Clinical trial NCT03616808: Thromboelastometry-identified Haemostatic Changes in Isolated Traumatic Brain Injury
Official title: The Influence of Thromboelastometry-identified Haemostatic Changes on Haemorrhagic Progression of Intracranial Injury and Clinical Outcome in Patients With Isolated Traumatic Brain Injury
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Coagulation Disorder
Brain Injuries, Traumatic
Bleeding
Keywords: Traumatic brain injury
Craniotomy
Goal-directed treatment
Thromboelastometry
Lead sponsor: Lithuanian University of Health Sciences
Sponsor class: OTHER
First posted: 2018-08-06
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A case-control study. Conventional management patients are considered as "controls" whereas goal-directed management patients will be considered "cases".
Primary purpose: TREATMENT

Brief summary: A prospective open-label case-control study will be performed aiming to assess the utility of thromboelastometry (ROTEM) for identification of hemostatic changes, goal-directed coagulation management, and prognosis of intracranial hemorrhagic injury progression as well as clinical outcome in patients with isolated traumatic brain injury. Patients undergoing craniotomy to treat traumatic brain injury will be enrolled. All patients will undergo standard perioperative coagulation analysis (APTT, PT, INR, fibrinogen levels, platelet count), whereas ROTEM-guided group will additionally be tested with ROTEM. "Cases" will be managed according to a ROTEM-based algorithm, and "Controls" will be treated as usual (based on clinical judging). Comparative analysis of acquired demographic, clinical and laboratory data will be performed. The investigators believe that ROTEM results could provide better insight into perioperative coagulation changes, be beneficial to patient blood management, and result in better outcome.

Detailed description: Aim of the study:

To assess the utility of thromboelastometry for identification of hemostatic changes, goal-directed coagulation management, and prognosis of intracranial hemorrhagic injury progression as well as clinical outcome in patients with isolated traumatic brain injury.

Objectives:

To evaluate perioperative prevalence and characteristics of thromboelastometry identified coagulopathy in neurosurgical patients with isolated traumatic brain injury; To assess the correlation between routine laboratory test results and thromboelastometric findings; To evaluate the influence of thromboelastometric findings and goal-directed coagulation management on the progression of intracranial hemorrhagic injury; To evaluate the utility of thromboelastometry for goal-directed coagulation management, and its possible influence on clinical outcome.

Study background:

Traumatic brain injury still accounts for a considerable proportion of preventable deaths worldwide. The prevalence of coagulation derangements among patients with traumatic brain injury (TBI) is high and approximates 30 % (1,2). The main hypothesis explaining the development of coagulopathy in the absence of massive bleeding is extensive release of tissue factor from the damaged brain tissue and subsequent over-activation of coagulation leading to consumption of coagulation substrates. The presence of coagulopathy in the setting of TBI is associated with high risk of intracranial hemorrhagic insult progression and death (3,4). Many authors investigating coagulopathy associated with traumatic brain injury have used routine coagulation tests, such as APTT, PT, INR, fibrinogen levels. However, those tests do not reflect the overall clot quality and reflect only separate parts of the coagulation process.

Craniotomy for traumatic brain injury is an urgent high-risk procedure presenting a serious challenge for the anesthesiology team. Significant, diffuse bleeding is not infrequent, and the spectrum of neurosurgical hemostatic options is limited. Moreover, even small amounts of intracranial blood may be life-threatening. Therefore the maintenance of optimal physiologic clotting capacity is crucial. Literature data investigating the use of ROTEM in TBI patients is still limited (5,6).

The investigators believe that thromboelastometry could provide novel insights into the dynamic coagulation changes of TBI patients. Moreover, it could serve as a clinical tool for targeted coagulation management in the perioperative period of patients undergoing craniotomies for intracranial traumatic hematomas, and prove beneficial for patient outcome.

Materials and methods:

A prospective open-label case-control study will be performed. Adult isolated traumatic brain injury patients undergoing craniotomy and will be enrolled. Required sample size was calculated based on the average number of craniotomies performed to treat traumatic brain injury during the past five years in a tertiary neurosurgical centre. The investigators plan to enroll 70 patients into the ROTEM-guided group (Cases), and 70 patients into the conventional therapy group (Controls). All patients will undergo standard coagulation analysis (APTT, PT, INR, fibrinogen levels, platelet count) preoperatively, and 3 days postoperatively, whereas ROTEM-guided group patients will additionally be tested with ROTEM (EXTEM, INTEM, FIBTEM, APTEM). Coagulation management decisions in the ROTEM-guided group will be made according to a ROTEM-based algorithm for goal-directed hemostatic therapy. Conventional therapy group will be treated as usual. Perioperative demographic, clinical and laboratory data of study patients will be registered. Early neurological state (on postoperative days 1,2,3,7, and until discharge) will be assessed according to the Glasgow coma scale. Late neurological outcome (6 and 12 months postoperatively) will be assessed according to Glasgow outcome scale. Comparative analysis of Case and Control groups will be performed. Perioperative prevalence and characteristics of coagulopathy in neurosurgical patients with isolated traumatic brain injury will be estimated. Correlation between routine laboratory test results and thromboelastometric findings will be assessed. The influence of thromboelastometric findings and goal-directed coagulation management on the progression of intracranial hemorrhagic injury will be assessed. The influence of goal-directed coagulation management on clinical outcome will be evaluated.

Anticipated scientific and clinical benefits:

The investigators believe that ROTEM results could provide better insight into perioperative coagulation changes, be beneficial to patient blood management, and result in better outcome.

Eligibility criteria: Inclusion Criteria:

* Isolated traumatic brain injury (within 48 hours) (AIS head \>= 3)
* Urgent craniotomy is necessary
* A written informed consent is acquired from the patient or his/her representative

Exclusion Criteria:

* Refusal / inability to acquire an informed consent
* Significant trauma to other body regions (AIS other regions \>= 3)
* Data on significant chronic hepatic or hematologic illness
* Use of oral anticoagulants or antiplatelet agents
* Pregnancy

Primary outcomes:
measure: Mortality
timeFrame: 30 days
measure: Early neurological state according to Glasgow coma scale
timeFrame: 30 days
Secondary outcomes:
measure: Coagulation abnormalities on conventional coagulation assays and ROTEM
timeFrame: 72 hours
measure: Progressive hemorrhagic injury
timeFrame: 30 days
measure: Clinical outcome according to Glasgow outcome score
timeFrame: Up to 1 year
Other outcomes:
measure: Correlation between conventional coagulation assays and ROTEM parameters
timeFrame: 72 hours
Locations:
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences
Study officials:
References:
citation: Wafaisade A, Lefering R, Tjardes T, Wutzler S, Simanski C, Paffrath T, Fischer P, Bouillon B, Maegele M; Trauma Registry of DGU. Acute coagulopathy in isolated blunt traumatic brain injury. Neurocrit Care. 2010 Apr;12(2):211-9. doi: 10.1007/s12028-009-9281-1.
citation: Harhangi BS, Kompanje EJ, Leebeek FW, Maas AI. Coagulation disorders after traumatic brain injury. Acta Neurochir (Wien). 2008 Feb;150(2):165-75; discussion 175. doi: 10.1007/s00701-007-1475-8. Epub 2008 Jan 2.
citation: Maegele M. Coagulopathy after traumatic brain injury: incidence, pathogenesis, and treatment options. Transfusion. 2013 Jan;53 Suppl 1:28S-37S. doi: 10.1111/trf.12033.
citation: de Oliveira Manoel AL, Neto AC, Veigas PV, Rizoli S. Traumatic brain injury associated coagulopathy. Neurocrit Care. 2015 Feb;22(1):34-44. doi: 10.1007/s12028-014-0026-4.
citation: Brazinova A, Majdan M, Leitgeb J, Trimmel H, Mauritz W; Austrian Working Group on Improvement of Early TBI Care. Factors that may improve outcomes of early traumatic brain injury care: prospective multicenter study in Austria. Scand J Trauma Resusc Emerg Med. 2015 Jul 16;23:53. doi: 10.1186/s13049-015-0133-z.
citation: Schochl H, Solomon C, Traintinger S, Nienaber U, Tacacs-Tolnai A, Windhofer C, Bahrami S, Voelckel W. Thromboelastometric (ROTEM) findings in patients suffering from isolated severe traumatic brain injury. J Neurotrauma. 2011 Oct;28(10):2033-41. doi: 10.1089/neu.2010.1744. Epub 2011 Sep 23.