NCT04515420

Brief Summary

Aim of the study The investigators aim to establish:

  • Whether noradrenaline (NA) infusion has a significant effect on coagulation and fibrinolysis in patients with severe traumatic brain injury (TBI).
  • Whether disruption of haemostasis can be recorded with a computerized tomography (CT) scan.
  • Whether there is a significant difference between the values of haemostasis parameters in the internal jugular vein and the radialis artery. The hypotheses
  • In the early stage of treatment (1-3 hours), an increased formation of thrombin occurs in patients with severe isolated TBI that are treated with NA; consequently, platelet use increases in comparison with patients who don't need NA, as do coagulation factors and hyperfibrinolysis.
  • The concentration of NA correlates with thrombin formation and the correlation is stronger in higher doses of NA.
  • Thrombin formation will decrease more slowly in the group that will receive NA therapy in comparison to the group that will not receive NA therapy.

Trial Health

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
60

participants targeted

Target at P25-P50 for all trials

Timeline
Completed

Started Sep 2020

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 7, 2020

Completed
10 days until next milestone

First Posted

Study publicly available on registry

August 17, 2020

Completed
15 days until next milestone

Study Start

First participant enrolled

September 1, 2020

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2021

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2022

Completed
Last Updated

August 17, 2020

Status Verified

August 1, 2020

Enrollment Period

1 year

First QC Date

August 7, 2020

Last Update Submit

August 13, 2020

Conditions

Brain Injuries, TraumaticCoagulopathyCoagulation Defect; AcquiredCoagulation Defect; BleedingFibrinolytic Hemorrhage, Acquired

Keywords

noradrenalinethrombin generationactivation of coagulationfibrinolysiscoagulation inhibition

Outcome Measures

Primary Outcomes (2)

  • Change of noradrenalin plasma levels between group A and group B

    Blood sempling from the internal jugular vein will be done after 3, 6, 12, 24 hours after the injury. Blood will be centrifugated and plasma extracted. Plasma will be sent in the central hospital laboratory for plasma noradrenalin concentration measurement. Concentration will be expressed in pg/ml.

    1 year

  • Change of thrombin formation and fibrinolysis between group A and group B

    Blood sempling from the internal jugular vein will be done after 3, 6, 12, 24 hours after the injury. Blood will be centrifugated and plasma extracted. Plasma will be sent in the central hospital laboratory for measurement of tissue factor concentration in mcg/ml, antithrombin concentration in percents and thrombin-antitrombin complex concentration, as indirect indicator of trombin generation (concentration will be expressed in ng/ml). Fibrinolysis will be measured by the plasma levels of D-dimer in mcg/L, tissue plasminogen activator antigen in mcg/ml, plasminogen activator inhibitor-1 antigen in IU/ml, plasminogen activator inhibitor activity in mcg/ml, plasmin antiplasmin complex in mcg/ml and plasminogen concentration in mcg/ml.

    1 year

Secondary Outcomes (3)

  • Change in basic haemostasis test between two groups

    1 year

  • Change of syndecan-1 plasma level

    1 year

  • Change of protein-C antigen

    1 year

Study Arms (2)

Group A

Group A for patients that will need an infusion of NA solution to meet the desired CPP. Group A will be further divided into three sub-groups: A1 for patients that will receive NA in the dose of 0.06-0.12 μg/kg/min, A2 for patients that will receive a dose of 0.13-0.2 μg/kg/min, and A3 for patients that will receive a dose of NA \> 0.2 μg/kg/min.

Drug: noradrenaline

Group B

Group B for patients that will not receive NA infusion.

Interventions

noradrenalineDRUG

noradrenaline infusion

Group A

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

The research study will focus on 60 consecutive patients with severe traumatic brain injury (TBI) hospitalised at the emergency unit's ICU at the University Medical Center Ljubljana, who will be treated according to the Advanced Trauma Life Support guidelines, will undergo a computerized tomography (CT) scan of the head, and will have been implanted with an electrode for monitoring intracranial pressure (ICP).

You may qualify if:

  • patients with traumatic brain injury
  • Glasgow Coma Scale ≤ 8
  • Head Abbreviated Injury Scale (AIS) ≥ 3

You may not qualify if:

  • patients with any kind of extracranial injury
  • patients receiving anticoagulation or anti aggregation therapy
  • patients with a known neurological disorders
  • patients with haematological disorders
  • patients with malign diseases
  • patients with liver disease
  • patients with any infection
  • patients after cardiac arrest
  • patients after craniotomy
  • patients that have received transfusion of contentrated erythrocytes and/or fresh frozen plasma
  • patients that have received thrombocyte plasma
  • body temperature \<35°C
  • pregnant women

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (10)

  • Stein SC, Smith DH. Coagulopathy in traumatic brain injury. Neurocrit Care. 2004;1(4):479-88. doi: 10.1385/NCC:1:4:479.

    PMID: 16174954RESULT

  • Pathak A, Dutta S, Marwaha N, Singh D, Varma N, Mathuriya SN. Change in tissue thromboplastin content of brain following trauma. Neurol India. 2005 Jun;53(2):178-82. doi: 10.4103/0028-3886.16404.

    PMID: 16010055RESULT

  • Laroche M, Kutcher ME, Huang MC, Cohen MJ, Manley GT. Coagulopathy after traumatic brain injury. Neurosurgery. 2012 Jun;70(6):1334-45. doi: 10.1227/NEU.0b013e31824d179b.

    PMID: 22307074RESULT

  • Stein SC, Graham DI, Chen XH, Smith DH. Association between intravascular microthrombosis and cerebral ischemia in traumatic brain injury. Neurosurgery. 2004 Mar;54(3):687-91; discussion 691. doi: 10.1227/01.neu.0000108641.98845.88.

    PMID: 15028145RESULT

  • Cohen MJ, Brohi K, Ganter MT, Manley GT, Mackersie RC, Pittet JF. Early coagulopathy after traumatic brain injury: the role of hypoperfusion and the protein C pathway. J Trauma. 2007 Dec;63(6):1254-61; discussion 1261-2. doi: 10.1097/TA.0b013e318156ee4c.

    PMID: 18212647RESULT

  • Rizoli SB, Jaja BN, Di Battista AP, Rhind SG, Neto AC, da Costa L, Inaba K, da Luz LT, Nascimento B, Perez A, Baker AJ, de Oliveira Manoel AL. Catecholamines as outcome markers in isolated traumatic brain injury: the COMA-TBI study. Crit Care. 2017 Feb 23;21(1):37. doi: 10.1186/s13054-017-1620-6.

    PMID: 28228155RESULT

  • Myburgh JA. Driving cerebral perfusion pressure with pressors: how, which, when? Crit Care Resusc. 2005 Sep;7(3):200-5.

    PMID: 16545046RESULT

  • Johansson PI, Stensballe J, Rasmussen LS, Ostrowski SR. A high admission syndecan-1 level, a marker of endothelial glycocalyx degradation, is associated with inflammation, protein C depletion, fibrinolysis, and increased mortality in trauma patients. Ann Surg. 2011 Aug;254(2):194-200. doi: 10.1097/SLA.0b013e318226113d.

    PMID: 21772125RESULT

  • von Kanel R, Heimgartner N, Stutz M, Zuccarella-Hackl C, Hansel A, Ehlert U, Wirtz PH. Prothrombotic response to norepinephrine infusion, mimicking norepinephrine stress-reactivity effects, is partly mediated by alpha-adrenergic mechanisms. Psychoneuroendocrinology. 2019 Jul;105:44-50. doi: 10.1016/j.psyneuen.2018.09.018. Epub 2018 Sep 14.

    PMID: 30318393RESULT

  • Tschuor C, Asmis LM, Lenzlinger PM, Tanner M, Harter L, Keel M, Stocker R, Stover JF. In vitro norepinephrine significantly activates isolated platelets from healthy volunteers and critically ill patients following severe traumatic brain injury. Crit Care. 2008;12(3):R80. doi: 10.1186/cc6931. Epub 2008 Jun 18.

    PMID: 18564410RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

plasma

MeSH Terms

Conditions

Brain Injuries, TraumaticHemostatic DisordersHemorrhage

Interventions

Norepinephrine

Condition Hierarchy (Ancestors)

Brain InjuriesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesCraniocerebral TraumaTrauma, Nervous SystemWounds and InjuriesVascular DiseasesCardiovascular DiseasesHemorrhagic DisordersHematologic DiseasesHemic and Lymphatic DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

EthanolaminesAmino AlcoholsAlcoholsOrganic ChemicalsAminesBiogenic MonoaminesBiogenic AminesCatecholaminesCatecholsPhenolsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbons

Central Study Contacts

Adela Stecher, MSC

CONTACT

0038641360875adela.stecher@gmail.com

Ivan Kostadinov

CONTACT

0038641962566ivankostadinov@live.com

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

August 7, 2020

First Posted

August 17, 2020

Study Start

September 1, 2020

Primary Completion

September 1, 2021

Study Completion

September 1, 2022

Last Updated

August 17, 2020

Record last verified: 2020-08

Data Sharing

IPD Sharing
Will not share