Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02351518 |
| Other study ID # |
HP-00062723 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
November 2015 |
| Est. completion date |
June 30, 2017 |
Study information
| Verified date |
January 2022 |
| Source |
University of Maryland, Baltimore |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Traumatic brain injury (TBI) affects 1.5 million patients per year in the United States,
resulting in more than 50,000 deaths and more than 230,000 hospitalizations annually.
Approximately 90,000 of these patients will suffer permanent impairment and more than half
will experience short-term disability.
Secondary injury processes play a critical role in the development of ischemia after trauma
to the central nervous system and occur hours-to-days after the primary insult. Ischemia can
lead to cerebral infarction or stroke. Ischemia has been described as the single most
important secondary insult and has been identified histologically in approximately 90% of
patients who die following closed head injury. Several factors resulting in post-traumatic
cerebral ischemia have been identified: increased intracranial pressure (ICP), systemic
arterial hypotension, and cerebral vasospasm. Cerebral vasospasm has been described as a
sustained arterial narrowing. Clinically, the onset of new or worsening neurological symptoms
is the most reliable indicator of cerebral vasospasm following a ruptured cerebral aneurysm.
However, cerebral vasospasm is often unrecognized in patients suffering from moderate to
severe TBI. These patients frequently have altered mental status due to the primary brain
injury. In addition, they require narcotics for their pain and paralytics and/or sedatives
while on a mechanical ventilator for airway protection. Thus, relying on the neurological
exam to observe deteriorating neurological signs consistent with post-traumatic vasospasm
(PTV) is reliable. While the etiology and outcome of patients with vasospasm secondary to
ruptured aneurysm is well documented, the clinical significance of PTV after TBI is unknown.
A better understanding of the role of cerebral autoregulation in the development of cerebral
vasospasm could provide the answer. This proposal is for a pilot observational study
describing the association of the impairment of cerebral autoregulation as measured by near
infrared spectroscopy (NIRS) with the development of clinically significant vasospasm in
patients with moderate to severe TBI. The information will serve as preliminary data for
further study.
Description:
Primary Objectives: 1. To determine if impaired cerebral autoregulation as measured by NIRS
is associated with clinically significant vasospasm in patients with moderate to severe TBI;
2. To determine the sensitivity and specificity of NIRS in detecting clinically significant
vasospasm with Transcranial Doppler (TCD) ultrasound followed by CT brain angiography and
diffusion-weighted brain MRI as the gold standard . Secondary Objectives: 1. To determine the
relationship between impaired cerebral autoregulation and outcomes; 2. To determine the
relationship between impaired cerebral autoregulation, clinically significant vasospasm and
outcomes
Clinical observations The subject will be continuously monitored with INVOS NIRS system
within the first 24 hours after admission up to 7 days while the subject is still in the STC.
If decreased cerebral oxygenation is detected by NIRS, TCDs will be offered to the family and
considered part of routine clinical care. If vasospasm is detected by TCD, CT brain
angiography will be offered to the family for angiographic confirmation and considered part
of routine clinical care. If vasospasm is confirmed by CT brain angiography,
diffusion-weighted MRI will be offered to the family to evaluate for cerebral
ischemia/infarction and considered part of routine clinical care.
Laboratory evaluations All patients will have at least twice daily measurements of serum
electrolytes, blood counts, arterial blood gases, and coagulation profile as per our standard
of care. Culture results will be recorded. No tests or procedure will be ordered for research
purposes only.
Patient Management All enrolled patients will be admitted to the Neurotrauma Critical Care
Unit (NTCC) and be jointly managed by the Trauma, Critical Care and Neurosurgical services.
All patients will be managed utilizing the STC Institutional Severe Traumatic Brain Injury
Management Algorithm which is based on the Brain Trauma Foundation Guidelines for the
Management of Severe Traumatic Brain Injury. Other consults will be obtained as clinically
indicated.
Questionnaires / Assessment tools Functional outcome using the Extended Glasgow Outcome Scale
(GOS-E) will be assessed in the STC Outpatient Clinic as part of their standard of care. An
early functional outcome assessment will be obtained if the GOS-E form is completed at the
STC Outpatient Clinic within 6 weeks post hospital discharge day. A mid functional outcome
assessment will be obtained if the GOS-E form is completed at the STC Outpatient Clinic 6
weeks to 3 months post hospital discharge day. A late functional outcome assessment will be
obtained if the GOS-E form is completed at the STC Outpatient Clinic 3 months to 6 months
post hospital discharge day. Finally, a very late functional outcome assessment will be
obtained if the GOS-E form is completed at the STC Outpatient Clinic more than 6 months
post-hospital discharge day.
STATISTICAL CONSIDERATIONS / ANALYSIS OF DATA The goal of this pilot study is to determine if
impaired cerebral autoregulation as measured by NIRS is associated with the development of
clinically significant vasospasm in patients with moderate to severe TBI. By enrolling 100
patients in the study, it is expected to estimate the correlation to within 0.098 with a
probability of at least 95%. In this study, all primary and secondary outcomes may be
classified into two categories: binary and continuous. In the first step, quantitative
descriptive statistics will be used initially to study the characteristics of patients and
the association between clinical outcomes (e.g. vasospasm) and various demographic and
clinicopathologic variables such as age, gender and injury severity scores. For binary data,
chi-square and Fisher's exact tests will be used to identify differences. For continuous
variables, t-tests and analysis of variance (ANOVA) will be used to determine the significant
association. These univariate tests will be done at a significance level of 0.05. In addition
to constructing 95% confidence interval for the correlation of impaired cerebral
autoregulation as measured by NIRS and clinically significant vasospasm, the investigators
will also explore potential risk factors associated with impaired cerebral autoregulation and
impaired cerebral autoregulation associated with vasospasm. To this end, the correlation will
be analyzed using the logistic regression model with various demographic and
clinicopathologic variables as independent variables. The stepwise regression procedure will
be used for identifying potential risk factors for the incidence of vasospasm. To evaluate
the validity of NIRs as an assessment method of vasospasm, the investigators will measure the
agreement between TCD and NIRS by using kappa statistics.
