Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06069674 |
| Other study ID # |
5571 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
October 1, 2022 |
| Est. completion date |
March 30, 2024 |
Study information
| Verified date |
October 2023 |
| Source |
Fondazione Policlinico Universitario Agostino Gemelli IRCCS |
| Contact |
Marcello Covino, Dr. |
| Phone |
0630153162 |
| Email |
marcello.covino[@]policlinicogemelli.it |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical 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. 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.
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.
