Optic Nerve Ultrasound in Severe Traumatic Injury (ONUS-TBI)

January 4, 2021 updated by: Venkatakrishna Rajajee, University of Michigan

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Actual)

117

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
      • New Delhi, India
        • All India Institute Of Medical Sciences (AIIMS)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with severe TBI in the neurotrauma ICU who meet inclusion/exclusion.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Optic nerve ultrasound
Optic nerve sheath diameter (ONSD) measurement will be performed in subjects with concomitant measurement of Intracranial Pressure (ICP) from an invasive ICP monitor. The operator measuring ONSD will be blinded to concomitant ICP.
Device: Optic nerve ultrasound
Measurement of ONSD with concomitant invasive ICP measurement will be performed at enrollment and at least daily for a total of 7 days. Additional measurements of ONSD may be performed at any time following any decline in Glasgow Coma Scale (GCS) score by 2+ points during the 7 day period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intracranial Pressure (ICP) >25mmHg
Time Frame: Days 1-7
Accuracy of ONSD measurement (index test) compared to the reference standard- ICP>25mmHg on concomitant invasive monitoring
Days 1-7

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Therapeutic Intensity Level (TIL)
Time Frame: Assessed at time of discharge from the neurotrauma intensive care unit- Average expected to be about 7 days
Highest Therapeutic Intensity Level attained during the ICU admission
Assessed at time of discharge from the neurotrauma intensive care unit- Average expected to be about 7 days
In-Hospital Mortality
Time Frame: At Discharge from inpatient admission- Average expected to be about 30 days
All-cause mortality during the inpatient admission
At Discharge from inpatient admission- Average expected to be about 30 days
Poor functional outcome at discharge- Glasgow Outcome Scale <4
Time Frame: At Discharge from inpatient admission- Average expected to be about 30 days
Moderate or low disability at the time of discharge
At Discharge from inpatient admission- Average expected to be about 30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Michigan

Collaborators

All India Institute of Medical Sciences, New Delhi
National Institutes of Health (NIH)
National Institute for Biomedical Imaging and Bioengineering (NIBIB)

Investigators

  • Principal Investigator: Venkatakrishna (Krishna) Rajajee, MD, University of Michigan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2016

Primary Completion (Actual)

December 1, 2020

Study Completion (Actual)

December 1, 2020

Study Registration Dates

First Submitted

November 19, 2015

First Submitted That Met QC Criteria

November 25, 2015

First Posted (Estimate)

December 1, 2015

Study Record Updates

Last Update Posted (Actual)

January 5, 2021

Last Update Submitted That Met QC Criteria

January 4, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HUM00092614
  • IEC/NP-407/14.11.2014, RP (Other Identifier: All India Institute of Medical Sciences (AIIMS))
  • R03EB019352 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Traumatic Brain Injury

Clinical Trials on Optic nerve ultrasound

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Italy

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe