A Randomized Trial Comparing 2 Methods for Rapid Induction of Cooling in Stroke Patients, Cold Infusions vs. EMCOOLS Flex.Pads (iCOOL 2)

Study Overview
=================
Brief Summary
-----------------
Mild hypothermia improves outcome in patients with global cerebral ischemia after cardiac arrest. Hypothermia seems promising also in other acute hypoxic-ischemic or in brain swelling associated cerebrovascular disease. The narrow-time-frame is a major issue (time is brain). To provide immediate cooling without delay, easy to use, mobile and effective methods are needed. Cold infusions (4 °C) are an accepted standard worldwide. EMCOOLS Flex.Pads (Emergency Medical Cooling Systems AG, Wien, Austria) is a new non-invasive surface cooling system. A comparison of these two induction methods has never been done before. Neither was the effect of EMCOOLS Flex.Pads on brain-temperature measured. For the first time iCOOL 2 compares feasibility, safety and efficacy of the two methods.

Official Title
-----------------
iCOOL 2 (Induction of COOLing 2): A Randomized Trial Comparing 2 Methods for Rapid Induction of Cooling in Stroke Patients, Cold Infusions vs. EMCOOLS Flex.Pads

Conditions
-----------------
Ischemic Stroke, Hemorrhagic Stroke

Intervention / Treatment
-----------------
* Drug: Cold crystalloid infusions, 0.9%NaCl or Ringer's solution
* Device: EMCOOLS Flex.Pads


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Sedation Combined ICP-temperature-probe Indication to lower body temperature > 1.5°C Age ≥ 18 years Exclusion Criteria: Body weight > 120 kg Severe renal insufficiency Acute pulmonary embolism Acute myocardial infarction High-grade heart valve stenosis or insufficiency Severe cardiac insufficiency (NYHA ≥ III) Threatening ventricular dysrhythmia Cardiac dysrhythmia with bradycardia (heart rate < 45 /min, QTc > 450 ms, sick sinus syndrome, AV-block II-III°). 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) Skin lesions not allowing a secure application of the EMCOOLS Flex.Pads

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cold infusions<br>Infusion of 2L cold crystalloid solution (4°C) over 30 minutes | Drug: Cold crystalloid infusions, 0.9%NaCl or Ringer's solution<br>* Infusion of 2L cold crystalloid solution (4°C) over 30 minutes<br>|
| Active Comparator: EMCOOLS Flex.Pads<br>Passive surface cooling with 10 EMCOOLS Flex.Pads (Emergency Medical Cooling Systems AG, Wien, Austria) | Device: EMCOOLS Flex.Pads<br>* Passive whole-body surface cooling with 10 EMCOOLS Flex.Pads<br>* Other names: Emergency Medical Cooling Systems AG, Wien, Austria;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain temperature | Primary endpoint: Change of brain temperature during one hour after start of cooling. Repeated measurement ANOVA for within subject contrasts (phase 1 (0 to 15min), 2 (15 to 30min), 3 (30 to 45min) and 4 (45 to 60min)) vs. baseline (-15 to 0min) | -15 to +60min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| (Neuro-)vital parameters | Effects on (neuro-)vital parameters (e.g. HR, AP, ICP, CPP) are registered | -15 to +180 min | 
| Cerebral autoregulation | Cerebral auto-regulation parameters (e.g. PRx) are calculated on the basis of the (neuro-)vital parameters monitored. | 15 to +180 min | 
| Safety | Various safety parameters, such as bleeding complications, cardiac decompensation, or local skin irritations are assessed. | 0 - 7 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
hypothermia, induction of hypothermia, cold infusion, whole-body cooling, external cooling, surface cooling, non invasive cooling, stroke, intracranial hemorrhage, cerebrovascular disease, neuro intensive care