Targeted Temperature Management After Intracerebral Hemorrhage

Hypothermia Clinical Trial

Official title:

Safety and Tolerability of a Protocol of Targeted Temperature Management After Intracerebral Hemorrhage

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01866384
• Other study ID #: 12D.466
• Status: Recruiting
• Phase: Phase 2
• First received: May 20, 2013
• Last updated: December 16, 2014
• Start date: September 2012

Study information

• Verified date: December 2014
• Source: Thomas Jefferson University
• Contact: Jennifer Glendening, MSN, RN
• Phone: 215-955-7962
• Email: jennifer.glendening[@]jefferson.edu
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cerebral Hemorrhage
• Hemorrhage
• Hypothermia

Intervention

Procedure:
• mild induced hypothermia
Patients with intraparancymal hemorrhage within 6 hours of onset will be randomized to either the mild induced hypothermia group or the normal temperature group (control). In this arm, the patient will have 72 hours of Targeted Temperature Managment to mild induced hypothermia (32-34 degrees Celcius).

Other:
• Normal Temperature
In this arm, the patient will have standard of care intraparenchymal hemorrhage management per institutional policy, with normal body temperature management (36-37 degrees Celcius).

Locations

Country	Name	City	State
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Thomas Jefferson University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of adverse events (AEs) that will be possibly or probably related to the treatment.	To determine whether TTM to MIH is safe and tolerable after IPH measured by the frequency of adverse events (AEs) that will be possibly or probably related to the treatment.	Continuous throughout 3 year study period	Yes
Secondary	In-hospital neurological deterioration between day 0-7.	To determine whether TTM to MIH can limit hematoma growth and cerebral edema measured by in-hospital neurological deterioration between day 0-7.	Continuous throughout 3 year study period	Yes