Helping Stroke Patients With ThermoSuit Cooling

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.

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