ANZCTR - Registration

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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]

Nil

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Traumatic Brain Injury

Coagulopathy

Condition category

Condition code

Injuries and Accidents

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]

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]

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]

12 hours(+- 3 hours), 36 hours(+- 3 hours), 60 hours(+- 3 hours) post injury.

Primary outcome [2]

Sensitivity of TEG for diagnosis of coagulopathy, assessed by comparison with standard coagulopathy testing by serum INR, PTT and platelet count.

Timepoint [2]

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]

To note any difference in the prevalences of coagulopathy (as defined by the above criteria) in blunt TBI and penetrating TBI

Timepoint [1]

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

Sex

Both males and females

Can healthy volunteers participate?

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

16/10/2015

Date of last participant enrolment

Anticipated

Actual

5/06/2016

Date of last data collection

Anticipated

30/06/2016

Actual

8/06/2016

Sample size

Target

Accrual to date

Final

Recruitment outside Australia

Country [1]

South Africa

State/province [1]

Western Cape

Funding & Sponsors

Funding source category [1]

University

Name [1]

Department of Anaesthesia Research Committee

Address [1]

Department of Anaesthesia, D23,
Groote Schuur Hospital
Main Road, Observatory,
Cape town 7935

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Human Research Ethics Committee

Ethics committee address [1]

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]

South Africa

Date submitted for ethics approval [1]

01/06/2015

Approval date [1]

24/06/2015

Ethics approval number [1]

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

Dr Anthony Reed

Address

Department of Anaesthesia D23,
Groote Schuur Hospital
Main Road, Observatory
Cape Town 7935

Country

South Africa

Phone

+27214045001

Fax

Anthony.Reed@uct.ac.za

Contact person for public queries

Name

Ruchi Lawrie

Address

Department of Anaesthesia D23,
Groote Schuur Hospital
Main Road, Observatory
Cape Town 7935

Country

South Africa

Phone

+27214045001

Fax

ruchi@lawrie.co.za

Contact person for scientific queries

Name

Anthony Reed

Address

Department of Anaesthesia D23,
Groote Schuur Hospital
Main Road, Observatory
Cape Town 7935

Country

South Africa

Phone

+27214045001

Fax

Anthony.Reed@uct.ac.za

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

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No additional documents have been identified.

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