Evaluation of Patients Affected by Traumatic and Hypoxic-ischemic Brain Injury (PETRA)

March 6, 2025 updated by: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Clinical and Epidemiological Evaluation of Patients Affected by Traumatic and Hypoxic-ischemic Brain Injury

According to the World Health Organization, perinatal asphyxia is the leading cause of severe neurological disabilities and the second leading cause of neonatal death among term infants, with an incidence of 3.94-5.12 per 1,000 live births. Perinatal asphyxia leads to neonatal hypoxic-ischemic encephalopathy, which remains a common cause of neonatal death and long-term disabilities, affecting 1.5-3 per 1,000 live births in developed countries and up to 26 per 1,000 live births in developing countries. This condition is characterized by altered levels of consciousness or manifests with seizures, often associated with difficulties in initiating and maintaining breathing, as well as depression of tone and reflexes. Currently, therapeutic hypothermia is the standard treatment for neonates with moderate to severe hypoxic-ischemic encephalopathy; however, it does not provide complete neuroprotection and is only partially effective. Therefore, new treatments with good therapeutic windows are urgently needed to ensure the best possible preservation of neurological tissue for patients exposed to hypoxic-ischemic insult. Traumatic brain injury is a common cause of morbidity and mortality among children and young adults in developed countries. The incidence of traumatic brain injury has increased in recent years, yet the prognosis for these patients has not substantially changed. In recent studies the key intermediary role of the immune system and neuroinflammation has been proposed to explain the pathophysiology of traumatic brain injury, both in the acute phase and in the long term. Indeed, neuroinflammatory processes can persist for several months, contributing to chronic alterations and accelerating brain aging in patients with post-traumatic brain injury. Currently, therapies that have shown promising results in patients with post-traumatic brain injuries are unfortunately still limited, especially in the context of severe traumatic brain injury. Thus, there is an urgent need for new treatments with a broader therapeutic window that can counteract early and chronic pathophysiological events.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

According to the World Health Organization, perinatal asphyxia is the leading cause of severe neurological disabilities and the second leading cause of neonatal death among term infants, with an incidence of 3.94-5.12 per 1,000 live births. Perinatal asphyxia leads to neonatal hypoxic-ischemic encephalopathy, which remains a common cause of neonatal death and long-term disability, affecting 1.5-3 per 1,000 live births in developed countries and up to 26 per 1,000 live births in developing countries. Neonatal hypoxic-ischemic encephalopathy represents a clinical syndrome characterized by neurological function disturbances in the early days of life for infants born after the 35th week of gestation. This condition is marked by altered consciousness levels or seizures, often associated with difficulties in initiating and maintaining breathing, as well as depression of tone and reflexes. There are many potential causes of neonatal encephalopathy, the most common being a hypoxic-ischemic insult. Other causes include infections, perinatal stroke, intracranial hemorrhage, congenital brain malformations, and metabolic and genetic syndromes. Neonatal hypoxia-ischemia is the most common cause of death and disability in newborns and is often associated with persistent motor, sensory, and cognitive deficits. The pathophysiology following neonatal hypoxic-ischemic brain injury is complex and unfolds in several stages. Hypoxic-ischemic encephalopathy evolves through distinct phases: after the initial hypoxic-ischemic event, there is an acute damage phase characterized by anaerobic metabolism, oxidative stress, excitotoxicity, and necrosis of neuronal cells. This phase is followed by a latency period lasting 1-6 hours, marked by neuroinflammation and activation of apoptotic cascades. Within 6-15 hours, a secondary phase develops characterized by cytotoxic edema, excitotoxicity, and cerebral hyperperfusion. Finally, the last phase occurs in the weeks or months following the injury and involves delayed cell death and remodeling of the damaged brain. Currently, therapeutic hypothermia is the standard care for neonates with moderate to severe hypoxic-ischemic encephalopathy. Hypothermia involves cooling the entire body to an internal temperature of 33.5 °C for 72 hours within 6 hours of birth. Scientific evidence indicates that therapeutic hypothermia inhibits key steps in the excitotoxic-oxidative cascade. This therapy improves neurological outcomes at 18 months and at 6 years of age, reducing mortality from 25% to 9% and disability from 20% to 16%, and is now recommended as standard care. However, it does not provide complete neuroprotection and is only partially effective. Even after treatment, there remains a high prevalence of neurological morbidity and mortality affecting 40-50% of surviving neonates undergoing therapeutic hypothermia. After hypothermia treatment, a significant percentage of neonates still develop long-term neurodisabilities. Therefore, it is essential to further optimize and enhance neonatal care. Additional neuroprotective interventions are currently being evaluated in randomized controlled trials, focusing on erythropoietin, allopurinol, topiramate, caffeine, melatonin, or stem cells. However, even experimental therapies have not yet proven effective in improving outcomes for these patients. Following hypoxic-ischemic injury, multiple pathophysiological events trigger secondary injuries. Therefore, the early blockade of these damage mechanisms could lead to a substantial long-term therapeutic effect. New treatments with good therapeutic windows are urgently needed to ensure the best possible preservation of neurological tissue for patients exposed to hypoxic-ischemic insult. Traumatic brain injury (TBI) is a common cause of morbidity and mortality among children and young adults in developed countries. The incidence of TBI has increased in recent years, but the prognosis for these patients has not changed substantially. Approximately 10% of patients with TBI present injuries that require hospitalization, and about 2% have fatal injuries. TBI occurs most frequently in very young children (ages 0 to 4) and in adolescents or young adults (ages 15 to 24), with a subsequent peak incidence in older adults. Post-traumatic brain injuries exhibit a complex pathophysiology, ranging from neuroinflammation and neurodegeneration to increased cerebral blood flow and blood-brain barrier permeability, leading to microvascular brain damage. Primary damage initiates a cascade of biochemical, metabolic, and inflammatory alterations that result in secondary damage associated with glutamatergic excitotoxicity, vascular dysfunction, calcium overload, and neuroinflammation. This primary injury rapidly triggers secondary injury that evolves over weeks or months. Recent studies have proposed the key role of immune system intermediaries and neuroinflammation to explain the pathophysiology of TBI, both acutely and long-term. Indeed, neuroinflammatory processes can persist for several months, thereby contributing to chronic alterations and an acceleration of brain aging in post-TBI patients. Currently, therapies that have shown promising results in patients with post-traumatic brain injuries are unfortunately still limited, especially in the management of severe TBI. Immediately after TBI, multiple pathophysiological events trigger the spread of secondary damage. Therefore, early blockade of one of the damage mechanisms could result in a substantial long-term therapeutic effect. New treatments with a broader therapeutic window are urgently needed to counteract early and chronic pathophysiological events.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Italy
    • Lazio
      • Roma, Lazio, Italy, 00168
        • Recruiting
        • Fondazione Policlinico Universitario A. Gemelli IRCCS, Pronto Soccorso Pediatrico
        • Contact:
        • Principal Investigator:
          • Antonio Chiaretti, prof
        • Sub-Investigator:
          • Antonio Gatto

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Patients aged 0-20 years diagnosed with brain damage post-severe head trauma or post-perinatal asphyxia.

Description

Inclusion Criteria:

  • Patients aged 0-20 years with brain damage due to severe traumatic brain injury or perinatal asphyxia evaluated at the Pediatric Emergency Department
  • Informed consent signed by the parents, the adult patient, or the legal guardian/representative.
  • Adult patients with psycho-cognitive impairments that affect their ability to provide consent, with prior acquisition of informed consent from the guardian/legal representative.

Exclusion Criteria:

  • Refusal to sign the informed consent
  • Patients with congenital malformations or genetic syndromes
  • Patients with neuromuscular diseases
  • Patients with encephalopathies of etiology other than severe head trauma or asphyxia
  • Patients with hemodynamically significant congenital heart diseases

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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Gross Motor Function Classification System
Time Frame: 2 years
Clinical assessment of the outcome of patients with traumatic and hypoxic-ischemic brain injury at least 2 years post-event, in terms of Analysis of motor deficits using the standardized scale "Gross Motor Function Classification System" where applicable. GMFCS is composed of 5 levels. Level I: Walks without limitations. Level V: Transported in a manual wheelchair.
2 years
Modified Ashworth Scale
Time Frame: 2 years
Clinical assessment of the outcome of patients with traumatic and hypoxic-ischemic brain injury at least 2 years post-event, in terms of Analysis of variations in muscle hypertonia and spasticity since the clinical event using the standardized scale "Modified Ashworth Scale" where applicable. Minimum Value: 0 This indicates no increase in muscle tone. Maximum Value: 4 This indicates that the affected part is rigid in flexion or extension.
2 years
Disability Rating Scale (DRS)
Time Frame: 2 years
Clinical assessment of the outcome of patients with traumatic and hypoxic-ischemic brain injury at least 2 years post-event, in terms of Analysis of the degree of disability using the standardized scale "Disability Rating Scale (DRS)" where applicable. Minimum value: 0 (indicates no disability). Maximum value: 30 (indicates an extreme vegetative state).
2 years
Pediatric Quality of Life Inventory generic core scale
Time Frame: 2 years
Clinical assessment of the outcome of patients with traumatic and hypoxic-ischemic brain injury at least 2 years post-event, in terms of Analysis of quality of life through administration of the standardized scale "Pediatric Quality of Life Inventory generic core scale" to the patient and caregiver where applicable. The minimum possible score is 0. The maximum possible score is 100. Higher scores indicate a better health-related quality of life.
2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pediatric Evaluation of Disability Inventory (PEDI)
Time Frame: 2 years
Two years post-brain injury (traumatic or hypoxic-ischemic), the Pediatric Evaluation of Disability Inventory (PEDI) assesses child's functional abilities in self-care, mobility, and social function, including their reliance on assistive devices like feeding tubes. PEDI provides a detailed profile of the child's abilities across specific domains, rather than a single minimum or maximum score.
2 years
Modified Tardieu Scale
Time Frame: 2 years
This study clinically evaluates the long-term outcomes (at least two years post-event) of chronic pharmacological therapies for spasticity, measured by the Modified Tardieu Scale (MTS), in patients with traumatic and hypoxic-ischemic brain injury. The MTS differentiates neural (spasticity) from non-neural (contracture) limitations by assessing muscle resistance at varying stretch speeds. This is graded on a scale, typically from 0 to 5, reflecting the intensity of the muscle's reaction to a fast stretch.
2 years
Communication Function Classification System
Time Frame: 2 years
Two years post-brain injury, this study evaluates everyday communication abilities using the Communication Function Classification System (CFCS). CFCS ranges from Level V (severely limited communication) to Level I (highly effective communication), assessing individuals' ability to exchange information across various settings and with different people.
2 years

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Antonio Chiaretti, Fondazione Policlinico Universitario A. gemelli, IRCCS

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 (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 15, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 31, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 31, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 9, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 6, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 25, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 6, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 7043 (CTEP)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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.

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