<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01665885</url>
  </required_header>
  <id_info>
    <org_study_id>HAIS-SE</org_study_id>
    <nct_id>NCT01665885</nct_id>
  </id_info>
  <brief_title>Hypothermia in Acute Ischemic Stroke - Surface Versus Endovascular Cooling (HAIS-SE)</brief_title>
  <acronym>HAIS-SE</acronym>
  <official_title>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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital Heidelberg</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>ZOLL Circulation, Inc., USA</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital Heidelberg</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      HAIS-SE is evaluating for the first time ever in a randomized controlled trial efficacy,&#xD;
      tolerability, practicability and safety of endovascular versus surface cooling in awake&#xD;
      stroke patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Mild hypothermia improves outcome in patients with global cerebral ischemia after cardiac&#xD;
      arrest. Via animal models hypothermia has been identified as the most promising&#xD;
      neuroprotective therapy in focal cerebral ischemia as well. But the prove of clinical benefit&#xD;
      in patients with acute ischemic stroke is still missing: Most likely due to the prolonged&#xD;
      time window until hypothermia-induction (14 h) in previous studies. In addition, feasibility&#xD;
      of the method through which hypothermia is applied is crucial for a broad implementation of&#xD;
      hypothermia in stroke therapy. Surface versus endovascular cooling have never been compared&#xD;
      in a prospective trial in awake stroke patients.&#xD;
&#xD;
      HAIS-SE is evaluating for the first time ever in a randomized controlled trial efficacy,&#xD;
      tolerability, practicability and safety of endovascular versus surface cooling in awake&#xD;
      stroke patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>August 2012</start_date>
  <completion_date type="Anticipated">November 2015</completion_date>
  <primary_completion_date type="Anticipated">August 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Body core temperature</measure>
    <time_frame>0 to 48h</time_frame>
    <description>Primary endpoint: Time to primary target body core temperature (34°C) after hypothermia-induction.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Efficacy</measure>
    <time_frame>0 to 48h</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tolerability</measure>
    <time_frame>0 to 48h</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Practicability</measure>
    <time_frame>0 to 48h</time_frame>
    <description>Practicability outcome measures include a specific Hypothermia Nursing Staff Experience Questionnaire (HNEQ).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety</measure>
    <time_frame>0 to d90</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Ischemic Stroke</condition>
  <condition>Thrombolysis</condition>
  <condition>Hypothermia</condition>
  <arm_group>
    <arm_group_label>Endovascular cooling</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Endovascular cooling using the cooling device ZOLL Thermogard XP with ZOLL Quattro cooling catheter</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Surface cooling</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Surface cooling using the cooling device BARD/Medivance Arctic Sun 5000 with BARD/Medivance Arctic Gel Pads</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Best medical treatment following international stroke guidelines</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>ZOLL Thermogard XP</intervention_name>
    <description>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.</description>
    <arm_group_label>Endovascular cooling</arm_group_label>
    <other_name>ZOLL Thermogard XP cooling device, ZOLL Circulation, Inc., USA</other_name>
    <other_name>ZOLL Quattro cooling catheter, ZOLL Circulation, Inc., USA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>BARD/Medivance Arctic Sun 5000</intervention_name>
    <description>Induction of hypothermia with 1L cold crystalloid infusions (0,9%NaCl or Ringer's solution) and simultaneous start of surface cooling.</description>
    <arm_group_label>Surface cooling</arm_group_label>
    <other_name>BARD/Medivance Arctic Sun 5000, C. R. Bard, Inc., USA</other_name>
    <other_name>BARD/Medivance Arctic Gel Pads, C. R. Bard, Inc., USA</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ischemic stroke&#xD;
&#xD;
          -  Intravenous thrombolysis within 4.5h from symptom onset&#xD;
&#xD;
          -  Informed consent of the patient&#xD;
&#xD;
          -  NIHSS score ≥ 2 and ≤ 20&#xD;
&#xD;
          -  Age ≥ 18 and ≤ 90 years&#xD;
&#xD;
          -  Placement of cooling catheter / cooling pads within 6h from symptom onset&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  (Expected) intubation (e.g. for interventional treatment)&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Body weight &gt; 120kg&#xD;
&#xD;
          -  Body height &lt; 150cm&#xD;
&#xD;
          -  Life-expectancy &lt; 3 months&#xD;
&#xD;
          -  Fever &gt; 38.5°C at screening&#xD;
&#xD;
          -  Known hematologic disease with increased risk of thrombosis (e.g. cryoglobulinemia,&#xD;
             cold agglutinins, sickle cell anemia)&#xD;
&#xD;
          -  Known vasospastic vascular disorder (e.g. Raynaud's phenomenon or thromboangiitis&#xD;
             obliterans)&#xD;
&#xD;
          -  Possible compression of the inferior vena cava (e.g. due to tumor) or vena cava filter&#xD;
&#xD;
          -  Acute pulmonary embolism&#xD;
&#xD;
          -  Acute myocardial infarction&#xD;
&#xD;
          -  Severe cardiac insufficiency (NYHA ≥ III)&#xD;
&#xD;
          -  Threatening ventricular dysrhythmia&#xD;
&#xD;
          -  QTc-interval &gt; 450ms&#xD;
&#xD;
          -  Bradycardia &lt; 50/min&#xD;
&#xD;
          -  Sick-Sinus-Syndrom&#xD;
&#xD;
          -  AV-block &gt; I°&#xD;
&#xD;
          -  Severe infection with bacteremia or sepsis ≤ 72h&#xD;
&#xD;
          -  Severe renal (GFR &lt; 30ml/min) or liver insufficiency (Child-Pugh C)&#xD;
&#xD;
          -  Myopathy&#xD;
&#xD;
          -  Known intolerance or allergy against acetaminophen, buspirone, clonidine, magnesium&#xD;
             sulphate or pethidine.&#xD;
&#xD;
          -  Treatment with MAO-inhibitors ≤ 14 days&#xD;
&#xD;
          -  Acute closed-angle glaucoma&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sven Poli, Dr. med.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Heidelberg</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stroke Unit, Dept. of Neurology, University Hospital Heidelberg</name>
      <address>
        <city>Heidelberg</city>
        <zip>69120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>June 2013</verification_date>
  <study_first_submitted>August 13, 2012</study_first_submitted>
  <study_first_submitted_qc>August 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 15, 2012</study_first_posted>
  <last_update_submitted>February 16, 2015</last_update_submitted>
  <last_update_submitted_qc>February 16, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 18, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital Heidelberg</investigator_affiliation>
    <investigator_full_name>Dr. Sven Poli, MD MSc FESO</investigator_full_name>
    <investigator_title>Dr. Sven Poli, Consultant Neurologist, Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>hypothermia</keyword>
  <keyword>induction of hypothermia</keyword>
  <keyword>non invasive cooling</keyword>
  <keyword>external cooling</keyword>
  <keyword>surface cooling</keyword>
  <keyword>endovascular cooling</keyword>
  <keyword>cooling catheter</keyword>
  <keyword>stroke</keyword>
  <keyword>shivering</keyword>
  <keyword>neuro monitoring</keyword>
  <keyword>coagulation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
    <mesh_term>Ischemic Stroke</mesh_term>
    <mesh_term>Cerebral Infarction</mesh_term>
    <mesh_term>Ischemia</mesh_term>
    <mesh_term>Hypothermia</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01665885
org study id: HAIS-SE
nct id: NCT01665885
lead sponsor: 
collaborator: 
has dmc: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Body core temperature
time frame: 0 to 48h
description: Primary endpoint: Time to primary target body core temperature (34°C) after hypothermia-induction.
measure: Efficacy
time frame: 0 to 48h
description: 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.
measure: Tolerability
time frame: 0 to 48h
description: 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.
measure: Practicability
time frame: 0 to 48h
description: Practicability outcome measures include a specific Hypothermia Nursing Staff Experience Questionnaire (HNEQ).
measure: Safety
time frame: 0 to d90
description: 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.
arm group label: Endovascular cooling
arm group type: Active Comparator
description: Endovascular cooling using the cooling device ZOLL Thermogard XP with ZOLL Quattro cooling catheter
arm group label: Surface cooling
arm group type: Active Comparator
description: Surface cooling using the cooling device BARD/Medivance Arctic Sun 5000 with BARD/Medivance Arctic Gel Pads
arm group label: Control group
arm group type: No Intervention
description: Best medical treatment following international stroke guidelines
intervention type: Device
intervention name: ZOLL Thermogard XP
description: 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.
arm group label: Endovascular cooling
other name: ZOLL Thermogard XP cooling device, ZOLL Circulation, Inc., USA
other name: ZOLL Quattro cooling catheter, ZOLL Circulation, Inc., USA
intervention type: Device
intervention name: BARD/Medivance Arctic Sun 5000
description: Induction of hypothermia with 1L cold crystalloid infusions (0,9%NaCl or Ringer's solution) and simultaneous start of surface cooling.
arm group label: Surface cooling
other name: BARD/Medivance Arctic Sun 5000, C. R. Bard, Inc., USA
other name: BARD/Medivance Arctic Gel Pads, C. R. Bard, Inc., USA
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: Sven Poli, Dr. med.
role: Principal Investigator
affiliation: University Hospital Heidelberg
facility: 
country: Germany
responsible party type: Principal Investigator
investigator affiliation: University Hospital Heidelberg
investigator full name: Dr. Sven Poli, MD MSc FESO
investigator title: Dr. Sven Poli, Consultant Neurologist, Principal Investigator
mesh term: Stroke
mesh term: Ischemic Stroke
mesh term: Cerebral Infarction
mesh term: Ischemia
mesh term: Hypothermia