Reperfusion With Cooling in Cerebral Acute Ischemia II (ReCCLAIM II)
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.
|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|
- 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.
- 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
|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)|
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01728649
|United States, Georgia|
|Grady Memorial Hospital|
|Atlanta, Georgia, United States, 30303|
|Principal Investigator:||Christopher Horn, MD||Emory University|
|Study Director:||Rishi Gupta, MD||Emory University|