Subdural Hematoma, Traumatic
Conditions
Keywords
Subdural Hematoma, Traumatic Brain Injury, Hypothermia
Brief summary
This randomized, prospective trial will study the effect of very early cooling in patients undergoing surgical evacuation of acute subdural hematomas (35°C prior to opening the dura followed by maintenance at 33°C for a minimum of 48h). Intravascular cooling catheters (Thermogard XP Device, Zoll) will be utilized to induce hypothermia or to maintain normothermia. The primary objective is to determine if rapid induction of hypothermia prior to emergent craniotomy for traumatic subdural hematoma (SDH) will improve outcome as measured by Glasgow Outcome Scale-Extended (GOSE) at 6 months.
Interventions
DEVICETemperature management Zoll Intravascular Temperature Management device
Sponsors
The Vivian L. Smith Center for Neurologic Research
Zoll Medical Corporation
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
22 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Non-penetrating traumatic brain injury * Glasgow Coma Scale (GCS) motor score ≤5 (not following commands) * Estimated or known age 22-65 years * Acute subdural hematoma requiring emergent craniotomy within 6 hours of initial injury * Estimated time of injury to time to reach temp of 35°C\<6 hrs
Exclusion criteria
* Total GCS = 3 and bilateral fixed and dilated pupils * Following commands after an initial period of coma (GSC motor score of 6) * Known pre-existing neurological deficit (e.g., previous traumatic brain injury (TBI), stroke) * Concomitant spinal cord injury * Arrival temperature is \<35°C * Hemodynamic instability (i.e., mean arterial pressure (MAP)\<60 millimetres of mercury (mmHg) for 30 minutes) * Active cardiac dysrhythmia resulting in hemodynamic instability * Pregnancy * Duret hemorrhage * Prisoner or Ward of the State * Known history of clotting disorder (e.g., heparin induced thrombocytopenia, pulmonary embolism/deep venous thrombosis) * Injury to other body organ where hypothermia would be precluded because of bleeding risk (e.g., grade 3 liver laceration; bowel laceration; flail lung or international normalized ratio (INR) \>1.4) * Inability to obtain informed consent or utilize exception to informed consent for emergency research.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Favorable Glasgow Outcome Score-Extended (GOS-E) at 6 Months Post Injury | 6 months post injury | Participants were monitored for 6 months after injury, and GOS-E was scored as favorable (moderate disability to good recovery) or unfavorable (severe disability, vegetative state, or death) at 6 months post-injury. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intensive Care Unit (ICU) Length of Stay | from ICU admission to ICU discharge (median of about 11 to 13 days) | — |
| Hospital Length of Stay | from hospital admission to hospital discharge (median of about 18 to 21 days) | — |
| Incidence of Cortical Spreading Depolarization | 6 months | — |
| Safety as Assessed by Number of Adverse Events Reported Per Participant | 6 months post injury | Adverse events were graded according to the USDHHS Common Terminology Criteria for Adverse Events V4.0. Serious adverse events and pre-defined adverse events of interest that historically were known to be of concern with hypothermia treatment were selected to be monitored and reported regardless of grade. These included cardiac arrhythmias, thromboembolic events, pneumonia, bleeding or hemorrhage, intraoperative hemorrhage, infection (culture positive, e.g., blood stream infection, urinary tract infection, ventriculitis), device-related infection, and death. The number of adverse events per participant were compared between groups. |
Countries
Japan, United States
Participant flow
Recruitment details
Subjects were randomized and enrolled prior to evacuation of Subdural hematoma
Participants by arm
| Arm | Count |
|---|---|
| Normothermia Control, temperature maintained at 37 degrees C | 16 |
| Hypothermia treatment group, temperature at 35 degrees C at dura opening then 33 degrees C \> 48 hours | 16 |
| Total | 32 |
Baseline characteristics
| Characteristic | Normothermia | Hypothermia | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 2 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 14 Participants | 30 Participants |
| Age, Continuous | 41.2 years STANDARD_DEVIATION 12.7 | 46.6 years STANDARD_DEVIATION 15.1 | 43.9 years STANDARD_DEVIATION 14 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 11 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 4 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 10 Participants | 20 Participants |
| Region of Enrollment Japan | 4 participants | 3 participants | 7 participants |
| Region of Enrollment United States | 12 participants | 13 participants | 25 participants |
| Sex: Female, Male Participants Female | 2 Participants | 5 Participants | 7 Participants |
| Sex: Female, Male Participants Male | 14 Participants | 11 Participants | 25 Participants |
| Subdural hematoma present | 16 Participants | 16 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 16 | 3 / 16 |
| other Total, other adverse events | 10 / 16 | 12 / 16 |
| serious Total, serious adverse events | 10 / 16 | 11 / 16 |
Outcome results
Primary
Number of Participants With Favorable Glasgow Outcome Score-Extended (GOS-E) at 6 Months Post Injury
Participants were monitored for 6 months after injury, and GOS-E was scored as favorable (moderate disability to good recovery) or unfavorable (severe disability, vegetative state, or death) at 6 months post-injury.
Time frame: 6 months post injury
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Normothermia | Number of Participants With Favorable Glasgow Outcome Score-Extended (GOS-E) at 6 Months Post Injury | 4 Participants |
| Hypothermia | Number of Participants With Favorable Glasgow Outcome Score-Extended (GOS-E) at 6 Months Post Injury | 6 Participants |
Secondary
Hospital Length of Stay
Time frame: from hospital admission to hospital discharge (median of about 18 to 21 days)
Population: Data was not collected for one participant in the normothermia arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Normothermia | Hospital Length of Stay | 18.243 days |
| Hypothermia | Hospital Length of Stay | 20.674 days |
Secondary
Incidence of Cortical Spreading Depolarization
Time frame: 6 months
Population: Data was not collected for this outcome measure.
Secondary
Intensive Care Unit (ICU) Length of Stay
Time frame: from ICU admission to ICU discharge (median of about 11 to 13 days)
Population: Data was not collected for one participant in the normothermia arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Normothermia | Intensive Care Unit (ICU) Length of Stay | 11.390 days |
| Hypothermia | Intensive Care Unit (ICU) Length of Stay | 12.946 days |
Secondary
Safety as Assessed by Number of Adverse Events Reported Per Participant
Adverse events were graded according to the USDHHS Common Terminology Criteria for Adverse Events V4.0. Serious adverse events and pre-defined adverse events of interest that historically were known to be of concern with hypothermia treatment were selected to be monitored and reported regardless of grade. These included cardiac arrhythmias, thromboembolic events, pneumonia, bleeding or hemorrhage, intraoperative hemorrhage, infection (culture positive, e.g., blood stream infection, urinary tract infection, ventriculitis), device-related infection, and death. The number of adverse events per participant were compared between groups.
Time frame: 6 months post injury
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Normothermia | Safety as Assessed by Number of Adverse Events Reported Per Participant | 4.500 number of adverse events per participant |
| Hypothermia | Safety as Assessed by Number of Adverse Events Reported Per Participant | 4.000 number of adverse events per participant |