Safety and Feasibility Study of Targeted Temperature Management After ICH

Phase 1

• Conditions: Intracerebral Hemorrhage
• Interventions: Other: Normothermia; Other: Hypothermia

• Registration Number: NCT01607151
• Lead Sponsor: Thomas Jefferson University

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2012-05-24
• Study First Submitted QC: 2012-05-25
• Study First Posted: 2012-05-28
• Study Start: 2013-01
• Primary Completion: 2015-06
• Status Verified: 2015-08
• Last Update Submitted: 2015-08-04
• Last Update Posted: 2015-08-05
• Study Completion: 2016-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Normothermia	Normothermia	Core temperature 36-37 C
Hypothermia	Hypothermia	Core temperature 32-34 C

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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)

Trial Locations

Locations (1)

Thomas Jefferson University Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States