Clinical trial NCT03804060: REperfusion With Cooling in CerebraL Acute IscheMia II
Official title: A Multicenter, Prospective, Randomized-controlled Trial to Assess the Safety and Feasibility of Cooling as an Adjunctive Therapy to Thrombectomy and Reperfusion in Patients With Acute Cerebral Ischemia and Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Ischemic Stroke
Keywords: Therapeutic Hypothermia
Cooling
Stroke
Neurological Acute Care
Lead sponsor: ZOLL Circulation, Inc., USA
Sponsor class: INDUSTRY
First posted: 2019-01-15
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to determine the feasibility and safety of achieving rapid hypothermia with the Proteus Intravascular Temperature Management (IVTM) system for patients experiencing acute ischemic stroke due to a large vessel occlusion.


Eligibility criteria: All Inclusion Criteria must be answered YES for Patient to be eligible.

1. Age ≥18 and ≤85;
2. Signs and symptoms consistent with an acute ischemic stroke with anterior circulation large vessel occlusion (M1 MCA, carotid-terminus occlusion, Tandem occlusion allowed (Extracranial ICA+carotid T or M1 MCA)) as determined by CT imaging; (i.e., hyperdense sign on non-contrast CT or CT angiogram);
3. Ability to perform arterial puncture within 24 hours from symptom onset or LKN;
4. ASPECTS score of 6-10 on non-contrast CT of the brain if under 80 years; ASPECTS 9-10 if age 80-85;
5. For transfer patients with anticipated arterial puncture greater than 6 hours from symptom onset or LKN, qualifying imaging must be performed within 2 hours prior to enrolling hospital arrival; or with a newly obtained non-contrast CT scan if this time is exceeded
6. Candidate for endovascular thrombectomy therapy in accordance with best practices per AHA standard stroke guidelines meeting all labeling requirements for EVT in the trial;
7. No contraindications to general anesthesia, conscious sedation or allergies to any components associated with the anticipated diagnostic or treatment procedures that cannot be treated;
8. A pre-stroke modified Rankin Score (mRS) of 0 or 1 (Appendix 4);
9. Baseline CT scan shows no hemorrhage;
10. NIHSS greater than or equal to 8 (Appendix 3);
11. Patient is capable of complying with study procedures and agrees to complete all required study procedures, study visits and associated activities;
12. Legally authorized representative must be able to understand and give written informed consent. Patient will assent if capable. Patient may be re-consented once it is established that there is no memory loss or cognitive impairment.

5.2 Exclusion Criteria In order to be eligible for participation, patients must meet all Inclusion and Exclusion Criteria.

Inclusion Criteria All Inclusion Criteria must be answered YES for Patient to be eligible.

1. Age ≥18 and ≤85;
2. Signs and symptoms consistent with an acute ischemic stroke with anterior circulation large vessel occlusion (M1 MCA, carotid-terminus occlusion, Tandem occlusion allowed (Extracranial ICA+carotid T or M1 MCA)) as determined by CT imaging; (i.e., hyper dense sign on non-contrast CT or CT angiogram);
3. Ability to perform arterial puncture within 24 hours from symptom onset or LKN;
4. ASPECT score of 6-10 on non-contrast CT of the brain if under 80 years; ASPECTS 9-10 if age 80-85;
5. For transfer patients with anticipated arterial puncture greater than 6 hours from symptom onset or LKN, qualifying imaging must be performed within 2 hours prior to enrolling hospital arrival or with a newly obtained non-contrast CT scan if this time is exceeded;
6. Candidate for endovascular thrombectomy therapy in accordance with best practices per AHA standard stroke guidelines meeting all labeling requirements for EVT in the trial;
7. No contraindications to general anesthesia, conscious sedation or allergies to any components associated with the anticipated diagnostic or treatment procedures that cannot be treated;
8. A pre-stroke mRS of 0 or 1 (Appendix 4);
9. Baseline CT scan shows no hemorrhage;
10. NIHSS greater than or equal to 8 (Appendix 3);
11. Patient is capable of complying with study procedures and agrees to complete all required study procedures, study visits and associated activities;
12. Legally authorized representative must be able to understand and give written informed consent. Patient will assent if capable. Patient may be re-consented once it is established that there is no memory loss or cognitive impairment.

Exclusion Criteria All Exclusion Criteria must be answered NO to be eligible.

1. Patient arrives to the enrolling hospital intubated
2. Female patients of childbearing potential who are known to be or may be pregnant;
3. The patient has a known history of bleeding diathesis, coagulopathy, cryoglobulinemia, sickle cell anemia, will refuse blood transfusions or contraindication to heparin; history of genetically confirmed hypercoagulable syndrome
4. The patient has a height of \< 1.5 meters (4 feet 11 inches);
5. Use of warfarin with INR \> 1.7;
6. Blood clinical chemistry potassium (K+) \< 2.7;
7. History of severe dementia and currently taking medication for cognitive impairment or behavior disorder;
8. End stage renal disease on hemodialysis;
9. Known presence of an IVC filter;
10. Contrast dye allergy with history of anaphylaxis, known serious sensitivity to contrast agents or any condition in which angiography is contraindicated;
11. Known to have contraindications to radiological imaging;
12. Known allergy to meperidine or buspar or dexmedetomidine;
13. Sustained hypertension (SBP \> 185 or DBP \> 110 unable to be treated with a continuous infusion, e.g., nicardipine);
14. Baseline CT/MR showing evidence of arterial vasculitis or dissection;
15. Baseline CT/MR evidence of multiple vascular territory acute stroke;
16. Excessive tortuosity of cervical vessels;
17. Intracranial stent in area that may impact Recanalization;
18. Presence of Pulmonary embolism, ilio-femoral or deep vein thrombosis
19. Presence of clinical signs of sepsis
20. Ongoing or spontaneous atrial fibrillation indicating severe peripheral vascular disease, aortic disease, or proximal cerebrovascular disease that in the opinion of the investigator precludes access or safe endovascular treatment
21. Presence of any other serious comorbidity that would be likely to impact life expectancy to less than 6 months or limit Patient cooperation or study compliance
22. Concurrent participation in an investigational clinical study (excluding registries) that has not completed the follow-up period or planned participation in another study within the next 3 months;
23. Patient has any other condition(s) or circumstance(s) that, in the judgement of the investigator, might interfere with or impact the collection of high quality data, or with the completion of follow up requirements within the study windows.
24. Patient has active or symptomatic COVID-19
25. Patients without a legally authorized representative to sign the consent form will be excluded.

Primary outcomes:
measure: Percentage of Test Arm patients achieving target temperature
timeFrame: 1 hour after thrombectomy
measure: Mean door-to-Recanalization time
timeFrame: perioperative
measure: Rate of hemorrhagic conversion in each arm within 36 hours of Recanalization
timeFrame: 36 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Marietta
country: United States
facility: WellStar Kennestone Regional Medical Center
state: Georgia
city: Honolulu
country: United States
facility: The Queen's Medical Center
state: Hawaii
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Detroit
country: United States
facility: Henry Ford
state: Michigan
city: Toledo
country: United States
facility: ProMedica Toledo Hospital
state: Ohio
city: Toledo
country: United States
facility: Mercy Health
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
Study officials:
affiliation: Wellstar Medical Group
name: Rishi Gupta, MD, MBA
role: PRINCIPAL_INVESTIGATOR
References: