Effects of an Early Prehospital Administration of Tranexamic Acid on Hyperfibrinolysis in Multiple Trauma

Severe external and internal bleedings are common in multiple trauma patients. Uncontrollable blood loss is the cause for about one third of all trauma deaths. A number of blood clotting mechanisms are known to be triggered by major blood losses. These mechanisms shall secure the organisms from loosing even more blood. To avoid an overshooting clotting behavior, inhibiting mechanisms occur as well. An important inhibiting (or fibrinolytic) mechanism is the fibrinolysis that is based on the conversion of plasminogen to plasmin. In severe bleeding situations this mechanism tends to overshoot and therewith contributes to the severity of the bleeding. This phenomena is called hyperfibrinolysis and is found in approximately one third of all multiple trauma patients. Mortality rates are increased in these patients. Tranexamic acid is an antifibrinolytic drug that inhibits the conversion from plasminogen to plasmin and therefore is able to limit the effects hyperfibrinolysis. A large study showed positive influence of tranexamic acid on mortality rates and blood loss in severely injured patients, when it was administered in an early clinical setting. In this study we want to answer the question wether a hyperfibrinolysis can be seen in an early prehospital (on the scene) setting and how it is influenced by an early prehospital administration of tranexamic acid.

Study Overview

• Status: Completed
• Conditions: Mortality; Hyperfibrinolysis; Haemorrhage

Detailed Description

In patients suffering from multiple trauma the initially responding emergency physician on the scene will take a blood sample for thrombelastometry immediately after i.v. access is established. According to the initial trauma life support protocols a number of patients will receive a dose of tranexamic acid during the initial treatment on the scene or during transport to the hospital. A second blood sample will be taken after arrival in the resuscitation area of the hospital. Thrombelastometric measurements will be performed with both blood samples and the extent of hyperfibrinolysis in both samples will be compared. In a second step the outcome of the patients who received tranexamic acid on the scene will be compared to those who did not receive the drug before reaching hospital.

• Study Type: Observational
• Enrollment (Actual): 110

Contacts and Locations

Study Locations

• Germany
  • Lower Saxony
    • Goettingen, Lower Saxony, Germany, 37075
      • University Medical Center Göttingen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients will be recruited by emergency physicians on the scene by taking a blood sample for thrombelastometry.

Description

Inclusion Criteria:

• Multiple trauma ISS > 15
• Age > 18 years

Exclusion Criteria:

• No informed consent
• Inclusion to an interventional clinical trial
• Death of the patient on the scene or before the hospital was reached
• Delayed thrombelastometric measurement (> 4 hours)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Tranexamic acid; patients with multiple trauma who received tranexamic acid on the scene
Non tranexamic acid; patients with multiple trauma who did not receive tranexamic acid on the scene

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Initial state of hyperfibrinolysis	State of hyperfibrinolysis quantified by thromelastometry and PAP-Complex (Plasmin-Antiplasmin-Complex) from a blood sample taken a soon as possible on the scene	Minutes after arrival on the scene
State of hyperfibrinolysis on hospital admission	State of hyperfibrinolysis quantified by thrombelastometry and PAP-Complex from a blood sample taken as soon as possible after hospital arrival	minutes to hours after incident

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
transfusion of packed red blood cells	units of packed RBC units transfused within 48 hours after hospital admission	48 hours
substitution of coagulation products	number and type of coagulation products given within 48 hours after hospital admission	48 hours after hospital admission
length of stay intensive care unit (LOS ICU)	length of the first ICU stay	one year
length of hospital stay	length of stay in the acute care hospital (not rehabilitation facilities)	one year
mortality	dead within 90 days after hospital admission	90 days

Collaborators and Investigators

• Sponsor: University of Göttingen
• Collaborators: Tem International GmbH, München, Germany
• Investigators: Study Chair: Quintel Michael, Prof. Dr., University of Goettingen; Study Director: Roessler Markus, PD Dr., University of Goettingen

Publications and helpful links

General Publications

• CRASH-2 trial collaborators; Shakur H, Roberts I, Bautista R, Caballero J, Coats T, Dewan Y, El-Sayed H, Gogichaishvili T, Gupta S, Herrera J, Hunt B, Iribhogbe P, Izurieta M, Khamis H, Komolafe E, Marrero MA, Mejia-Mantilla J, Miranda J, Morales C, Olaomi O, Olldashi F, Perel P, Peto R, Ramana PV, Ravi RR, Yutthakasemsunt S. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010 Jul 3;376(9734):23-32. doi: 10.1016/S0140-6736(10)60835-5. Epub 2010 Jun 14.
• Schochl H, Frietsch T, Pavelka M, Jambor C. Hyperfibrinolysis after major trauma: differential diagnosis of lysis patterns and prognostic value of thrombelastometry. J Trauma. 2009 Jul;67(1):125-31. doi: 10.1097/TA.0b013e31818b2483.
• CRASH-2 collaborators; Roberts I, Shakur H, Afolabi A, Brohi K, Coats T, Dewan Y, Gando S, Guyatt G, Hunt BJ, Morales C, Perel P, Prieto-Merino D, Woolley T. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet. 2011 Mar 26;377(9771):1096-101, 1101.e1-2. doi: 10.1016/S0140-6736(11)60278-X.
• Kunze-Szikszay N, Krack LA, Wildenauer P, Wand S, Heyne T, Walliser K, Spering C, Bauer M, Quintel M, Roessler M. The pre-hospital administration of tranexamic acid to patients with multiple injuries and its effects on rotational thrombelastometry: a prospective observational study in pre-hospital emergency medicine. Scand J Trauma Resusc Emerg Med. 2016 Oct 10;24(1):122. doi: 10.1186/s13049-016-0314-4.

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (ACTUAL): September 1, 2015
• Study Completion (ACTUAL): October 1, 2015

Study Registration Dates

• First Submitted: September 5, 2013
• First Submitted That Met QC Criteria: September 5, 2013
• First Posted (ESTIMATE): September 10, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): December 2, 2015
• Last Update Submitted That Met QC Criteria: November 30, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Tranexamic acid; Polytrauma; Thrombelastometry; Multiple trauma; Hyperfibrinolysis
• Additional Relevant MeSH Terms: Pathologic Processes; Wounds and Injuries; Hemorrhage; Multiple Trauma
• Other Study ID Numbers: ZARI-NK-2013-02