Safety and Feasibility Study of Targeted Temperature Management After ICH

Morbidity and mortality from intra-cerebral/intra-parenchymal hemorrhage (ICH/IPH) are important public health problems. As the most common etiology of ICH/IPH is hypertension, this places a large proportion of the population at risk. In 2011 The American Heart Association (AHA) estimated that in the US, there were 610,000 new stroke cases of which 10% were ICHs, and many required long-term health care. ICH/IPH is associated with the highest morbidity and mortality and only 20% of patients regain functional independence. Temperature modulation to hypothermia (T, 32-34°C) has been associated with modulation of physiopathologic processes associated with inflammatory activation and degradation of blood-brain barrier after all types of brain injury. Currently, there are no therapies to specifically target ICH/IPH. To this end, novel strategies that go beyond control of glucose, blood pressure, and intra-cranial pressure, aimed at reducing the enlargement of the hematoma and "swelling" surrounding it, could be "the new frontier in the management of ICH/IPH". Since the early resuscitation phase in the Neuro-ICU represents the greatest opportunity for impact on clinical outcome after ICH/IPH, it also appears to be the most promising window of opportunity to demonstrate a benefit when investigating novel therapies.

• Normothermia (Other): 72 hours of targeted temperature management to achieve normothermia (36-37°C)
• Hypothermia (Other): 72 hours of targeted temperature management to achieve hypothermia (32-34°C)

Primary outcomes

• Severe adverse events (SAEs) [90 days]: The primary outcome measures will be: a) the frequency of adverse events (AEs) that will be possibly or probably related to treatment. AEs will be assessed up to 15-days after admission or discharge if earlier, and b) the frequency of severe adverse events (SAEs) that will be possibly and probably related to treatment.

Secondary outcomes

• In-hospital neurological deterioration between day 0-7 [7 days]: Decrease in GCS in ≥2 points or increase in the NIHSS ≥4 points
• Functional outcome [Discharge and 90 days]: Modified Rankin Scale at discharge and 90-days.
• Hematoma growth [24 hours]: Absolute change in hematoma between baseline and 24 hours CT-scan and new or absolute change in IVH between baseline and 24 hours CT-scan
• Cerebral edema [24, 48,72, and 168-hours]: The absolute change in cerebral edema and the relative change in cerebral edema (absolute edema/absolute ICH volume unit less ratio)

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Spontaneous supratentorial ICH documented by CT scan within 18 hours after the onset of symptoms
* Admission to the Neuro-ICU
* Baseline hematoma >15cc with or without IVH
* Need for mechanical ventilation.

Exclusion Criteria:

* GCS <6
* Age <18 years
* Pregnancy
* Pre-morbid modified Rankin Scale (mRS) >2
* Do Not Resuscitate (DNR) order "prior" to enrollment
* Uncontrolled bleeding of different etiology (trauma, gastro-intestinal bleeding \[UGIB/LGIB\])
* Planned surgical decompression within 24 hours
* Secondary causes of ICH (ischemic stroke, coagulopathy \[INR>1.4, aPTT> 1.5 times baseline, thrombocytopenia platelets <100,000/uL\], trauma, AVM, aneurysm, cerebral sinus thrombosis, or other causes)
* Evidence of sepsis
* Spontaneous hypothermia (core Temperature <36C)
* Inability to obtain written informed consent
* Participation in another trial.

• Fred Rincon, MD, MSc, Principal investigator, Thomas Jefferson University