Clinical trial NCT01866384: Targeted Temperature Management After Intracerebral Hemorrhage
Official title: Safety and Tolerability of a Protocol of Targeted Temperature Management After Intracerebral Hemorrhage
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Cerebral Hemorrhage
Hypothermia
Lead sponsor: Thomas Jefferson University
Sponsor class: OTHER
First posted: 2013-05-31
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: Early hematoma growth (HG) after spontaneous intra-cerebral/intra-parenchymal hemorrhage (IPH) is common and associated with neurological deterioration and poor clinical outcome. Temperature modulation to hypothermia (Temperature, 32-34°C) has been associated with reduction or improvement of physiopathologic processes associated with inflammatory activation and degradation of blood-brain barrier after all types of brain injury. In this sense, we believe that the initiation of an ultra-early protocol of active temperature modulation or Targeted Temperature Management (TTM) to mild induced hypothermia (MIH, 32-34°C) may be associated with good safety and tolerability profile, less HG and cerebral edema after IPH by modulation of systemic and local inflammatory responses, so we hypothesize that TTM to MIH will be a safe/tolerable and effective therapy to limit HG and cerebral edema after IPH.

Detailed description: In this randomized clinical trial, patients with IPH within 6 hours of onset will be randomized to one of two study arms. In one arm, patients will have 72 hours of TTM to MIH (32-34 degree Celcius). In the second arm, patients will have 72 hours of TTM to Normal Temperature (NT)(36-37 degrees Celcius). Subjects in all arms will otherwise receive identical therapeutic interventions pre-defined by our local IPH management protocol.

Primary outcomes are examining 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 the frequency of severe adverse events (SAEs) that will be possibly and probably related to treatment.

SAEs will be assessed up to 90-days.

The secondary outcome measures will be in-hospital neurological deterioration between day 0-7 (decrease in GCS10 in ≥2 points, or increase in the NIHSS11 ≥4 points), in-hospital mortality, modified Rankin Score \[mRS\]12 at discharge and 90-days.

To determine whether TTM to MIH can limit HG and cerebral edema, will be examining absolute change in hematoma between baseline and 24 hours, new or absolute change in IVH between baseline and 24 hours, the proportion of patients with HG, absolute change in hemostatic proteins, the absolute change in cerebral edema between baseline and 24, 48,72, and 168-hours, relative change in cerebral edema.

Eligibility criteria: Inclusion Criteria:

* spontaneous supratentorial IPH documented by CT scan within 6 hours after the onset of symptoms and 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 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 IPH (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
* inability to obtain written informed consent
* participation in another trial

Primary outcomes:
measure: Frequency of adverse events (AEs) that will be possibly or probably related to the treatment.
timeFrame: Continuous throughout 3 year study period
Secondary outcomes:
measure: In-hospital neurological deterioration between day 0-7.
timeFrame: Continuous throughout 3 year study period
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
Study officials:
affiliation: Thomas Jefferson University
name: Fred Rincon, MD
role: PRINCIPAL_INVESTIGATOR
References: