measure: Device Feasibility
timeFrame: During the intervention
Secondary outcomes:
measure: Any Intracranial Hemorrhage
timeFrame: Up to 7 days after the intervention
measure: Symptomatic Intracranial Hemorrhage
timeFrame: Up to 7 days after the intervention
measure: Serious Adverse Events
timeFrame: Up to 7 days after the intervention
measure: Hypothermia Effect on Vasculature
timeFrame: Up to 24 hours after the intervention
measure: Mortality
timeFrame: Up to 3 months after the intervention
measure: Hospital Readmission
timeFrame: Up to 3 months after the intervention
measure: Device Performance and Usability
timeFrame: During the intervention
measure: Final modified Treatment in Cerebral Infarction (mTICI) score
timeFrame: Pre-intervention
measure: Infarct Size
timeFrame: 3 days after the intervention and up to 7 days after the intervention
measure: Global Disability via modified Rankin Scale (mRS)
timeFrame: Month 1 and Month 3 after the intervention
Other outcomes:
measure: Time to Reperfusion
timeFrame: Pre-intervention
measure: Reperfusion Time
timeFrame: Pre-intervention
Locations:
city: Barcelona
country: Spain
facility: Vall d'Hebron University Hospital
Study officials:
affiliation: Vall d'Hebron University Hospital
name: Marc Ribo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mangla S, Choi JH, Barone FC, Novotney C, Libien J, Lin E, Pile-Spellman J. Endovascular external carotid artery occlusion for brain selective targeting: a cerebrovascular swine model. BMC Res Notes. 2015 Dec 21;8:808. doi: 10.1186/s13104-015-1714-7.
citation: Dumitrascu OM, Lamb J, Lyden PD. Still cooling after all these years: Meta-analysis of pre-clinical trials of therapeutic hypothermia for acute ischemic stroke. J Cereb Blood Flow Metab. 2016 Jul;36(7):1157-64. doi: 10.1177/0271678X16645112. Epub 2016 Apr 18.
citation: Wu C, Zhao W, An H, Wu L, Chen J, Hussain M, Ding Y, Li C, Wei W, Duan J, Wang C, Yang Q, Wu D, Liu L, Ji X. Safety, feasibility, and potential efficacy of intraarterial selective cooling infusion for stroke patients treated with mechanical thrombectomy. J Cereb Blood Flow Metab. 2018 Dec;38(12):2251-2260. doi: 10.1177/0271678X18790139. Epub 2018 Jul 18.
citation: Wan Y, Tian H, Wang H, Wang D, Jiang H, Fang Q. Selective intraarterial hypothermia combined with mechanical thrombectomy for acute cerebral infarction based on microcatheter technology: A single-center, randomized, single-blind controlled study. Front Neurol. 2023 Feb 16;14:1039816. doi: 10.3389/fneur.2023.1039816. eCollection 2023.
citation: Neimark MA, Konstas AA, Lee L, Laine AF, Pile-Spellman J, Choi J. Brain temperature changes during selective cooling with endovascular intracarotid cold saline infusion: simulation using human data fitted with an integrated mathematical model. J Neurointerv Surg. 2013 Mar;5(2):165-71. doi: 10.1136/neurintsurg-2011-010150. Epub 2012 Jan 22.
citation: Choi JH, Pile-Spellman J. Reperfusion Changes After Stroke and Practical Approaches for Neuroprotection. Neuroimaging Clin N Am. 2018 Nov;28(4):663-682. doi: 10.1016/j.nic.2018.06.008.
citation: Choi JH, Pile-Spellman J. Selective brain hypothermia. Handb Clin Neurol. 2018;157:839-852. doi: 10.1016/B978-0-444-64074-1.00052-5.
citation: Choi JH, Poli S, Chen M, Nguyen TN, Saver JL, Matouk C, Pile-Spellman J. Selective Brain Hypothermia in Acute Ischemic Stroke: Reperfusion Without Reperfusion Injury. Front Neurol. 2020 Nov 13;11:594289. doi: 10.3389/fneur.2020.594289. eCollection 2020.
citation: Konstas AA, Neimark MA, Laine AF, Pile-Spellman J. A theoretical model of selective cooling using intracarotid cold saline infusion in the human brain. J Appl Physiol (1985). 2007 Apr;102(4):1329-40. doi: 10.1152/japplphysiol.00805.2006. Epub 2006 Dec 14.
citation: Choi JH, Marshall RS, Neimark MA, Konstas AA, Lin E, Chiang YT, Mast H, Rundek T, Mohr JP, Pile-Spellman J. Selective brain cooling with endovascular intracarotid infusion of cold saline: a pilot feasibility study. AJNR Am J Neuroradiol. 2010 May;31(5):928-34. doi: 10.3174/ajnr.A1961. Epub 2010 Jan 6.