Safety and Feasibility Study of Targeted Temperature Management After ICH (TTM-ICH)

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

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.

Study Overview

• Status: Unknown
• Conditions: Intracerebral Hemorrhage
• Intervention / Treatment: Other: Normothermia; Other: Hypothermia

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 Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital

Participation Criteria

Eligibility Criteria

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

Description

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.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Normothermia; Core temperature 36-37 C	Other: Normothermia; 72 hours of targeted temperature management to achieve normothermia (36-37°C)
Experimental: Hypothermia; Core temperature 32-34 C	Other: Hypothermia; 72 hours of targeted temperature management to achieve hypothermia (32-34°C)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severe adverse events (SAEs)	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.	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In-hospital neurological deterioration between day 0-7	Decrease in GCS in ≥2 points or increase in the NIHSS ≥4 points	7 days
Functional outcome	Modified Rankin Scale at discharge and 90-days.	Discharge and 90 days
Hematoma growth	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	24 hours
Cerebral edema	The absolute change in cerebral edema and the relative change in cerebral edema (absolute edema/absolute ICH volume unit less ratio)	24, 48,72, and 168-hours

Collaborators and Investigators

• Sponsor: Thomas Jefferson University
• Collaborators: American Heart Association
• Investigators: Principal Investigator: Fred Rincon, MD, MSc, Thomas Jefferson University

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): June 1, 2015
• Study Completion (Anticipated): June 1, 2016

Study Registration Dates

• First Submitted: May 24, 2012
• First Submitted That Met QC Criteria: May 25, 2012
• First Posted (Estimate): May 28, 2012

Study Record Updates

• Last Update Posted (Estimate): August 5, 2015
• Last Update Submitted That Met QC Criteria: August 4, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: hyperthermia; hypothermia; normothermia
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Cerebral Hemorrhage
• Other Study ID Numbers: 12CRP12050342