The Multicenter Italian INCEPT (INfarto CErebrale Post-Traumatico) Study

Study Overview
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Brief Summary
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Traumatic brain injury (TBI) is a leading cause of death and disability worldwide (Ghajar, 2000). With an estimated annual incidence of up to 500 per 100,000 population and more than 200 hospital admissions per 100,000 admissions in Europe each year, TBI is a major challenge to public health (Lingsma, 2010). Mortality and morbidity after TBI depend on several factors, either associated with patients characteristics, the cause of TBI, the neurological and general severity and secondary brain insults, the structural brain alterations as diagnosed at brain computed tomography (CT) (Rosenfeld, 2012). The prognostic value of brain CT characteristics is well documented, including the status of basal cisterns, midline shift, the presence and type of intracranial lesions, and traumatic subarachnoid hemorrhage (Maas, 2008). Postraumatic cerebral ischemia, which includes functionally impaired yet still viable tissue, so-called ischemic penumbra, and irreversible cerebral infarction (PTCI), is frequent in patients who die after moderate or severe head trauma (Stocchetti, 2014). Evidence of antemortem occurrence of PTCI is limited to three single-center retrospective studies, reporting a varying prevalence of 1.9%, 8% and 19.1% (Mirvis, 1990; Marino, 2006; Tawil, 2008). Increased intracranial pressure (ICP), blunt cerebral vascular injury, need for craniotomy and treatment with recombinant activated factor VII, have been demonstrated to be risk factors for PTCI. In one study, PTCI was an independent risk factor for poor outcome after moderate or severe head trauma with a two-fold increase in mortality and severe disability (Marino, 2006). PTCI can be an important diagnosis in patients with significant TBI for various reasons. First, it might influence long-term outcome. Second, as an outcome that is measurable, and relevant to survival and lifestyle, PTCI could be used as an outcome measure in randomized controlled trials. Third, diagnosis of PTCI could be used as a standard diagnostic reference to validate early surrogate indicators of cerebral ischemia. The investigators therefore planned a multi-center prospective study to investigate the impact of PTCI on disability at hospital discharge, and on 6-month morbidity and mortality in a population of moderate and severe adult TBI patients. The investigators also evaluated the role of intracranial hypertension, decreased cerebral perfusion pressure, hypotension and other secondary ischemic insults in determining the appearance of PTCI.

Official Title
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Post Traumatic Cerebral Infarction Increases Mortality and Morbidity in Patients With Moderate or Severe Head Trauma. The Multicenter Italian INCEPT (INfarto CErebrale Post-Traumatico) Study

Conditions
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TBI (Traumatic Brain Injury), Stroke Acute

Intervention / Treatment
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* Other: posttraumatic cerebral infarction


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age >15 years old, with moderate or severe head trauma (GCS <14), admitted to ICU. Cases were classified as severe head injury (GCS score < 9), or moderate head injury (GCS score from 9 to 13). All patients recruited were monitored by means of invasive intracranial pressure (ICP), invasive arterial pressure monitoring, peripheral oxygen saturation, in accordance with published international and local guidelines Exclusion Criteria: age <16 years old, mild head trauma, absence of invasive ICP or invasive arterial pressure monitoring, dying patients, absence of brain stem reflexes.

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| TBI, no cerebral infarction<br>patients with moderate or severe brain injury that do not develop posttraumatic cerebral infarction | |
| TBI, posttraumatic cerebral infarction<br>patients with moderate or severe brain injury that develops posttraumatic cerebral infarction | Other: posttraumatic cerebral infarction<br>* the difference between groups refers to the developing of cerebral infarction after traumatic brain injury<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxford Handicap Scale (OHS) | The Oxford Handicap Scale evaluates the outcome as follow: 0 no symptoms, 1 minor symptoms, 2 minor handicap, 3 moderate handicap, 4 severe handicap, 5 death. Favourable outcome: 0-3; unfavourable outcome: 4-5 | patients will be evaluated at hospital discharge, an expected average of 3 weeks | 
| Glasgow Outcome Scale (GOS) | The Glasgow Outcome Scale evaluates the outcome as follow: 1 death, 2 vegetative state, 3 severe handicap, 4 moderate handicap, 5 good recovery. Favourable outcome: 4-5; unfavourable outcome: 1-3 | the GOS will be performed 6 months after the hospital admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital and ICU mortality | This outcome refers to the mortality during ICU stay and hospital stay | at the discharge from ICU, an expected average of 3 weeks; and at the discharge from hospital, an expected average of 6 weeks | 
| Length of ventilation | Days of ventilation, how long does it take to weaning from ventilation | during ICU stay, an expected average of 3 weeks | 
| Length of ICU and Hospital stay | How many days the patients whith cerebral infarction and without cerebral infarction have been in ICU, and how many days the patients were in hospital | at the discharge from ICU, an expected average of 3 weeks; and at the discharge from hospital, an expected average of 6 weeks |