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

Phase 2

• Conditions: Ischemic Stroke; Thrombolysis; Hypothermia
• Interventions: Device: BARD/Medivance Arctic Sun 5000; Device: ZOLL Thermogard XP

• Registration Number: NCT01665885
• Lead Sponsor: University Hospital Heidelberg

Brief Summary

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

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.

Study Timeline

• Study Start: 2012-08
• Study First Submitted: 2012-08-13
• Study First Submitted QC: 2012-08-13
• Study First Posted: 2012-08-15
• Status Verified: 2013-06
• Last Update Submitted: 2015-02-16
• Last Update Posted: 2015-02-18
• Primary Completion: 2015-08
• Study Completion: 2015-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Surface cooling	BARD/Medivance Arctic Sun 5000	Surface cooling using the cooling device BARD/Medivance Arctic Sun 5000 with BARD/Medivance Arctic Gel Pads
Endovascular cooling	ZOLL Thermogard XP	Endovascular cooling using the cooling device ZOLL Thermogard XP with ZOLL Quattro cooling catheter

Primary Outcome Measures

Name	Time	Method
Body core temperature	0 to 48h	Primary endpoint: Time to primary target body core temperature (34°C) after hypothermia-induction.

Secondary Outcome Measures

Name	Time	Method
Efficacy	0 to 48h	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.
Tolerability	0 to 48h	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.
Practicability	0 to 48h	Practicability outcome measures include a specific Hypothermia Nursing Staff Experience Questionnaire (HNEQ).
Safety	0 to d90	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.

Trial Locations

Locations (1)

Stroke Unit, Dept. of Neurology, University Hospital Heidelberg; 🇩🇪 Heidelberg, Germany