Clinical trial NCT02453373: Helping Stroke Patients With ThermoSuit Cooling
Official title: Helping Stroke Patients With ThermoSuit Cooling
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Stroke
Brain Ischemia
Lead sponsor: Life Recovery Systems
Sponsor class: OTHER
Collaborators: name: Tulane University School of Medicine
name: Geisinger Clinic
First posted: 2015-05-25
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Feasibility of cooling as indicated by percentage of patients cooled to target within 1 hour of start of cooling
timeFrame: 1 hour after start of cooling
measure: Neurological outcome as indicated by NIHSS
timeFrame: Hospital discharge or day 5-7 post-treatment (whichever comes first)
measure: Safety of the cooling treatment as indicated by rates of significant adverse events
timeFrame: 30 days
measure: Neurological outcome as indicated by MRS score
timeFrame: Hospital discharge or day 5-7 post-treatment (whichever comes first)
measure: Change in neurological outcome as indicated by NIHSS
timeFrame: Hospital discharge or 5-7 days post-treatment (whichever comes first) and 90 +/- 10 days post-stroke
measure: Change in neurological status as indicated by MRS
timeFrame: Hospital discharge or 5-7 days post-treatment (whichever comes first) and 90 +/- 10 days post-stroke
Secondary outcomes:
measure: Mortality
timeFrame: 90 days
measure: Quality of Life as indicated by Neuro-QOL score
timeFrame: Hospital discharge or 5-7 days post-treatment (whichever comes first) and 90 +/- 10 days post stroke
measure: Rates of procedure and device related SAEs
timeFrame: 0 to 90 days
Other outcomes:
Locations:
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Geisinger Wyoming Valley Medical Center
state: Pennsylvania
city: Columbia
country: United States
facility: U of SC School of Medicine
state: South Carolina
Study officials:
affiliation: Tulane University
name: Aimee Aysenne, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL; American Heart Association Stroke Council. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2018 Mar;49(3):e46-e110. doi: 10.1161/STR.0000000000000158. Epub 2018 Jan 24.