Targeted Temperature Management After Intracerebral Hemorrhage

• ClinicalTrials.gov Identifier: NCT01866384
• Recruitment Status: Unknown
• First Posted: May 31, 2013
• Last Update Posted: December 18, 2014
• Sponsor: Thomas Jefferson University
• Information provided by (Responsible Party): Thomas Jefferson University

Tracking Information

• First Submitted Date: May 20, 2013
• First Posted Date: May 31, 2013
• Last Update Posted Date: December 18, 2014
• Study Start Date: September 2012
• Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 30, 2013)

Frequency of adverse events (AEs) that will be possibly or probably related to the treatment. [ Time Frame: Continuous throughout 3 year study period ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 30, 2013)

In-hospital neurological deterioration between day 0-7. [ Time Frame: Continuous throughout 3 year study period ]

To determine whether TTM to MIH can limit hematoma growth and cerebral edema measured by in-hospital neurological deterioration between day 0-7.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Targeted Temperature Management After Intracerebral Hemorrhage
• Official Title: Safety and Tolerability of a Protocol of Targeted Temperature Management After Intracerebral Hemorrhage
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Primary Purpose: Treatment

Condition

• Cerebral 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).

Study Arms

• Normal Temperature
  72 hours of Normal Temperature (36-37 degrees Celcius). Subjects in all arms will otherwise receive identical therapeutic interventions pre-defined by our local IPH management protocol.
  Intervention: Other: Normal Temperature
• Experimental: Mild Induced Hypothermia
  72 hours of mild induced hypothermia (32-34 degrees Celcius). Subjects in all arms will otherwise receive identical therapeutic interventions pre-defined by our local IPH management protocol.
  Intervention: Procedure: mild induced hypothermia

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: May 30, 2013): 100
• Original Estimated Enrollment: Same as current
• Study Completion Date: Not Provided
• Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01866384
• Other Study ID Numbers: 12D.466
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Thomas Jefferson University
• Study Sponsor: Thomas Jefferson University
• Collaborators: Not Provided

Investigators

• Principal Investigator: Fred Rincon, MD; Thomas Jefferson University

• PRS Account: Thomas Jefferson University
• Verification Date: December 2014