Brain Injuries, TraumaticCerBio-mTBINCT06069674
Use of Cerebral Biomarkers in Minor Traumatic Brain Injury in the Emergency Unit
An observational study of Brain Injuries, Traumatic and Trauma, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
Trial summary
The use of serum biomarkers in the setting of the emergency department (ED) has been well characterized over the years as an adjunctive tool for the clinician in the setting of complex decision making. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Injuries, Traumatic, Trauma, Trauma, Nervous System
- What is being tested?
- Serum dosage of GFAP and UCH-L1
- How many people
- 1,510 participants
- Where
- 1 siteItaly
- Study dates
- 1 Oct 2022to 30 Mar 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The study population will include all non-pregnant patients, who are > 18 y.o. and meet the pre-specified inclusion criteria. We will enroll patients who present to our ED with mTBI and who undergo a venous blood sample and serial brain CT scans as part of their standard emergency care according to the present intra-hospital guidelines and the choice of the attending physician
Who may be able to join
- Patients ≥18 years old;
- Patients who present to the ED within 4 hours since a traumatic event and reporting mTBI.
- Patients who own risk factors for delayed intracranial bleeding, defined as: history of anticoagulant therapy (VKA or DOACs) or known coagulopathy.
- Patients who undergo serial CT scan during the emergency evaluation as part of the standard ED care and if a sample of venous blood will be obtained at the moment of the visit.
- Signed written informed consent to study participation and personal data treatment.
Who cannot join
- Age <18 years old;
- Pregnant women;
- Refusal to sign written informed consent to study participation and personal data treatment.
Trial locations and contacts
1 site in 1 country.
Gianluca Tullo, Dr. contact
Italy1 site, 1 recruiting
- Recruiting
Fondazione Policlinico Universitario "A. Gemelli" IRCCS
Roma, 00168
Gianluca Tullo, Dr., 3926595850 ext. +39, gianlucatullo@gmail.com
About this study
The use of serum biomarkers in the setting of the emergency department (ED) has been well characterized over the years as an adjunctive tool for the clinician in the setting of complex decision making. In this regard, the serum dosage of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) has been evaluated in a series of successful multicenter prospective studies as a potentially useful marker of, respectively, glial and neuronal damage in the setting of mild traumatic brain injury (mTBI), which is defined as a brain injury (concussion) secondary to trauma with a GCS (Glasgow coma scale) score of 13-15. It seems that both markers are detectable in serum less than 1 hour after the traumatic event, with highest levels appearing at around 2 hours, and are capable of distinguishing between patients with traumatic brain injury from those without acute brain injury after trauma. Furthermore, they seem to possess a high negative predictive value for detection of intracranial injuries at head CT-scan as well as the need of neurosurgical intervention after head trauma.
Mild traumatic brain injury is one of the most frequent chief-complaints for patients presenting to emergency departments worldwide. At present, head CT scan is the gold standard diagnostic test for the identification of potentially life-threatening intra-cranial injuries. Although effective in the identification of serious lesions which might require neurosurgical intervention or in-hospital prolonged observation, the extensive use of head CT scan in mTBI has been questioned due to the potential risks related to radiation exposure, as well as unnecessary deployment of ED resources and increased costs, considering that the prevalence of CT-detected intra-cranial injury in mTBI is around 5-10%.
Read more
For this reason, a number of international clinical guidelines suggest several Clinical Decision Rules (CDR) and algorithms to guide the clinician in the correct management of these patients, in particular in the difficult feat of identifying those patients who don't need to perform neuroradiological evaluation (CT scan or MRI) in the setting of the ED, without the risk to overlook potentially fatal brain injuries.
The adjunctive role of these biomarkers has been well characterized in the setting of mTBI. It seems they correlate well with neurological damage as well as with the presence of CT abnormalities, and it seems that they might perform better than clinical evaluation alone.
Nonetheless, according to current international guidelines and several systematic reviews and meta-analysis, patients who present with mTBI and risk factors for bleeding and delayed bleeding (such as known coagulopathy, patients on blood thinners or advanced age), need to perform CT scan plus clinical observation or even serial CT scans when the risk of delayed bleeding is considered to be high according to clinical evaluation of the ED physician and according to local standard-of-care and clinical practice. The execution of serial CT scans can be time consuming, expensive for the health-care services, and might pose a significant radiological risk for patients; furthermore, this risk might be unjustified considering that the prevalence of development of late intra-cranial bleeding in patients with risk factors who perform a second head CT scan during observation in the ED is considered to be around 2%.
Nonetheless, in this category of patients, clinical observation and the repetition of a second head CT scan is felt to be the safest course of action for patients in order not to overlook potentially fatal injuries.
Ideally, a clinical decision algorithm which takes into consideration a serum biomarker with a high negative predictive value for brain injury might aid the clinician to reduce the number of useless CT scans, therefore reducing the observation time in the ED as well as the exposure to ionizing radiations for the patients, while not increasing the number of missed delayed bleedings.
At present, the role of GFAP and UCH-L1 in the risk stratification of patients with risk factors for delayed cerebral bleeding after mTBI has not been evaluated yet.
Read the detailed description
Study design Ambispective observational study without drug nor device.
Population The study population will include all non-pregnant patients, who are > 18 y.o. and meet the pre-specified inclusion criteria. We will enroll patients who present to our ED with mTBI and who undergo a venous blood sample and serial brain CT scans as part of their standard emergency care according to the present intra-hospital guidelines and the choice of the attending physician.
Study duration The duration of the study will be of 18 months starting from the approval of the present protocol by the local Ethics Committee of Fondazione Policlinico Universitario Agostino Gemelli IRCCS of Rome. Retrospectively enrolled patients will cover the period from October 2022 up to approval of the protocol, date in which the prospective enrollment will start. The enrolment phase will last 12 months, whilst the following 6 will be dedicated to data extraction, statistical analysis and scientific reporting.
Variables and procedures Retrospective data will be retrieved from our healthcare electronic system for all patients who presented to the ED with the inclusion criteria. In this case, patients will be contacted by phone to provide informed consent. Prospectively enrolled patients will be selected by the attending physician at the moment of the first visit if eligible and written informed consent will be obtained. Patients will be enrolled if they undergo serial CT scans during the emergency evaluation as part of the standard ED care and if a sample of venous blood will be obtained at the moment of the visit. Serum analysis will be performed and dosage of GFAP and UCH-L1 obtained.
The collected variables will cover the following data:
- Demographic and anamnestic data (age, gender, BMI, past comorbidities, etc…);
- Description of the traumatic event and the time elapsed from the event to the first medical evaluation and blood sample;
- Clinical presentation at the moment of the first medical evaluation (including vital parameters and Glasgow Coma Scale);
- Result of the head CT scans performed during the ED visit, as well as the time at which they are performed. The result will be considered as a categorical variable, positive vs negative CT scan, where positive will considered any detected traumatic anomaly regardless of the severity of the injury;
- Serum dosage of GFAP and UCH-L1 obtained at the moment of the visit;
- Duration of ED visit;
Complications during the ED stay:
- Neurological deterioration, defined as a decrease in GCS with respect to the arrival;
- Need for neurosurgical consultation;
- Development of seizures;
- Emergent neurosurgical intervention: craniotomy, hematoma evacuation, need for invasive intra-cranial pressure monitoring, etc…
- Need for emergent airway management due to coma;
- Need for ICU admission;
- Death for any reason.
- Conditions
- Brain Injuries, Traumatic, Trauma, Trauma, Nervous System
- Being tested
- Serum dosage of GFAP and UCH-L1
- Medical subject headings
- Brain Injuries, Traumatic, Wounds and Injuries, Trauma, Nervous System
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Serum dosage of GFAP and UCH-L1Diagnostic test
blood test execution as per usual care in the ED
What is being measured
The primary outcome is the main question the study is designed to answer.
Sensitivity of Biomarkers
Sensitivity of the two pre-specified serum biomarkers for the detection of CT scan abnormalities in patients who present to the ED with mTBI and risk factors for delayed bleeding.
Measured: 30 days
Secondary outcomes (2)
Negative predictive value of Biomarkers
Negative predictive value of the two pre-specified serum biomarkers for the detection of CT scan abnormalities in patients who present to the ED with mTBI and risk factors for delayed bleeding
Measured: 30 days
Correlation of biomarkers with composite clinical outcome
- To evaluate the correlation of serum biomarkers with the composite outcome of patients (i.e. composite of neurosurgical consultation, neurological deterioration defined as decrease of GCS during ED observation, development of epileptic seizures, need for neurosurgical intervention (including craniotomy, hematoma evacuation, need for invasive monitoring of intra-cranial pressure), need of airway management and/or ICU admission, death for any reason), as well as single components
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2023
- Study start1 Oct 2022
- Primary completion31 Oct 2023 (estimated)
- Study completion30 Mar 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Brain Injuries, TraumaticStudies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,510 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, COVINO MARCELLO, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06069674
- Sponsor's protocol ID
- 5571
- Acronym
- CerBio-mTBI
- Status last verified
- Oct 2023
- First submitted
- 19 May 2023
- Last updated
- 6 Oct 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Spaziani G, Rozzi G, Baroni S, Napoli G, De Ninno G, Polla DD, Bonadia N, De Matteis G, Piccioni A, Pepa GMD, Urbani A, Gasbarrini A, Franceschi F, Covino M. Prognostic value of GFAP and UCHL-1 biomarkers in high-risk mild traumatic brain injury: A prospective longitudinal study of short- and long-term outcomes. Am J Emerg Med. 2026 Mar;101:41-47. doi: 10.1016/j.ajem.2025.12.021. Epub 2025 Dec 22.
PubMed 41455435
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Cerebral Biomarkers in Minor Traumatic Brain Injury in the Emergency Unit
- ClinicalTrials.gov ID
- NCT06069674
- Acronym / sponsor ID
- CerBio-mTBI / 5571
- Conditions
- Brain Injuries, Traumatic, Trauma, Trauma, Nervous System
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 1,510 participants (estimated)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Study start
- 1 Oct 2022 (actual)
- Primary completion
- 31 Oct 2023 (estimated)
- Study completion
- 30 Mar 2024 (estimated)
- First posted
- 6 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The use of serum biomarkers in the setting of the emergency department (ED) has been well characterized over the years as an adjunctive tool for the clinician in the setting of complex decision making. In this regard, the serum dosage of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) has been evaluated in a series of successful multicenter prospective studies as a potentially useful marker of, respectively, glial and neuronal damage in the setting of mild traumatic brain injury (mTBI), which is defined as a brain injury (concussion) secondary to trauma with a GCS (Glasgow coma scale) score of 13-15. It seems that both markers are detectable in serum less than 1 hour after the traumatic event, with highest levels appearing at around 2 hours, and are capable of distinguishing between patients with traumatic brain injury from those without acute brain injury after trauma. Furthermore, they seem to possess a high negative predictive value for detection of intracranial injuries at head CT-scan as well as the need of neurosurgical intervention after head trauma.
Mild traumatic brain injury is one of the most frequent chief-complaints for patients presenting to emergency departments worldwide. At present, head CT scan is the gold standard diagnostic test for the identification of potentially life-threatening intra-cranial injuries. Although effective in the identification of serious lesions which might require neurosurgical intervention or in-hospital prolonged observation, the extensive use of head CT scan in mTBI has been questioned due to the potential risks related to radiation exposure, as well as unnecessary deployment of ED resources and increased costs, considering that the prevalence of CT-detected intra-cranial injury in mTBI is around 5-10%.
For this reason, a number of international clinical guidelines suggest several Clinical Decision Rules (CDR) and algorithms to guide the clinician in the correct management of these patients, in particular in the difficult feat of identifying those patients who don't need to perform neuroradiological evaluation (CT scan or MRI) in the setting of the ED, without the risk to overlook potentially fatal brain injuries.
The adjunctive role of these biomarkers has been well characterized in the setting of mTBI. It seems they correlate well with neurological damage as well as with the presence of CT abnormalities, and it seems that they might perform better than clinical evaluation alone.
Nonetheless, according to current international guidelines and several systematic reviews and meta-analysis, patients who present with mTBI and risk factors for bleeding and delayed bleeding (such as known coagulopathy, patients on blood thinners or advanced age), need to perform CT scan plus clinical observation or even serial CT scans when the risk of delayed bleeding is considered to be high according to clinical evaluation of the ED physician and according to local standard-of-care and clinical practice. The execution of serial CT scans can be time consuming, expensive for the health-care services, and might pose a significant radiological risk for patients; furthermore, this risk might be unjustified considering that the prevalence of development of late intra-cranial bleeding in patients with risk factors who perform a second head CT scan during observation in the ED is considered to be around 2%.
Nonetheless, in this category of patients, clinical observation and the repetition of a second head CT scan is felt to be the safest course of action for patients in order not to overlook potentially fatal injuries.
Ideally, a clinical decision algorithm which takes into consideration a serum biomarker with a high negative predictive value for brain injury might aid the clinician to reduce the number of useless CT scans, therefore reducing the observation time in the ED as well as the exposure to ionizing radiations for the patients, while not increasing the number of missed delayed bleedings.
At present, the role of GFAP and UCH-L1 in the risk stratification of patients with risk factors for delayed cerebral bleeding after mTBI has not been evaluated yet.
Detailed description
Study design Ambispective observational study without drug nor device.
Population The study population will include all non-pregnant patients, who are > 18 y.o. and meet the pre-specified inclusion criteria. We will enroll patients who present to our ED with mTBI and who undergo a venous blood sample and serial brain CT scans as part of their standard emergency care according to the present intra-hospital guidelines and the choice of the attending physician.
Study duration The duration of the study will be of 18 months starting from the approval of the present protocol by the local Ethics Committee of Fondazione Policlinico Universitario Agostino Gemelli IRCCS of Rome. Retrospectively enrolled patients will cover the period from October 2022 up to approval of the protocol, date in which the prospective enrollment will start. The enrolment phase will last 12 months, whilst the following 6 will be dedicated to data extraction, statistical analysis and scientific reporting.
Variables and procedures Retrospective data will be retrieved from our healthcare electronic system for all patients who presented to the ED with the inclusion criteria. In this case, patients will be contacted by phone to provide informed consent. Prospectively enrolled patients will be selected by the attending physician at the moment of the first visit if eligible and written informed consent will be obtained. Patients will be enrolled if they undergo serial CT scans during the emergency evaluation as part of the standard ED care and if a sample of venous blood will be obtained at the moment of the visit. Serum analysis will be performed and dosage of GFAP and UCH-L1 obtained.
The collected variables will cover the following data:
- Demographic and anamnestic data (age, gender, BMI, past comorbidities, etc…);
- Description of the traumatic event and the time elapsed from the event to the first medical evaluation and blood sample;
- Clinical presentation at the moment of the first medical evaluation (including vital parameters and Glasgow Coma Scale);
- Result of the head CT scans performed during the ED visit, as well as the time at which they are performed. The result will be considered as a categorical variable, positive vs negative CT scan, where positive will considered any detected traumatic anomaly regardless of the severity of the injury;
- Serum dosage of GFAP and UCH-L1 obtained at the moment of the visit;
- Duration of ED visit;
Complications during the ED stay:
- Neurological deterioration, defined as a decrease in GCS with respect to the arrival;
- Need for neurosurgical consultation;
- Development of seizures;
- Emergent neurosurgical intervention: craniotomy, hematoma evacuation, need for invasive intra-cranial pressure monitoring, etc…
- Need for emergent airway management due to coma;
- Need for ICU admission;
- Death for any reason.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study population will include all non-pregnant patients, who are > 18 y.o. and meet the pre-specified inclusion criteria. We will enroll patients who present to our ED with mTBI and who undergo a venous blood sample and serial brain CT scans as part of their standard emergency care according to the present intra-hospital guidelines and the choice of the attending physician
Key inclusion criteria (5 listed)
- Patients ≥18 years old;
- Patients who present to the ED within 4 hours since a traumatic event and reporting mTBI.
- Patients who own risk factors for delayed intracranial bleeding, defined as: history of anticoagulant therapy (VKA or DOACs) or known coagulopathy.
- Patients who undergo serial CT scan during the emergency evaluation as part of the standard ED care and if a sample of venous blood will be obtained at the moment of the visit.
- Signed written informed consent to study participation and personal data treatment.
Key exclusion criteria (3 listed)
- Age <18 years old;
- Pregnant women;
- Refusal to sign written informed consent to study participation and personal data treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Serum dosage of GFAP and UCH-L1blood test execution as per usual care in the ED | Diagnostic test | – |
Primary outcome
Sensitivity of Biomarkers
Time frame: 30 days
Sensitivity of the two pre-specified serum biomarkers for the detection of CT scan abnormalities in patients who present to the ED with mTBI and risk factors for delayed bleeding.
2 secondary outcomes
Negative predictive value of Biomarkers
Time frame: 30 days
Correlation of biomarkers with composite clinical outcome
Time frame: 30 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2023.
- Derived from this study: PubMed 41455435Spaziani G, Rozzi G, Baroni S, Napoli G, De Ninno G, Polla DD, Bonadia N, De Matteis G, Piccioni A, Pepa GMD, Urbani A, Gasbarrini A, Franceschi F, Covino M. Prognostic value of GFAP and UCHL-1 biomarkers in high-risk mild traumatic brain injury: A prospective longitudinal study of short- and long-term outcomes. Am J Emerg Med. 2026 Mar;101:41-47. doi: 10.1016/j.ajem.2025.12.021. Epub 2025 Dec 22.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gianluca Tullo, Dr. contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Brain Injuries, Traumatic and Trauma, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Marcello Covino, Dr. (0630153162 ext. +39, marcello.covino@policlinicogemelli.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sensitivity of Biomarkers (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06069674, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2023.