<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/NCT01728649</url>
  </required_header>
  <id_info>
    <org_study_id>MSNC 02</org_study_id>
    <nct_id>NCT01728649</nct_id>
  </id_info>
  <brief_title>Reperfusion With Cooling in Cerebral Acute Ischemia II</brief_title>
  <acronym>ReCCLAIM II</acronym>
  <official_title>Phase 2 Study of Mild Hypothermia in Combination With Acute Cerebral Vascular Reperfusion in the Setting of Acute Ischemic Stroke</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>WellStar Health System</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>WellStar Health System</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether reducing a patients body temperature (mild&#xD;
      hypothermia of 33 degrees Centigrade) will significantly reduce the risk of brain injury&#xD;
      (notably reperfusion injury and hemorrhagic conversion) in patients that have suffered a&#xD;
      significant interruption of blood flow to an area of brain (occlusion of large proximal&#xD;
      cerebral artery) and have undergone successful removal of that interruption&#xD;
      (revascularization).This will be achieved by comparing patients that have undergone&#xD;
      hypothermia to those that have not.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is designed to examine the safety and proof of concept of therapeutic hypothermia&#xD;
      prior to conventional revascularization in subjects experiencing acute ischemic stroke by&#xD;
      comparing the results to subjects who remain at normal body temperature (normothermic) and&#xD;
      proceed directly to reperfusion via conventional reperfusion intervention. The&#xD;
      investigational plan also examines the following outcomes in 85 subjects randomized to either&#xD;
      hypothermia or normothermia:&#xD;
&#xD;
        -  Regulation of biomarkers indicative of ischemia-reperfusion injury&#xD;
&#xD;
        -  Changes in blood brain injury using the Hyperintense Acute Reperfusion Marker (HARM)&#xD;
           protocol MRI as a surrogate imaging biomarker&#xD;
&#xD;
        -  Incidence of hemorrhagic conversion post reperfusion&#xD;
&#xD;
        -  Neurologic function at 90 days post acute ischemic stroke. The results of this study&#xD;
           will be used to power a definitive phase III clinical trial evaluating the combination&#xD;
           of hypothermia and revascularization versus reperfusion alone.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    unable to be funded&#xD;
  </why_stopped>
  <start_date>February 2013</start_date>
  <completion_date type="Anticipated">June 2015</completion_date>
  <primary_completion_date type="Anticipated">February 2015</primary_completion_date>
  <phase>N/A</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with adverse events</measure>
    <time_frame>90 days</time_frame>
    <description>Evaluation and determination of the following complications pneumonias, central line infections, intra-cerebral hemorrhages, systemic hemorrhages, transient cerebral ischemia, and new strokes.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hyperintense Acute Reperfusion Marker (HARM)</measure>
    <time_frame>48+/- 24 hours</time_frame>
    <description>HARM is a MRI sequence looking at gadolinium enhancement on FLAIR MRI imaging.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hemorrhagic Conversion</measure>
    <time_frame>48hrs</time_frame>
    <description>Acute bleeding into the area of the original stroke based on CT or MRI of the head.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>National Institutes of Health Stroke Scale (NIHSS)</measure>
    <time_frame>90 days</time_frame>
    <description>NIHSS is a scale from 1-42 to evaluate stroke severity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modified Rankin Scale (mRS)</measure>
    <time_frame>90 days</time_frame>
    <description>mRS is a straightforward evaluation of the functional limitations from stroke</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarkers</measure>
    <time_frame>Before therapy then immediately after, 8hrs, and 24hrs after reperfusion</time_frame>
    <description>These biomarkers are indicative of ischemia-reperfusion injury</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Ischemic Stroke</condition>
  <condition>Hypothermia</condition>
  <arm_group>
    <arm_group_label>Normothermia</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>As part of standard of care, an interventional reperfusion procedure will be performed on all subjects using current FDA approved devices. After which patient will be started on normothermia attempting to keep core body temp between 38 and 36.5 degrees centigrade. Patients will also undergo blood draws for biomarkers before reperfusion is achieved the immediately, 6 hours then 24 hours after reperfusion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mild Hypothermia</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>As part of standard of care, an interventional reperfusion procedure will be performed on all subjects using current FDA cleared device. Patient will also have a Quattro catheter placed in the femoral vein and temperature brought to 33 degrees centigrade as quickly as possible. They will stay in mild hypothermia for 12 hours and then be rewarmed very slowly. Patients will also undergo blood draws for biomarkers before reperfusion is achieved the immediately, 6 hours then 24 hours after reperfusion.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Mild Hypothermia</intervention_name>
    <description>Hypothermia will be achieved using the Zoll Thermoguard XP technology with the Quattro catheter. This catheter has a 9.3 Fr diameter and is 4 3cm long. It will be placed in the patients femoral vein via Seldinger technique, before reperfusion is achieved. Hypothermia will be initiated prior to reperfusion. Once temperature has reached 33.5 degrees centigrade the patient will remain at that temperature for 12 hours after which the patient will undergo active gradual rewarming at 0.2 degrees centigrade per hour.</description>
    <arm_group_label>Mild Hypothermia</arm_group_label>
    <other_name>Hypothermia</other_name>
    <other_name>Therapeutic Hypothermia</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female subjects of any ethnicity and age &gt;/=18 but &lt;/= 85 years;&#xD;
&#xD;
          -  Symptom onset &lt;/=8 hours;&#xD;
&#xD;
          -  Symptoms consistent with an ischemic stroke with a large vessel occlusion (Middle&#xD;
             Cerebral Artery (MCA), Internal Carotid Artery (ICA) terminus) as determined by&#xD;
             vascular imaging, CT or MRI;&#xD;
&#xD;
          -  Alberta Stroke Program Early CT Score (ASPECTS) of 5-10 on non-contrast CT of the&#xD;
             brain;&#xD;
&#xD;
          -  Ability to undergo endovascular reperfusion therapy;&#xD;
&#xD;
          -  No contraindications to general anesthesia or allergies to any components associated&#xD;
             with the anticipated diagnostic or treatment procedures that cannot be treated;&#xD;
&#xD;
          -  A pre-treatment modified Rankin Scale (mRS) of 0 or 1;&#xD;
&#xD;
          -  Arterial puncture performed under 8 hours from symptom onset or last seen normal&#xD;
&#xD;
          -  Baseline MRI or CT scan shows no hemorrhage;&#xD;
&#xD;
          -  National Institutes of Health Stroke Scale (NIHSS) 14-29;&#xD;
&#xD;
          -  Subject has either 1) failed iv tissue plasminogen activator (tPA) therapy or 2)&#xD;
             contradicted for iv tPA therapy;&#xD;
&#xD;
          -  Subject is capable of complying with study procedures and agrees to complete all&#xD;
             required study procedures, study visits and associated activities.&#xD;
&#xD;
          -  Subject must be able to understand and give written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Females of childbearing potential who are pregnant or not using adequate&#xD;
             contraception;&#xD;
&#xD;
          -  Bleeding diathesis with a platelet count &lt; 50,000 or International Normalized Ratio&#xD;
             (INR) &gt;1.5 or any active or recent (within 10 to 30 days) hemorrhage;&#xD;
&#xD;
          -  History of genetically confirmed hypercoagulable syndrome;&#xD;
&#xD;
          -  Any condition that excludes MRI imaging;&#xD;
&#xD;
          -  History of dementia, currently on Aricept or Namenda, or other Alzheimer's like&#xD;
             symptoms;&#xD;
&#xD;
          -  End stage renal disease on hemodialysis;&#xD;
&#xD;
          -  History of cardiac arrest;&#xD;
&#xD;
          -  Presence of an inferior vena cava (IVC) filter;&#xD;
&#xD;
          -  Contrast dye allergy with history of anaphylaxis, known serious sensitivity to&#xD;
             contrast agents or any condition in which angiography is contraindicated;&#xD;
&#xD;
          -  Known allergy to meperidine or buspar;&#xD;
&#xD;
          -  Sustained hypertension (systolic blood pressure (SBP) &gt; 185 or diastolic blood&#xD;
             pressure (DBP) &gt; 110 refractory to treatment);&#xD;
&#xD;
          -  Baseline CT/MRI of head showing evidence of mass effect with mid-line shift,&#xD;
             hemorrhage, intracranial tumor, arterial vasculitis or dissection, or bilateral&#xD;
             stroke;&#xD;
&#xD;
          -  Presence of any other serious comorbidity that would be likely to impact life&#xD;
             expectancy to less than 6 months or limit subject cooperation or study compliance;&#xD;
&#xD;
          -  Concurrent participation in an investigational clinical study that has not completed&#xD;
             the follow-up period or planned participation in another study within the next 3&#xD;
             months;&#xD;
&#xD;
          -  Subject has any other condition or personal circumstance that, in the judgment of the&#xD;
             investigator, might interfere with the collection of complete, good quality data or&#xD;
             the completion of the research study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christopher Horn, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rishi Gupta, MD</last_name>
    <role>Study Director</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Grady Memorial Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2018</verification_date>
  <study_first_submitted>September 5, 2012</study_first_submitted>
  <study_first_submitted_qc>November 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 20, 2012</study_first_posted>
  <last_update_submitted>September 11, 2018</last_update_submitted>
  <last_update_submitted_qc>September 11, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>WellStar Health System</investigator_affiliation>
    <investigator_full_name>Dr. Christopher Horn</investigator_full_name>
    <investigator_title>Assistant Professor of Neurology and Neurosurgery</investigator_title>
  </responsible_party>
  <keyword>Acute Ischemic Stroke</keyword>
  <keyword>Mild Hypothermia</keyword>
  <keyword>Stroke</keyword>
  <keyword>Hypothermia</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>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/NCT01728649
org study id: MSNC 02
nct id: NCT01728649
lead sponsor: 
has dmc: Yes
The purpose of this study is to determine whether reducing a patients body temperature (mild
      hypothermia of 33 degrees Centigrade) will significantly reduce the risk of brain injury
      (notably reperfusion injury and hemorrhagic conversion) in patients that have suffered a
      significant interruption of blood flow to an area of brain (occlusion of large proximal
      cerebral artery) and have undergone successful removal of that interruption
      (revascularization).This will be achieved by comparing patients that have undergone
      hypothermia to those that have not.
This study is designed to examine the safety and proof of concept of therapeutic hypothermia
      prior to conventional revascularization in subjects experiencing acute ischemic stroke by
      comparing the results to subjects who remain at normal body temperature (normothermic) and
      proceed directly to reperfusion via conventional reperfusion intervention. The
      investigational plan also examines the following outcomes in 85 subjects randomized to either
      hypothermia or normothermia:

        -  Regulation of biomarkers indicative of ischemia-reperfusion injury

        -  Changes in blood brain injury using the Hyperintense Acute Reperfusion Marker (HARM)
           protocol MRI as a surrogate imaging biomarker

        -  Incidence of hemorrhagic conversion post reperfusion

        -  Neurologic function at 90 days post acute ischemic stroke. The results of this study
           will be used to power a definitive phase III clinical trial evaluating the combination
           of hypothermia and revascularization versus reperfusion alone.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with adverse events
time frame: 90 days
description: Evaluation and determination of the following complications pneumonias, central line infections, intra-cerebral hemorrhages, systemic hemorrhages, transient cerebral ischemia, and new strokes.
measure: Hyperintense Acute Reperfusion Marker (HARM)
time frame: 48+/- 24 hours
description: HARM is a MRI sequence looking at gadolinium enhancement on FLAIR MRI imaging.
measure: Hemorrhagic Conversion
time frame: 48hrs
description: Acute bleeding into the area of the original stroke based on CT or MRI of the head.
measure: National Institutes of Health Stroke Scale (NIHSS)
time frame: 90 days
description: NIHSS is a scale from 1-42 to evaluate stroke severity
measure: Modified Rankin Scale (mRS)
time frame: 90 days
description: mRS is a straightforward evaluation of the functional limitations from stroke
measure: Biomarkers
time frame: Before therapy then immediately after, 8hrs, and 24hrs after reperfusion
description: These biomarkers are indicative of ischemia-reperfusion injury
arm group label: Normothermia
arm group type: No Intervention
description: As part of standard of care, an interventional reperfusion procedure will be performed on all subjects using current FDA approved devices. After which patient will be started on normothermia attempting to keep core body temp between 38 and 36.5 degrees centigrade. Patients will also undergo blood draws for biomarkers before reperfusion is achieved the immediately, 6 hours then 24 hours after reperfusion.
arm group label: Mild Hypothermia
arm group type: Experimental
description: As part of standard of care, an interventional reperfusion procedure will be performed on all subjects using current FDA cleared device. Patient will also have a Quattro catheter placed in the femoral vein and temperature brought to 33 degrees centigrade as quickly as possible. They will stay in mild hypothermia for 12 hours and then be rewarmed very slowly. Patients will also undergo blood draws for biomarkers before reperfusion is achieved the immediately, 6 hours then 24 hours after reperfusion.
intervention type: Other
intervention name: Mild Hypothermia
description: Hypothermia will be achieved using the Zoll Thermoguard XP technology with the Quattro catheter. This catheter has a 9.3 Fr diameter and is 4 3cm long. It will be placed in the patients femoral vein via Seldinger technique, before reperfusion is achieved. Hypothermia will be initiated prior to reperfusion. Once temperature has reached 33.5 degrees centigrade the patient will remain at that temperature for 12 hours after which the patient will undergo active gradual rewarming at 0.2 degrees centigrade per hour.
arm group label: Mild Hypothermia
other name: Hypothermia
other name: Therapeutic Hypothermia
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Christopher Horn, MD
role: Principal Investigator
affiliation: Emory University
last name: Rishi Gupta, MD
role: Study Director
affiliation: Emory University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: WellStar Health System
investigator full name: Dr. Christopher Horn
investigator title: Assistant Professor of Neurology and Neurosurgery
mesh term: Stroke
mesh term: Ischemic Stroke
mesh term: Ischemia
mesh term: Hypothermia