Reperfusion With Cooling in Cerebral Acute Ischemia II (ReCCLAIM II)

This study has been withdrawn prior to enrollment.
(unable to be funded)
Sponsor:
Information provided by (Responsible Party):
Christopher M. Horn, MD, Emory University
ClinicalTrials.gov Identifier:
NCT01728649
First received: September 5, 2012
Last updated: November 10, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Ischemic Stroke
Hypothermia
Other: Mild Hypothermia
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Study of Mild Hypothermia in Combination With Acute Cerebral Vascular Reperfusion in the Setting of Acute Ischemic Stroke

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Number of participants with adverse events [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
    Evaluation and determination of the following complications pneumonias, central line infections, intra-cerebral hemorrhages, systemic hemorrhages, transient cerebral ischemia, and new strokes.


Secondary Outcome Measures:
  • Hyperintense Acute Reperfusion Marker (HARM) [ Time Frame: 48+/- 24 hours ] [ Designated as safety issue: No ]
    HARM is a MRI sequence looking at gadolinium enhancement on FLAIR MRI imaging.

  • Hemorrhagic Conversion [ Time Frame: 48hrs ] [ Designated as safety issue: Yes ]
    Acute bleeding into the area of the original stroke based on CT or MRI of the head.

  • National Institutes of Health Stroke Scale (NIHSS) [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    NIHSS is a scale from 1-42 to evaluate stroke severity

  • Modified Rankin Scale (mRS) [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    mRS is a straightforward evaluation of the functional limitations from stroke

  • Biomarkers [ Time Frame: Before therapy then immediately after, 8hrs, and 24hrs after reperfusion ] [ Designated as safety issue: No ]
    These biomarkers are indicative of ischemia-reperfusion injury


Enrollment: 0
Study Start Date: February 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Normothermia
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.
Experimental: Mild Hypothermia
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.
Other: Mild Hypothermia
Hypothermia will be achieved using the Zoll Thermogaurd XP technology with the Quattro catheter. This catheter has a 9.3 Fr diameter and is 43cm 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.
Other Names:
  • Hypothermia
  • Theraputic Hypothermia

Detailed Description:

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.
  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female subjects of any ethnicity and age >/=18 but </= 85 years;
  • Symptom onset </=8 hours;
  • Symptoms consistent with an ischemic stroke with a large vessel occlusion (Middle Cerebral Artery (MCA), Internal Carotid Artery (ICA) terminus) as determined by vascular imaging, CT or MRI;
  • Alberta Stroke Program Early CT Score (ASPECTS) of 5-10 on non-contrast CT of the brain;
  • Ability to undergo endovascular reperfusion therapy;
  • No contraindications to general anesthesia or allergies to any components associated with the anticipated diagnostic or treatment procedures that cannot be treated;
  • A pre-treatment modified Rankin Scale (mRS) of 0 or 1;
  • Arterial puncture performed under 8 hours from symptom onset or last seen normal
  • Baseline MRI or CT scan shows no hemorrhage;
  • National Institutes of Health Stroke Scale (NIHSS) 14-29;
  • Subject has either 1) failed iv tissue plasminogen activator (tPA) therapy or 2) contradicted for iv tPA therapy;
  • Subject is capable of complying with study procedures and agrees to complete all required study procedures, study visits and associated activities.
  • Subject must be able to understand and give written informed consent.

Exclusion Criteria:

  • Females of childbearing potential who are pregnant or not using adequate contraception;
  • Bleeding diathesis with a platelet count < 50,000 or International Normalized Ratio (INR) >1.5 or any active or recent (within 10 to 30 days) hemorrhage;
  • History of genetically confirmed hypercoagulable syndrome;
  • Any condition that excludes MRI imaging;
  • History of dementia, currently on Aricept or Namenda, or other Alzheimer's like symptoms;
  • End stage renal disease on hemodialysis;
  • History of cardiac arrest;
  • Presence of an inferior vena cava (IVC) filter;
  • Contrast dye allergy with history of anaphylaxis, known serious sensitivity to contrast agents or any condition in which angiography is contraindicated;
  • Known allergy to meperidine or buspar;
  • Sustained hypertension (systolic blood pressure (SBP) > 185 or diastolic blood pressure (DBP) > 110 refractory to treatment);
  • Baseline CT/MRI of head showing evidence of mass effect with mid-line shift, hemorrhage, intracranial tumor, arterial vasculitis or dissection, or bilateral stroke;
  • Presence of any other serious comorbidity that would be likely to impact life expectancy to less than 6 months or limit subject cooperation or study compliance;
  • Concurrent participation in an investigational clinical study that has not completed the follow-up period or planned participation in another study within the next 3 months;
  • Subject has any other condition or personal circumstance that, in the judgment of the investigator, might interfere with the collection of complete, good quality data or the completion of the research study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01728649

Locations
United States, Georgia
Grady Memorial Hospital
Atlanta, Georgia, United States, 30303
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Christopher Horn, MD Emory University
Study Director: Rishi Gupta, MD Emory University
  More Information

No publications provided

Responsible Party: Christopher M. Horn, MD, Assistant Professor of Neurology and Neurosurgery, Emory University
ClinicalTrials.gov Identifier: NCT01728649     History of Changes
Other Study ID Numbers: MSNC 02
Study First Received: September 5, 2012
Last Updated: November 10, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Emory University:
Acute Ischemic Stroke
Mild Hypothermia
Stroke
Hypothermia

Additional relevant MeSH terms:
Hypothermia
Ischemia
Stroke
Cerebral Infarction
Body Temperature Changes
Signs and Symptoms
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia

ClinicalTrials.gov processed this record on July 10, 2014