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

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

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.

Study Overview

• Status: Completed
• Conditions: TBI (Traumatic Brain Injury); Stroke Acute
• Intervention / Treatment: Other: posttraumatic cerebral infarction

• Study Type: Observational
• Enrollment (Actual): 143

Contacts and Locations

Study Locations

• Italy
  • Brescia, Italy, 25123
    • Azienda Ospedaliera Spedali Civili di Brescia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

patients with moderate or severe brain injury, monitored with invasive intracranial pressure.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
TBI, no cerebral infarction; patients with moderate or severe brain injury that do not develop posttraumatic cerebral infarction
TBI, posttraumatic cerebral infarction; patients with moderate or severe brain injury that develops posttraumatic cerebral infarction	Other: posttraumatic cerebral infarction; the difference between groups refers to the developing of cerebral infarction after traumatic brain injury

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
• Collaborators: Azienda Ospedaliera Città della Salute e della Scienza di Torino; Azienda Ospedaliero, Universitaria Pisana; Fondazione Poliambulanza Istituto Ospedaliero; Università degli Studi di Brescia; A.O. Ospedale Papa Giovanni XXIII; Azienda Ospedaliera San Gerardo di Monza; Fondazione IRCCS Policlinico San Matteo di Pavia
• Investigators: Study Chair: Nicola Latronico, MD, University of Brescia and AO Spedali Civili di Brescia; Principal Investigator: Nazzareno Fagoni, MD, AO Spedali Civili di Brescia

Publications and helpful links

General Publications

• 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.
• Ghajar J. Traumatic brain injury. Lancet. 2000 Sep 9;356(9233):923-9. doi: 10.1016/S0140-6736(00)02689-1.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: April 16, 2015
• First Submitted That Met QC Criteria: April 27, 2015
• First Posted (Estimate): April 30, 2015

Study Record Updates

• Last Update Posted (Estimate): April 30, 2015
• Last Update Submitted That Met QC Criteria: April 27, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic
• Other Study ID Numbers: prot.1937/2009