Clinical trial NCT02430324: The Multicenter Italian INCEPT (INfarto CErebrale Post-Traumatico) Study
Official title: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: TBI (Traumatic Brain Injury)
Stroke Acute
Lead sponsor: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Sponsor class: OTHER
Collaborators: name: A.O.U. Città della Salute e della Scienza
name: Fondazione Poliambulanza Istituto Ospedaliero
name: A.O. Ospedale Papa Giovanni XXIII
name: Azienda Ospedaliera San Gerardo di Monza
name: Fondazione IRCCS Policlinico San Matteo di Pavia
name: Azienda Ospedaliero, Universitaria Pisana
name: Università degli Studi di Brescia
First posted: 2015-04-30
Enrollment: 143
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: patients with moderate or severe brain injury, monitored with invasive intracranial pressure.

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Oxford Handicap Scale (OHS)
timeFrame: patients will be evaluated at hospital discharge, an expected average of 3 weeks
measure: Glasgow Outcome Scale (GOS)
timeFrame: the GOS will be performed 6 months after the hospital admission
Secondary outcomes:
measure: Hospital and ICU mortality
timeFrame: at the discharge from ICU, an expected average of 3 weeks; and at the discharge from hospital, an expected average of 6 weeks
measure: Length of ventilation
timeFrame: during ICU stay, an expected average of 3 weeks
measure: Length of ICU and Hospital stay
timeFrame: at the discharge from ICU, an expected average of 3 weeks; and at the discharge from hospital, an expected average of 6 weeks
Other outcomes:
Locations:
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia
Study officials:
affiliation: University of Brescia and AO Spedali Civili di Brescia
name: Nicola Latronico, MD
role: STUDY_CHAIR
affiliation: AO Spedali Civili di Brescia
name: Nazzareno Fagoni, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ghajar J. Traumatic brain injury. Lancet. 2000 Sep 9;356(9233):923-9. doi: 10.1016/S0140-6736(00)02689-1.
citation: Marino R, Gasparotti R, Pinelli L, Manzoni D, Gritti P, Mardighian D, Latronico N. Posttraumatic cerebral infarction in patients with moderate or severe head trauma. Neurology. 2006 Oct 10;67(7):1165-71. doi: 10.1212/01.wnl.0000238081.35281.b5.
citation: Maas AI, Stocchetti N, Bullock R. Moderate and severe traumatic brain injury in adults. Lancet Neurol. 2008 Aug;7(8):728-41. doi: 10.1016/S1474-4422(08)70164-9.
citation: Mirvis SE, Wolf AL, Numaguchi Y, Corradino G, Joslyn JN. Posttraumatic cerebral infarction diagnosed by CT: prevalence, origin, and outcome. AJNR Am J Neuroradiol. 1990 Mar-Apr;11(2):355-60.
citation: Tawil I, Stein DM, Mirvis SE, Scalea TM. Posttraumatic cerebral infarction: incidence, outcome, and risk factors. J Trauma. 2008 Apr;64(4):849-53. doi: 10.1097/TA.0b013e318160c08a.
citation: Rosenfeld JV, Maas AI, Bragge P, Morganti-Kossmann MC, Manley GT, Gruen RL. Early management of severe traumatic brain injury. Lancet. 2012 Sep 22;380(9847):1088-98. doi: 10.1016/S0140-6736(12)60864-2.
citation: Lingsma HF, Roozenbeek B, Steyerberg EW, Murray GD, Maas AI. Early prognosis in traumatic brain injury: from prophecies to predictions. Lancet Neurol. 2010 May;9(5):543-54. doi: 10.1016/S1474-4422(10)70065-X.
citation: Stocchetti N, Maas AI. Traumatic intracranial hypertension. N Engl J Med. 2014 May 29;370(22):2121-30. doi: 10.1056/NEJMra1208708. No abstract available.
citation: Latronico N, Piva S, Fagoni N, Pinelli L, Frigerio M, Tintori D, Berardino M, Bottazzi A, Carnevale L, Casalicchio T, Castioni CA, Cavallo S, Cerasti D, Citerio G, Fontanella M, Galiberti S, Girardini A, Gritti P, Manara O, Maremmani P, Mazzani R, Natalini G, Patassini M, Perna ME, Pesaresi I, Radolovich DK, Saini M, Stefini R, Minelli C, Gasparotti R, Rasulo FA. Impact of a posttraumatic cerebral infarction on outcome in patients with TBI: the Italian multicenter cohort INCEPT study. Crit Care. 2020 Feb 3;24(1):33. doi: 10.1186/s13054-020-2746-5.