Hypothermia in Acute Ischemic Stroke - Surface Versus Endovascular Cooling (HAIS-SE)

Study Overview
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Brief Summary
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HAIS-SE is evaluating for the first time ever in a randomized controlled trial efficacy, tolerability, practicability and safety of endovascular versus surface cooling in awake stroke patients.

Detailed Description
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Mild hypothermia improves outcome in patients with global cerebral ischemia after cardiac arrest. Via animal models hypothermia has been identified as the most promising neuroprotective therapy in focal cerebral ischemia as well. But the prove of clinical benefit in patients with acute ischemic stroke is still missing: Most likely due to the prolonged time window until hypothermia-induction (14 h) in previous studies. In addition, feasibility of the method through which hypothermia is applied is crucial for a broad implementation of hypothermia in stroke therapy. Surface versus endovascular cooling have never been compared in a prospective trial in awake stroke patients. HAIS-SE is evaluating for the first time ever in a randomized controlled trial efficacy, tolerability, practicability and safety of endovascular versus surface cooling in awake stroke patients.

Official Title
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HAIS-SE (Hypothermia in Acute Ischemic Stroke - Surface Versus Endovascular Cooling): A Randomized Trial Comparing Surface Versus Endovascular Cooling in Awake Stroke Patients Treated With Thrombolysis

Conditions
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Ischemic Stroke, Thrombolysis, Hypothermia

Intervention / Treatment
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* Device: ZOLL Thermogard XP
* Device: BARD/Medivance Arctic Sun 5000


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ischemic stroke Intravenous thrombolysis within 4.5h from symptom onset Informed consent of the patient NIHSS score ≥ 2 and ≤ 20 Age ≥ 18 and ≤ 90 years Placement of cooling catheter / cooling pads within 6h from symptom onset Exclusion Criteria: (Expected) intubation (e.g. for interventional treatment) Pregnancy Body weight > 120kg Body height < 150cm Life-expectancy < 3 months Fever > 38.5°C at screening Known hematologic disease with increased risk of thrombosis (e.g. cryoglobulinemia, cold agglutinins, sickle cell anemia) Known vasospastic vascular disorder (e.g. Raynaud's phenomenon or thromboangiitis obliterans) Possible compression of the inferior vena cava (e.g. due to tumor) or vena cava filter Acute pulmonary embolism Acute myocardial infarction Severe cardiac insufficiency (NYHA ≥ III) Threatening ventricular dysrhythmia QTc-interval > 450ms Bradycardia < 50/min Sick-Sinus-Syndrom AV-block > I° Severe infection with bacteremia or sepsis ≤ 72h Severe renal (GFR < 30ml/min) or liver insufficiency (Child-Pugh C) Myopathy Known intolerance or allergy against acetaminophen, buspirone, clonidine, magnesium sulphate or pethidine. Treatment with MAO-inhibitors ≤ 14 days Acute closed-angle glaucoma

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Endovascular cooling<br>Endovascular cooling using the cooling device ZOLL Thermogard XP with ZOLL Quattro cooling catheter | Device: ZOLL Thermogard XP<br>* Induction of hypothermia with 1L cold crystalloid infusions (0,9%NaCl or Ringer's solution). Cooling catheter placement at the earliest 30min after end of thrombolysis.<br>* Other names: ZOLL Quattro cooling catheter, ZOLL Circulation, Inc., USA;|
| Active Comparator: Surface cooling<br>Surface cooling using the cooling device BARD/Medivance Arctic Sun 5000 with BARD/Medivance Arctic Gel Pads | Device: BARD/Medivance Arctic Sun 5000<br>* Induction of hypothermia with 1L cold crystalloid infusions (0,9%NaCl or Ringer's solution) and simultaneous start of surface cooling.<br>* Other names: BARD/Medivance Arctic Gel Pads, C. R. Bard, Inc., USA;|
| No Intervention: Control group<br>Best medical treatment following international stroke guidelines | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body core temperature | Primary endpoint: Time to primary target body core temperature (34°C) after hypothermia-induction. | 0 to 48h | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy | Secondary efficacy outcome measures include the amount of patients reaching the primary target body core temperature (34°C), the time-frame until reaching 35°C body core temperature, temperature stability during maintenance and rewarming. | 0 to 48h | 
| Tolerability | Tolerability outcome measures include a specific Hypothermia Participant Experience Questionnaire (HPEQ) and the Bedside Shivering Assessment Scale (BSAS) plus correlation with skin temperature, EMG and sNIRS. | 0 to 48h | 
| Practicability | Practicability outcome measures include a specific Hypothermia Nursing Staff Experience Questionnaire (HNEQ). | 0 to 48h | 
| Safety | Safety outcome measures include the analysis of (severe) adverse events (e.g. bleeding complications, pneumonia). 0 to 48h: Dose needed of anti-shivering medication, level of sedation (RASS, GCS and BIS), safety laboratory including specific coagulation parameters and monitoring of cerebral auto-regulation including cNIRS and BIS. | 0 to d90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypothermia, induction of hypothermia, non invasive cooling, external cooling, surface cooling, endovascular cooling, cooling catheter, stroke, shivering, neuro monitoring, coagulation