Helping Stroke Patients With ThermoSuit Cooling

Study Overview
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Brief Summary
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The aim of this study is to assess the feasibility of using the Life Recovery Systems ThermoSuit Device to induce therapeutic hypothermia (32-34°C) in victims of ischemic stroke. This feasibility clinical study will enroll a total of 30 patients with acute ischemic stroke at four clinical centers. Subjects will receive hypothermia plus conventional therapy (such as IV-tPA and/or neurothrombectomy therapies if indicated). Endpoints will include feasibility of cooling, adverse events, and neurological recovery in comparison with matched historical controls.

Detailed Description
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Patients presenting to the emergency department with clinical signs and symptoms of acute ischemic stroke will undergo initial evaluation. The patient will be screened for study eligibility. A medical history and list of active medications will be documented. A physical will be conducted including the patient's temperature, hemodynamic and neurological status (NIHSS score), 12-lead ECG, and routine baseline laboratory values including magnesium, CBC, BMP, coagulation parameters, CK, CK-MB, and Troponin I. If all inclusion criteria and no exclusion criteria are present, a member of the research team will consult the patient's attending physician for permission to approach the patient. If he/she agrees, a member of the team will inform the patient or guardian about the study's purpose and obtain written informed consent. A screening log will be kept of all patients screened for this study and the reasons they were not enrolled. Prior to initiating hypothermia, Magnesium Sulfate will be administered intravenously to control shivering and tPA administered intravenously (if indicated). Induction doses of propofol or etomidate will be used to aid in the suppression of patient discomfort. Hypothermia will generally be initiated in the ED or ICU, as soon as possible after the informed consent has been obtained. However, in cases in which neurothrombectomy is indicated and judged by the investigators to be feasible to start within 90 minutes of enrollment, cooling will be delayed until its completion, and shall afterward be initiated as soon as possible. In all cases the patient will be placed in the LRS ThermoSuit in the supine position. Cooling will be started as specified in the Operator's Manual for the ThermoSuit device. Core temperature will be measured and monitored through a nasopharyngeal or esophageal temperature probe. Cooling will be initiated by circulating ice-cold water (0-8°C ± 2.0°C) through the ThermoSuit, and the start time will be recorded. Patient core and TSS water temperatures will be electronically recorded. The patient will be cooled until the core temperature reaches between 32°C to 34°C. This will require approximately 5 to 20 minutes of cooling by the ThermoSuit device (not expected to be more than 30 minutes). Arterial blood pressure and heart rate will be recorded every 5 minutes from the baseline just before the start of cooling until 30 minutes after the cooling has started. The clinician will be prompted by the automated monitor to purge the fluid from the suit when the patient's core temperature reaches approximately 33.5°C. The purging will take approximately 2 minutes. Start and stop times of purging will be recorded. The patient's body temperature should continue to decrease and then stabilize within the target range. The time at which the core temperature reaches 34°C will be recorded. The patient will be removed from the ThermoSuit immediately after water finishes draining from the suit. The time of removal will be recorded. Sedatives and analgesics will be administered for patient comfort as needed. Whether or not shivering occurs during cooling will be recorded, as well as start and stop times. Body temperature will be maintained in the range of 32°C to 34°C for a period of 24 hours following the cooling induction using a cooling blanket system. After 24 hours of therapeutic hypothermia, the patient will be re-warmed with the cooling/warming blanket until core body temperature reaches 36.5°C. This is anticipated to take approximately 8 hours. All patients will be admitted to the intensive care unit for close monitoring of physiological parameters: blood pressure, heart rate and rhythm, arterial oxygen saturation, potassium level, acid-base balance, and indicators of infection. A head CT will be performed upon admission and 24-48 hours later. Neurological status over the first 24 hours will be closely monitored and accompanied by additional brain imaging if changes in the neurological status occur. In ICU level patients, neurological status will be evaluated q1hr with the mini-NIHSS (items 1a, 1b, 1c, and motor scores for each limb), Glasgow Coma Scale, and pupillary light response. In the case of deterioration, repeat imaging which will include CT or MRI will be performed within 48 hours to compare to admission studies. Blood pressure, heart rate and rhythm, cell count, electrolytes, magnesium, coagulation profile, cardiac enzymes, liver enzymes and serum amylase will be monitored. All neurological, cardiovascular, respiratory, digestive, hematological, and metabolic complications will be recorded and treated accordingly. Intubated patients (if any) will be extubated upon rewarming if their neurological status allows for safe extubation. NIHSS will be recorded daily, and prior to discharge. Follow-Up on Day 5-7 post-treatment or at discharge (whichever comes first) Records to be collected at this time will include those related to physical exam, patient temperature, hematology, clinical chemistry, ECG, blood pressure, heart rate, concomitant medications, results of any follow-up CT or MRI scans, NIHSS, Glasgow Coma Scale, pupillary light response, MRS, Quality of Life (Neuro-QOL), and any adverse events. 3 Month Follow Up NIHSS, MRS, and Quality of Life (Neuro-QOL) will be calculated at 90 days (+/-10 days) post-stroke. Any additional adverse events will also be recorded at this time.

Official Title
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Helping Stroke Patients With ThermoSuit Cooling

Conditions
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Stroke, Brain Ischemia

Intervention / Treatment
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* Device: ThermoSuit Cooling Induction
* Drug: Magnesium Sulfate
* Drug: tPA
* Drug: Propofol
* Drug: Etomidate
* Procedure: Neurothrombectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ischemic cortical stroke with NIHSS > _5_; Treatment must be initiated within 8 hours from known time of symptom onset or, for eligible patients under the current AHA Guidelines, within the extended time window for mechanical thrombectomy of up to 24 hours. Patient dimension criteria: Height: 147-190 cm (58 - 75 in) Width: ≤66 cm (26 in) (elbow to elbow). Exclusion Criteria: Sepsis (bacteremia and clinical syndrome within 72 h); Known preexisting coagulopathy, (INR > 1.3, PTT >1.5 x control), active bleeding of unknown cause, immune compromised state, thrombocytopenia (platelet count < 160,000/mm), and history of cold agglutinin disease; Hemodynamically significant cardiac dysrhythmias (eg. QTc interval >450 msec, bradycardia (heart rate less than 50), Mobitz Type II second degree AV block (or higher AV block), and severe ventricular dysrhythmias (sustained VT or VF) ) which cause significant hypotension (SBP ≤ 120 mmHg requiring more than two pressor medications); Preexistent illness with life expectancy <6 months; Pregnancy; Rapidly improving symptoms; Melena, or gross hematuria; Sickle cell disease; Temperature < 35°C on admission to Emergency Department; Recent (< 1 week) incisions; Any intracerebral hemorrhage; A history of a brain vascular lesion (e.G. aneurism or arteriovenous malformation); A history of brain disease or damage (e.g. neoplasm or dementia); Patients receiving IV tPA > 3 hours from stroke onset; Bradycardia (heart rate ≤ 50); High degree AV block; Ventricular tachycardia; Ventricular fibrillation. Significant hypotension < 120 mm Hg, regardless of the underlying cause Exclusions for Patients to receive IV tPA : Suspicion of subarachnoid hemorrhage on pretreatment evaluation, even with normal neuroimaging; Systolic blood pressure greater than 185 mm of Hg or diastolic blood pressure >110 mmHg at the time of t-PA infusion and/or patient requires aggressive treatment to reduce blood pressure to within these limits; Seizure at onset of stroke; Active internal bleeding; Known bleeding diathesis, including but not limited to: Platelet count less than 100,000/mm3 Heparin during the preceding 48 hours and elevated aPTT (greater than upper limit of normal for laboratory) Current use of oral anticoagulants (ex: warfarin) and INR >1.7; Current use of direct thrombin inhibitors or direct factor Xa inhibitors Elevated prothrombin time (PT) greater than 15 seconds. Major surgery or other serious trauma during preceding 14 days; Intercranial or intraspinal surgery, stroke, serious head trauma during preceding 3 months; Recent arterial puncture at a non-compressible site; Recent lumbar puncture during preceding 7 days; History of intracranial hemorrhage, neoplasm, arteriovenous malformation, or aneurysm; Recent Acute Myocardial Infarction Abnormal blood glucose (<50 or >400 mg/dL) Suspected/confirmed endocarditis Exclusions for Patients Receiving Neurothrombectomy > Patients with known hypersensitivity to nickel-titanium Patients with stenosis and/or pre-existing stent proximal to the thrombus site that may preclude safe recovery of the revascularization device Patients with angiographic evidence of carotid dissection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ThermoSuit Cooling Induction<br>Induction of therapeutic hypothermia (32-34 degrees C) using the LRS ThermoSuit System. Prior to initiating hypothermia, Magnesium Sulfate will be administered intravenously to control shivering and tPA administered intravenously (if indicated). Induction doses of propofol or etomidate will be used to aid in the suppression of patient discomfort. Neurothrombectomy will be performed if indicated. | Device: ThermoSuit Cooling Induction<br>* Rapid induction of therapeutic hypothermia (32-34 degrees C) using the Life Recovery Systems ThermoSuit System<br>* Other names: LRS ThermoSuit;Drug: Magnesium Sulfate<br>* Magnesium sulfate will be administered intravenously as needed to control shivering<br>* Other names: Magnesium sulphate;Drug: tPA<br>* tPA will be administered intravenously if indicated<br>* Other names: Tissue plasminogen activator;Drug: Propofol<br>* Induction doses of propofol or etomidate will be used to aid in the suppression of patient discomfort<br>* Other names: Diprivan;Drug: Etomidate<br>* Induction doses of propofol or etomidate will be used to aid in the suppression of patient discomfort<br>* Other names: Amidate;Procedure: Neurothrombectomy<br>* If indicated, neurothrombectomy will be performed using an FDA-cleared device within the FDA-cleared treatment window.<br>* Other names: Endovascular Thrombectomy;|
| No Intervention: Historical Control<br>Historical patients treated for ischemic stroke using conventional medical treatments, but without induced hypothermia. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of cooling as indicated by percentage of patients cooled to target within 1 hour of start of cooling | Feasibility of rapidly cooling victims of ischemic stroke with the ThermoSuit System to 32-34°C. | 1 hour after start of cooling | 
| Neurological outcome as indicated by NIHSS | NIH Stroke Scale at hospital discharge or day 5-7 post-treatment (whichever comes first) | Hospital discharge or day 5-7 post-treatment (whichever comes first) | 
| Safety of the cooling treatment as indicated by rates of significant adverse events | A comparison of significant adverse event rates between the treatment and historical control group. | 30 days | 
| Neurological outcome as indicated by MRS score | Dichotomized modified Rankin score (mRS); an mRS score of less than or equal to 2 is to be considered a good outcome | Hospital discharge or day 5-7 post-treatment (whichever comes first) | 
| Change in neurological outcome as indicated by NIHSS | Change in NIHSS from that measured at hospital discharge or 5-7 days post-treatment (whichever comes first) to that measured at 90 +/- 10 days post-stroke | Hospital discharge or 5-7 days post-treatment (whichever comes first) and 90 +/- 10 days post-stroke | 
| Change in neurological status as indicated by MRS | Change in dichotomized modified Rankin scale from that measured at hospital discharge or 5-7 days post-treatment (whichever comes first) to that measured at 90 +/- 10 days post-stroke | Hospital discharge or 5-7 days post-treatment (whichever comes first) and 90 +/- 10 days post-stroke | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Patient death within 90 days | 90 days | 
| Quality of Life as indicated by Neuro-QOL score | Quality of Life of treated patients as assessed using Neuro-QOL forms. | Hospital discharge or 5-7 days post-treatment (whichever comes first) and 90 +/- 10 days post stroke | 
| Rates of procedure and device related SAEs | Analysis of all procedure and device related significant adverse events | 0 to 90 days |