Safety and Feasibility Study of Targeted Temperature Management After ICH

Study Overview
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Brief Summary
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Though TTM is ubiquitously used in the neuro-intensive care unit, there is limited experience with the use of TTM after intracerebral hemorrhage (ICH), the most devastating type of stroke. TTM may be a an intervention to improve patient outcomes. This trial addresses the safety and tolerability of a protocol of ultra-early TTM after ICH/IPH and may be the basis for future larger clinical trials.

Detailed Description
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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.

Official Title
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Safety and Feasibility of a Protocol of Targeted Temperature Management After Intracerebral Hemorrhage

Conditions
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Intracerebral Hemorrhage

Intervention / Treatment
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* Other: Normothermia
* Other: Hypothermia


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Normothermia<br>Core temperature 36-37 C | Other: Normothermia<br>* 72 hours of targeted temperature management to achieve normothermia (36-37°C)<br>|
| Experimental: Hypothermia<br>Core temperature 32-34 C | Other: Hypothermia<br>* 72 hours of targeted temperature management to achieve hypothermia (32-34°C)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severe adverse events (SAEs) | 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. | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In-hospital neurological deterioration between day 0-7 | Decrease in GCS in ≥2 points or increase in the NIHSS ≥4 points | 7 days | 
| Functional outcome | Modified Rankin Scale at discharge and 90-days. | Discharge and 90 days | 
| Hematoma growth | 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 | 24 hours | 
| Cerebral edema | The absolute change in cerebral edema and the relative change in cerebral edema (absolute edema/absolute ICH volume unit less ratio) | 24, 48,72, and 168-hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypothermia, normothermia, hyperthermia