Clinical trial NCT02618226: Optic Nerve Ultrasound in Severe Traumatic Injury
Official title: Diagnostic Accuracy of Optic Nerve Ultrasound for the Detection of Intracranial Hypertension and Prediction of Therapeutic Intensity Level and Mortality Following Severe Traumatic Brain Injury (ONUS-TBI): a Prospective Blinded Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Traumatic Brain Injury
Intracranial Hypertension
Keywords: Traumatic Brain Injury
TBI
Optic nerve ultrasound
ONUS
Intracranial pressure
ICP
Intracranial hypertension
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: All India Institute of Medical Sciences
name: National Institutes of Health (NIH)
name: National Institute for Biomedical Imaging and Bioengineering (NIBIB)
First posted: 2015-12-01
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with severe TBI in the neurotrauma ICU who meet inclusion/exclusion.

Brief summary: Prospective study of diagnostic accuracy of optic nerve sheath diameter measurement (index study) in traumatic brain injury with simultaneous invasive intracranial pressure monitoring as the reference standard.

Detailed description: Background and Rationale:

Traumatic brain injury (TBI) is a public health problem of epidemic proportions both in the United States (US) and India. Trauma is estimated to be the leading cause of death in the age group 20-40 years in India and accounts for 2-3% loss of gross domestic product (GDP) every year. The incidence of TBI in India is among the highest in the world and is rapidly rising along with a rapid increase in automobile density. Compared to the United States, poor outcomes reported following TBI in India can be attributed to several factors including underdeveloped pre-hospital care, problems with transport to appropriate medical attention, limited availability of centers for trauma care, lack of appropriate training and expertise and lack of application of standards of TBI care widely accepted in the developed world. Over the last two decades the management of TBI in the US and Europe has centered on the guidelines developed by the Brain Trauma Foundation (BTF). Severe TBI, defined by a Glasgow Coma Scale \<8, carries the worst prognosis, with a mortality of 30-40% in reports from India compared to 10-20% in the US. Monitoring of the Intracranial Pressure (ICP) is an integral part of the management of severe TBI, with the BTF recommending monitoring of ICP in appropriate candidates and maintenance of ICP at \<20-25mmHg using a range of therapeutic options. The rationale for this recommendation lies in the fact that ICP\>20mmHg is associated with clinical neurological decline and that Cerebral Perfusion Pressure \[Mean Arterial Pressure (MAP) - ICP\] \<50mmHg is associated with worse neurological outcomes. Importantly, studies examining TBI have demonstrated an increase in 2-week mortality with non-use of ICP monitoring. Moreover adherence to guidelines on the management of ICP, including treatment of ICP\>25mmHg, have been associated with a significant decline in mortality in New York state.

While widely accepted as the standard of care in the US, invasive ICP is not considered the standard of care in the developing world. Rather, clinical equipoise is considered to exist on the best way to measure ICP in these regions. A randomized controlled trial performed in Bolivia and Ecuador comparing an invasive ICP monitoring-based management protocol with a management protocol without invasive monitoring demonstrated no difference in neurological outcomes. While this trial may have been confounded by other, important differences between the interventions in both arms, it does illustrate the fact that invasive monitoring is not the current standard of care in the developing world. While the appropriate role and indications for invasive ICP monitoring in the developing world may be a matter of debate, the strong association between appropriate ICP management and mortality observed in other studies suggests that an urgent, unmet need exists for a low-cost, low-risk, non-invasive, point-of-care alternative to invasive monitoring for the detection of life-threatening increases in ICP following TBI. While the need for such a tool may be greatest in the developing world, where invasive monitoring is mostly unavailable, a validated non-invasive ICP monitor would also be of great value in the US, in potentially decreasing the risks of intracranial placement as well as the costs of invasive monitoring. While Optic Nerve Ultrasound (ONUS) is a promising noninvasive tool for the detection of life threatening intracranial hypertension, it is neither a continuous nor a quantitative measure of ICP and is unlikely to entirely replace invasive monitoring. The greatest potential value of a noninvasive diagnostic tool such as ONUS may be to function as a screening tool to permit early initiation of life-saving treatment measures and to decrease the burden of risk and expense associated with invasive monitoring. As a screening tool the sensitivity for the detection of intracranial hypertension will need to be high, while a moderate specificity may be acceptable, since a noninvasive measurement suggesting an increased likelihood of elevated ICP will likely lead to the placement of an invasive ICP monitor to follow the response to therapeutic intervention. Early identification of patients at risk of death from elevated ICP using noninvasive assessment tools may permit providers to both initiate treatment earlier and target limited resources toward these high-risk individuals.

Objective:

Aim 1: To determine the optimal optic nerve sheath diameter (ONSD) measurement for the detection of raised intracranial pressure (ICP) in Indian patients using Receiver Operating Characteristic (ROC) curves, with emphasis on a cut-off with high sensitivity and acceptable specificity, as appropriate for a screening tool.

Hypothesis- An ONSD threshold will be identified to maximize the true positive rate (\>0.98) with acceptable specificity (\>80%) for the detection of elevated ICP (\>25mmHg).

Aim 2: To evaluate whether the optic nerve sheath diameter predicts Therapeutic Intensity Level, in-hospital mortality and discharge functional outcome following severe traumatic brain injury.

Hypothesis- The highest measured optic nerve sheath diameter within the first 48 hours in a patient with TBI will be associated with the Therapeutic Intensity Level, mortality during hospitalization and discharge functional outcome.

Study setting: The Jai Prakash Narayan Apex Trauma Center (JPNATC) at the All India Institute of Medical Sciences (AIIMS), New Delhi, is the apex referral center for TBI in New Delhi as well as from much of the rest of the country. It has 30 triage and 36 ICU beds, with 300-600 severe TBI admissions every year.

Eligibility criteria: Inclusion Criteria:

1. Adult (age\>18 years) patients
2. Severe TBI (GCS\<8)
3. First measurement feasible \<48 hours from time of injury
4. Clinical decision has been made to place an invasive ICP monitor, based on the recommendations of the Brain Trauma Foundation.

I. GCS\<8 and Abnormal CT brain OR II. GCS\<8 and Normal CT brain PLUS any 2 of the following

1. Age\>40
2. Systolic blood pressure\<90
3. Unilateral or Bilateral Posturing

Exclusion Criteria:

1. Patient not expected to survive \>48 hours from the time of enrollment
2. Known injury to the globe of the eye or the optic nerve
3. Therapeutic Intensity Level 3 or 4 attained before ONSD measurement can be performed.

Primary outcomes:
measure: Intracranial Pressure (ICP) >25mmHg
timeFrame: Days 1-7
Secondary outcomes:
measure: Therapeutic Intensity Level (TIL)
timeFrame: Assessed at time of discharge from the neurotrauma intensive care unit- Average expected to be about 7 days
measure: In-Hospital Mortality
timeFrame: At Discharge from inpatient admission- Average expected to be about 30 days
measure: Poor functional outcome at discharge- Glasgow Outcome Scale <4
timeFrame: At Discharge from inpatient admission- Average expected to be about 30 days
Other outcomes:
Locations:
city: New Delhi
country: India
facility: All India Institute of Medical Sciences (AIIMS)
Study officials:
affiliation: University of Michigan
name: Venkatakrishna (Krishna) Rajajee, MD
role: PRINCIPAL_INVESTIGATOR
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