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Trial registered on ANZCTR


Registration number
ACTRN12616001179426
Ethics application status
Approved
Date submitted
11/04/2016
Date registered
26/08/2016
Date last updated
26/08/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Coagulopathy in Severe, Isolated Traumatic Brain Injury: A Prevalence Study
Scientific title
Coagulopathy in Severe, Isolated Traumatic Brain Injury: A Prevalence Study
Secondary ID [1] 288976 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Traumatic Brain Injury 298368 0
Coagulopathy 298369 0
Condition category
Condition code
Injuries and Accidents 298473 298473 0 0
Other injuries and accidents

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Severe and isolated Traumatic Brain Injury patients, as defined by a GCS of less than or equal to 8/15 at any point in the first 12 (+- 3 hours) with radiological confirmation injury on CT brain. The time of injury will be taken as time zero. If this is unknown, the time of first medical contact (i.e Ambulance pick-up) or time of referral from secondary centre will be taken as time zero. Coagulation studies (TEG and INR, PTT, platelet count, serum urea) will be done at 12 hours (+- 3 hours), and 36 hours (+- 3 hours). If the 36 hour results are markedly abnormal, another final set of test will be done at 60 hours post injury. We will look for any evidence of coagulopathy as specified by the criteria below. We would like to note whether the same patients are determined to be coagulopathic according to standard TEG criteria and the laboratory defined abnormal values. If there is a difference in the prevalence of coagulopathy between standard testing (INR, PTT, platelet count) and TEG we will note any difference in sensitivities.
The criteria to determine the presence of a coagulopathy will be any one of the following:
1. Platelet count < 120 x 10^9 / ml
2. INR > 1.2
3. PTT > 37 seconds
4. TEG (any one of the following):
R time <4 minutes or > 8 minutes
K time > 4 minutes
a angle < 47 degrees or > 74 degrees
MA < 54 mm or > 72 mm
EPL> 15%
LY30 >8%
CI< -3 or > 3
The criteria for repeat sampling at 60 hours (+- 3 hours) are any one of the following: (+- 20 % outside of the normal values for coagulation testing and +- 10% outside the normal values for electrolytes)
1. Platelet count < 100 x 10^9 / ml or > 540 x 10^9 / ml
2. INR < 0.6 or > 1,4
3. PTT < 16 seconds or > 43 seconds
4. TEG
R time < 3 minutes or > 10 minutes
K time > 5 minutes
a angle < 38 degrees or > 88 degrees
CI < -4 or > 4
EPL > 20%
LY30 > 10%
5. Sodium < 122 mmol/l or > 159 mmol/l
Intervention code [1] 294463 0
Not applicable
Comparator / control treatment
We will observe whether there is any difference in the prevalence of coagulopathy between blunt and penetrating mechanisms of injury, as determined by TEG and standard coagulation testing (INR, PTT, platelet count). We will assess whether there is any difference in sensitivity of TEG and standard coagulation testing(INR, PTT, platelet count) in detecting the presence of a coagulopathy. We will not aim for equal numbers in each group, but will note any trend amongst the groups, if applicable.
Control group
Active

Outcomes
Primary outcome [1] 297962 0
Coagulopathy in isolated TBI patients. This will be
defined by any one of the following:
1. platelet count <120 x 109 /ml
2. INR > 1.2
3. PTT > 37 seconds
4. TEG (any one of the following criteria):
R time < 4 minutes or > 8 minutes
K time > 4 minutes
alpha angle < 47 degrees or > 74 degrees
MA < 54 mm or > 72 mm
EPL > 15%
LY30 > 8%
CI < -3 or > 3
Timepoint [1] 297962 0
12 hours(+- 3 hours), 36 hours(+- 3 hours), 60 hours(+- 3 hours) post injury.
Primary outcome [2] 299343 0
Sensitivity of TEG for diagnosis of coagulopathy, assessed by comparison with standard coagulopathy testing by serum INR, PTT and platelet count.
Timepoint [2] 299343 0
All timepoints are at time following injury (time of injury will be taken as time zero- details of how time zero is determined are specified elsewhere in the text):
1. 12 hours (+-3 hours)
2. 36 hours (+- 3 hours)
and if eligible according to the specified criteria
3. 60 hours (+- 3 hours)
Secondary outcome [1] 322770 0
To note any difference in the prevalences of coagulopathy (as defined by the above criteria) in blunt TBI and penetrating TBI
Timepoint [1] 322770 0
12 hours(+- 3 hours), 36 hours(+- 3 hours), 60 hours(+- 3 hours) post injury. Time zero will be the time of the injury or the time of first medical contact (i.e. time of ambulance pick up or time of referral from secondary hospital) if the time of injury is unknown.

Eligibility
Key inclusion criteria
Isolated head injury - Abbreviated Injury Score (AIS) >3 for head; AIS <3 for body
GCS less than or equal to 8/15
Age > 18 years
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Age <18 years
Significant other injuries, resulting in a body AIS score of >3
Head AIS < 3
Receipt of blood or blood products prior to admission to the study
Patients who have received tranexamic acid prior to admission to the study
Known coagulation abnormalities, including patients on therapeutic warfarin, enoxaparin, clopidogrel or aspirin

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
In a recent meta-analysis by Harhangi et al, a prevalence of 32.7% was noted. However, the studies included in this meta-analysis had widely varying prevalences, ranging from 10% to 97%. The criteria for coagulopathy also varied greatly between the studies included in the meta-analysis and may be partially responsible for the large discrepancies seen. It is therefore difficult to extrapolate or make assumptions based on their results.
Furthermore, there are no studies done on coagulation and isolated TBI in the South African population. Hence, a formal power calculation is not possible. We have elected to schedule blood sampling at times that are most likely to demonstrate coagulopathy and hence believe that 50 patients will be sufficient for the purposes of our study.

We will determine the prevalence of coagulopathy in traumatic brain injury (TBI). We will include both hypo- and hypercoagulopathy as defined by our criteria. We will note whether the prevalence of coagulopathy as determined by thromboelastography (TEG) differs from the prevalence of coagulopathy as determined by conventional laboratory testing as used in our institution. Lastly, we will note any differences between the prevalence of coagulopathy in blunt and penetrating mechanism of injury. We do not aim to have
equal numbers in each group for the purposes of this pilot study. Information collected in this manner may form the groundwork for future studies and may aide in sample size calculations for these future studies. We will observe which other patient parameters are linked with coagulopathies.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 7803 0
South Africa
State/province [1] 7803 0
Western Cape

Funding & Sponsors
Funding source category [1] 293333 0
University
Name [1] 293333 0
Department of Anaesthesia Research Committee
Address [1] 293333 0
Department of Anaesthesia, D23,
Groote Schuur Hospital
Main Road, Observatory,
Cape town 7935
Country [1] 293333 0
South Africa
Primary sponsor type
Individual
Name
Dr Anthony Reed
Address
Department of Anaesthesia, D23,
Groote Schuur Hospital
Main Road, Observatory,
Cape town 7935
Country
South Africa
Secondary sponsor category [1] 292152 0
None
Name [1] 292152 0
Address [1] 292152 0
Country [1] 292152 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294802 0
Human Research Ethics Committee
Ethics committee address [1] 294802 0
University of Cape Town
Faculty of Health Sciences
Groote Schuur Hospital
Old Main Building
E52 Room 24
Observatory, Cape Town 7935
Ethics committee country [1] 294802 0
South Africa
Date submitted for ethics approval [1] 294802 0
01/06/2015
Approval date [1] 294802 0
24/06/2015
Ethics approval number [1] 294802 0
380/2015

Summary
Brief summary
Coagulopathy is a well recognised sequela of severe TBI, and is frequently associated with prolonged intensive care unit stays and poor patient outcomes. Studies have shown that the mere presence of a coagulopathy was found to increase the likelihood of a poor outcome by a factor of 36 and the odds of mortality up to nine-fold. A meta-analysis done by Harhangi et al quotes the incidence of coagulopathy in TBI to be one in three patients, however varying reports document a incidence rate that ranges from between 10 to 100%. We would like to investigate the true incidence of coagulopathy following severe, isolated traumatic brain injury in the South African population and compare the results based on the mechanism of injury (i.e. blunt TBI vs penetrating TBI).

Thromboelastography (TEG) may be used as a tool for the global assessment of coagulation due to its unique ability to identify and assess all phases of haemostasis, thus allowing for the diagnosis of both hypo- and hyper-coagulable states. Native TEG has been extensively validated in trauma-induced coagulopathy as a point-of-care test, and has been used effectively to identify transfusion triggers in such patients.

Determining the prevalence hyper-coagulability as detected by TEG and comparing it with that detected with conventional laboratory values, may be beneficial in determining the need for anticoagulation in patients with TBI, as the risk for venous thromboembolism in these patients has been found to be three- to four-fold higher than trauma patients without TBI. If TEG is found to be more sensitive than conventional laboratory testing in detecting hyper-coagulability in these patients, it may become the standard of care in the future.

TEG associated hypo-coagulopathy has been shown to be a predictor of poor outcome (increased mortality, fewer ICU-free and hospital-free days) in patients with TBI. Furthermore, such hypo-coagulopathy has been linked with an increased need for neurosurgical intervention. The presence of coagulation abnormalities in patients undergoing emergent neurosurgery may critically affect the patients’ course, both in theatre and postoperatively. Prior knowledge of the presence of any coagulation abnormalities would lead to improved management in the peri-operative period, and hence contribute to the prevention of any secondary insults. This may, in turn, lead to an improved outcome, decreased length of stay and may help to minimise unnecessary transfusion of blood and blood products.

The purpose of this study is to detect the prevalence of coagulopathy in patients with severe, isolated traumatic brain injury in Cape Town, and to compare this to the published literature. Secondary outcomes will be to compare the prevalence of any changes between the group of patients with a closed versus penetrating TBI. We will be using standard coagulation screening (platelet count, INR and PTT) as well as a validated point of care coagulation screening test, the TEG.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 65102 0
Dr Anthony Reed
Address 65102 0
Department of Anaesthesia D23,
Groote Schuur Hospital
Main Road, Observatory
Cape Town 7935
Country 65102 0
South Africa
Phone 65102 0
+27214045001
Fax 65102 0
Email 65102 0
Anthony.Reed@uct.ac.za
Contact person for public queries
Name 65103 0
Dr Ruchi Lawrie
Address 65103 0
Department of Anaesthesia D23,
Groote Schuur Hospital
Main Road, Observatory
Cape Town 7935
Country 65103 0
South Africa
Phone 65103 0
+27214045001
Fax 65103 0
Email 65103 0
ruchi@lawrie.co.za
Contact person for scientific queries
Name 65104 0
Dr Anthony Reed
Address 65104 0
Department of Anaesthesia D23,
Groote Schuur Hospital
Main Road, Observatory
Cape Town 7935
Country 65104 0
South Africa
Phone 65104 0
+27214045001
Fax 65104 0
Email 65104 0
Anthony.Reed@uct.ac.za

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary