Brain Injuries, TraumaticNCT04515420
The Influence of Noradrenaline on Coagulation and Fibrinolysis in Severe Isolated Brain Injury
An observational study of Brain Injuries, Traumatic and Coagulopathy, run by University Medical Centre Ljubljana.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Brain Injuries, Traumatic, Coagulopathy, Coagulation Defect; Acquired
- What is being tested?
- noradrenaline
- Type of treatment
- Injection or infusion
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2020to 1 Sep 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Adult, Older adult
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).
Who may be able to join
- patients with traumatic brain injury
- Glasgow Coma Scale ≤ 8
- Head Abbreviated Injury Scale (AIS) ≥ 3
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
No sites are listed yet.
About this study
Official title: The Influence of Noradrenaline Infusion on Coagulation and Fibrinolysis in Patients With Isolated Severe Brain Injury
Aim of the study
The investigators aim to establish:
Read more
- 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.
Read the detailed description
STUDY DESIGN AND METHODS The research shall be carried out at the Department of Anaesthetics and Surgical Intensive Care/Intensive Care Unit (ICU) at the University Medical Centre Ljubljana and will begin once it is approved by the Slovenian National Medical Ethics Committee. Patients will be included in the research once the informed consent form is signed by their relatives or their legal guardian.
Patients and the course of the study The research study will focus on 60 consecutive patients with severe traumatic brain injury (TBI) hospitalised at the emergency unit's ICU, 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). Both female and male patients, age 18 to 80, with Glasgow Coma Scale (GCS) ≤ 8 and Head Abbreviated Injury Scale (AIS) ≥ 3 shall be included in the study. Patients with any kind of extracranial injury, patients receiving anticoagulation or anti aggregation therapy, patients with a known neurological, haematological, malign or liver disease, patients with an infection and after a cardiac arrest, after craniotomy, patients that have received transfusion of concentrated erythrocytes (> 1 bag) and/or fresh frozen plasma, thrombocyte plasma, patients with a body temperature of < 35°C and pregnant women will all be excluded from the study, as will be those cases where it will be impossible to perform targeted tests in the expected time frame.
At the ICU, patients will receive treatment according to the guidelines for the treatment of severe traumatic brain injury. All patients will be sedated with midazolam, they will receive analgesia with fentanyl, and when required considering the level of ICP, will also receive a 2% propofol infusion. They will all be mechanically ventilated. A non-heparinized central venous catheter and an artery catheter will both be routinely inserted in all cases. Blood samples for the study will be taken from the internal jugular vein with a singular puncture.
Systemic blood pressure, heart rate, central body temperature, peripheral blood oxygen saturation (SpO2), ICP, cerebral perfusion pressure (CPP) and bispectral index (BIS) of the depth of anaesthesia will be monitored at all times. Pupillary response and depth of sedation using the Richmond Agitation-Sedation Scale (RASS) will be performed once per hour. Hydration will be estimated with stroke volume variation (SVV) one or twice per day. Patients whose CPP will not meet the desired value (70 mmHg) will receive systemic intravenous infusion of NA solution (0.16 mg/ml) in the dosage required to meet the target CPP. Another CT scan will be performed 12 to 24 hours after injury and after sudden deterioration in health condition, if necessary.
Blood samples will be taken daily from the artery catheter to determine the values of electrolytes, glucose, number of leukocytes and haemogram, number of thrombocytes all of which are routinely performed on a daily basis.
In the periods of 1-3, 6, 12 and 24 hours after injury, a member of the research staff will collect a blood sample from the patient with a severe TBI via an arterial catheter in order to determine: the level of endogenous NA or of total, endogenous and exogenous NA, if the patient will have received continuous NA infusion, the number of thrombocytes, prothrombin time/international normalized ration (PT/INR), activated partial thromboplastin time (aPTT), fibrinogen, antithrombin (AT), D-dimer, rotational thromboelastometry (ROTEM) test results, platelet function with aggregometry (Multiplate), lactate level, pH balance, gas analysis (PaO2, PaCO2), HCO3, base deficit and arterial blood oxygen saturation (SaO2). Venipuncture shall be performed on patients with severe TBI in the periods of 1-3, 6, 12 and 24 hours after injury by a member of the research staff to collect a blood sample from the jugular vein in order to determine: the level of endogenous NA or of total, endogenous and exogenous NA, if the patient will have received continuous NA infusion, number of thrombocytes, PT/INR, aPTT, fibrinogen, tissue factor (TF), AT, thrombin-antithrombin complex (TAT); D-dimer, tissue-plasminogen activator antigen (t-PAAg), plasminogen activator inhibitor-1 antigen (PAI-1Ag), plasminogen activator inhibitor-1 activity (PAI-1Act), plasmin-antiplasmin complex (PAP), plasminogen activity; protein C antigen (PCAg), syndecan-1 (SDC-1), rotational thromboelastometry (ROTEM) test results, platelet function with aggregometry (Multiplate). In patients who will require an infusion of NA within 1-3 hours after hemostasis tests have already been taken, the NA level will be determine again 30 minutes after the infusion set, and all mentioned hemostasis tests from the internal jugular vein and arterial catheter will be re-controlled. CT will be repeated 12 and 24 hours after the injury and if necessary in the case of a sudden worsening of the clinical condition.
Patients with severe TBI will be divided into two groups. Group A for patients that will need an infusion of NA solution to meet the desired CPP, and Group B for patients that will not receive NA infusion. 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. Absolute values of individual laboratory variables in different time intervals (1-3, 6, 12, 24 hours after injury) will be compared between Groups A and B, between sub-group A1 and B, A2 and B, and A3 and B; and between sub-groups A1, A2 and A3.
- Conditions
- Brain Injuries, Traumatic, Coagulopathy, Coagulation Defect; Acquired, Coagulation Defect; Bleeding, Fibrinolytic Hemorrhage, Acquired
- Being tested
- noradrenaline
- Keywords
- noradrenaline, thrombin generation, activation of coagulation, fibrinolysis, coagulation inhibition
- Medical subject headings
- Brain Injuries, Traumatic, Hemostatic Disorders, Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
noradrenalineDrug
noradrenaline infusion
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: noradrenaline | |
| Group B | Group B for patients that will not receive NA infusion. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 1 year
Secondary outcomes (3)
Change in basic haemostasis test between two groups
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. Change will be determinated by INR, activated partial trombin time in seconds, fibrinogen concentration in g/L and platelet count.
Measured: 1 year
Change of syndecan-1 plasma level
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. Change will be measured in ng/ml.
Measured: 1 year
Change of protein-C antigen
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. Concentration will be expressed in percentage.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2020
- Study start1 Sep 2020 (estimated)
- Primary completion1 Sep 2021 (estimated)
- Study completion1 Sep 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Brain Injuries, TraumaticStudies of the same condition, open and under way.
- More trials run by University Medical Centre LjubljanaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medical Centre Ljubljana
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Adela Stecher, University Medical Centre Ljubljana
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04515420
- Sponsor's protocol ID
- 123456
- Status last verified
- Aug 2020
- First submitted
- 7 Aug 2020
- Last updated
- 17 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Stein SC, Smith DH. Coagulopathy in traumatic brain injury. Neurocrit Care. 2004;1(4):479-88. doi: 10.1385/NCC:1:4:479.
PubMed 16174954Pathak 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.
PubMed 16010055Laroche 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.
PubMed 22307074Stein 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.
PubMed 15028145Cohen 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.
PubMed 18212647Rizoli 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.
PubMed 28228155Myburgh JA. Driving cerebral perfusion pressure with pressors: how, which, when? Crit Care Resusc. 2005 Sep;7(3):200-5.
PubMed 16545046Johansson 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.
PubMed 21772125von 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.
PubMed 30318393Tschuor 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.
PubMed 18564410
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Influence of Noradrenaline Infusion on Coagulation and Fibrinolysis in Patients With Isolated Severe Brain Injury
- ClinicalTrials.gov ID
- NCT04515420
- Acronym / sponsor ID
- 123456
- Conditions
- Brain Injuries, Traumatic, Coagulopathy, Coagulation Defect; Acquired, Coagulation Defect; Bleeding, Fibrinolytic Hemorrhage, Acquired
- Keywords
- noradrenaline, thrombin generation, activation of coagulation, fibrinolysis, coagulation inhibition
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University Medical Centre LjubljanaUniversity, hospital or other
- Study start
- 1 Sep 2020 (estimated)
- Primary completion
- 1 Sep 2021 (estimated)
- Study completion
- 1 Sep 2022 (estimated)
- First posted
- 17 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
STUDY DESIGN AND METHODS The research shall be carried out at the Department of Anaesthetics and Surgical Intensive Care/Intensive Care Unit (ICU) at the University Medical Centre Ljubljana and will begin once it is approved by the Slovenian National Medical Ethics Committee. Patients will be included in the research once the informed consent form is signed by their relatives or their legal guardian.
Patients and the course of the study The research study will focus on 60 consecutive patients with severe traumatic brain injury (TBI) hospitalised at the emergency unit's ICU, 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). Both female and male patients, age 18 to 80, with Glasgow Coma Scale (GCS) ≤ 8 and Head Abbreviated Injury Scale (AIS) ≥ 3 shall be included in the study. Patients with any kind of extracranial injury, patients receiving anticoagulation or anti aggregation therapy, patients with a known neurological, haematological, malign or liver disease, patients with an infection and after a cardiac arrest, after craniotomy, patients that have received transfusion of concentrated erythrocytes (> 1 bag) and/or fresh frozen plasma, thrombocyte plasma, patients with a body temperature of < 35°C and pregnant women will all be excluded from the study, as will be those cases where it will be impossible to perform targeted tests in the expected time frame.
At the ICU, patients will receive treatment according to the guidelines for the treatment of severe traumatic brain injury. All patients will be sedated with midazolam, they will receive analgesia with fentanyl, and when required considering the level of ICP, will also receive a 2% propofol infusion. They will all be mechanically ventilated. A non-heparinized central venous catheter and an artery catheter will both be routinely inserted in all cases. Blood samples for the study will be taken from the internal jugular vein with a singular puncture.
Systemic blood pressure, heart rate, central body temperature, peripheral blood oxygen saturation (SpO2), ICP, cerebral perfusion pressure (CPP) and bispectral index (BIS) of the depth of anaesthesia will be monitored at all times. Pupillary response and depth of sedation using the Richmond Agitation-Sedation Scale (RASS) will be performed once per hour. Hydration will be estimated with stroke volume variation (SVV) one or twice per day. Patients whose CPP will not meet the desired value (70 mmHg) will receive systemic intravenous infusion of NA solution (0.16 mg/ml) in the dosage required to meet the target CPP. Another CT scan will be performed 12 to 24 hours after injury and after sudden deterioration in health condition, if necessary.
Blood samples will be taken daily from the artery catheter to determine the values of electrolytes, glucose, number of leukocytes and haemogram, number of thrombocytes all of which are routinely performed on a daily basis.
In the periods of 1-3, 6, 12 and 24 hours after injury, a member of the research staff will collect a blood sample from the patient with a severe TBI via an arterial catheter in order to determine: the level of endogenous NA or of total, endogenous and exogenous NA, if the patient will have received continuous NA infusion, the number of thrombocytes, prothrombin time/international normalized ration (PT/INR), activated partial thromboplastin time (aPTT), fibrinogen, antithrombin (AT), D-dimer, rotational thromboelastometry (ROTEM) test results, platelet function with aggregometry (Multiplate), lactate level, pH balance, gas analysis (PaO2, PaCO2), HCO3, base deficit and arterial blood oxygen saturation (SaO2). Venipuncture shall be performed on patients with severe TBI in the periods of 1-3, 6, 12 and 24 hours after injury by a member of the research staff to collect a blood sample from the jugular vein in order to determine: the level of endogenous NA or of total, endogenous and exogenous NA, if the patient will have received continuous NA infusion, number of thrombocytes, PT/INR, aPTT, fibrinogen, tissue factor (TF), AT, thrombin-antithrombin complex (TAT); D-dimer, tissue-plasminogen activator antigen (t-PAAg), plasminogen activator inhibitor-1 antigen (PAI-1Ag), plasminogen activator inhibitor-1 activity (PAI-1Act), plasmin-antiplasmin complex (PAP), plasminogen activity; protein C antigen (PCAg), syndecan-1 (SDC-1), rotational thromboelastometry (ROTEM) test results, platelet function with aggregometry (Multiplate). In patients who will require an infusion of NA within 1-3 hours after hemostasis tests have already been taken, the NA level will be determine again 30 minutes after the infusion set, and all mentioned hemostasis tests from the internal jugular vein and arterial catheter will be re-controlled. CT will be repeated 12 and 24 hours after the injury and if necessary in the case of a sudden worsening of the clinical condition.
Patients with severe TBI will be divided into two groups. Group A for patients that will need an infusion of NA solution to meet the desired CPP, and Group B for patients that will not receive NA infusion. 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. Absolute values of individual laboratory variables in different time intervals (1-3, 6, 12, 24 hours after injury) will be compared between Groups A and B, between sub-group A1 and B, A2 and B, and A3 and B; and between sub-groups A1, A2 and A3.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A | – | Drug: noradrenalineGroup 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. |
| Group B | – | –Group B for patients that will not receive NA infusion. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Age groups
- Adult, Older adult
- 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).
Key inclusion criteria (3 listed)
- patients with traumatic brain injury
- Glasgow Coma Scale ≤ 8
- Head Abbreviated Injury Scale (AIS) ≥ 3
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| noradrenalinenoradrenaline infusion | Drug | Group A |
Primary outcome
Change of noradrenalin plasma levels between group A and group B
Time frame: 1 year
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.
Change of thrombin formation and fibrinolysis between group A and group B
Time frame: 1 year
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.
3 secondary outcomes
Change in basic haemostasis test between two groups
Time frame: 1 year
Change of syndecan-1 plasma level
Time frame: 1 year
Change of protein-C antigen
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2020.
- Results publication: PubMed 16174954Stein SC, Smith DH. Coagulopathy in traumatic brain injury. Neurocrit Care. 2004;1(4):479-88. doi: 10.1385/NCC:1:4:479.
- Results publication: PubMed 16010055Pathak 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.
- Results publication: PubMed 22307074Laroche 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.
- Results publication: PubMed 15028145Stein 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.
- Results publication: PubMed 18212647Cohen 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.
- Results publication: PubMed 28228155Rizoli 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.
- Results publication: PubMed 16545046Myburgh JA. Driving cerebral perfusion pressure with pressors: how, which, when? Crit Care Resusc. 2005 Sep;7(3):200-5.
- Results publication: PubMed 21772125Johansson 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.
- Results publication: PubMed 30318393von 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.
- Results publication: PubMed 18564410Tschuor 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
An observational study of Brain Injuries, Traumatic and Coagulopathy, run by University Medical Centre Ljubljana.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Adela Stecher, MSC (0038641360875, adela.stecher@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of noradrenalin plasma levels between group A and group B (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04515420, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2020.