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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cerebral Hemorrhage; Hypothermia	Procedure: mild induced hypothermia; Other: Normal Temperature	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Primary Purpose: Treatment
• Official Title: Safety and Tolerability of a Protocol of Targeted Temperature Management After Intracerebral Hemorrhage
• Study Start Date: September 2012
• Estimated Primary Completion Date: September 2015

Arms and Interventions

Arm	Intervention/treatment
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.	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).
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.	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).

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Jennifer Glendening, MSN, RN; 215-955-7962; jennifer.glendening@jefferson.edu

Contact: John Furlong, RN,CCRC; 215-955-7301; john.furlong@jefferson.edu

Locations

United States, Pennsylvania

Thomas Jefferson University Hospital; Recruiting

Philadelphia, Pennsylvania, United States, 19107

Contact: Meghan Wakefield, RN,CCRP 215-503-9110 meghan.wakefield@jefferson.edu

Principal Investigator: Fred Rincon, MD

Sponsors and Collaborators

Thomas Jefferson University

Investigators

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

More Information

• Responsible Party: Thomas Jefferson University
• ClinicalTrials.gov Identifier: NCT01866384
• Other Study ID Numbers: 12D.466
• First Posted: May 31, 2013
• Last Update Posted: December 18, 2014
• Last Verified: December 2014

Additional relevant MeSH terms:

Body Temperature Changes; Cerebral Hemorrhage; Hemorrhage; Hypothermia; Pathologic Processes; Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases