Tranexamic Acid Mechanisms and Pharmacokinetics in Traumatic Injury (TAMPITI)

The Washington University

Status and phase: Completed; Phase 2

Conditions: Shock; Hemorrhage; Wounds and Injuries

Treatments: Other: Placebo; Drug: Tranexamic Acid

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT02535949

TAMPITI TRIAL

Details and patient eligibility

About

The purpose of this study is to evaluate the effects of TXA on the immune system, its pharmacokinetics, as well as safety and efficacy in severely injured trauma patients.

Full description

Trauma is the leading cause of death in persons younger than 40 years. Hemorrhage is the etiology in 30% of these deaths, and remains the leading cause of potentially preventable mortality (66-80%) on the battlefield. Death secondary to hemorrhagic shock occurs from both surgical bleeding and coagulopathy. Due to the knowledge of increased fibrinolysis promoting a hypocoagulable state in severe trauma, trials have been performed to determine if antifibrinolytics such as tranexamic acid (TXA) could reduce morbidity and mortality by reducing death from hemorrhage. TXA is an antifibrinolytic that inhibits both plasminogen activation and plasmin activity, thus preventing clot break-down rather than promoting new clot formation. Despite the extensive use of TXA in many surgical populations and an increasing use in severe trauma patients, TXA does not have an FDA approved indication for patients with traumatic injuries. The effect of TXA on immune function has not been thoroughly examined, especially in patients with severe traumatic injury. The study of the effects of TXA use on endothelial activation and injury is also important due to the inter-relationship between coagulation and endothelial function. Endothelial injury secondary to local hypoperfusion causes acute traumatic coagulopathy with fibrinolysis. Therefore a thorough and comprehensive evaluation of the effects of TXA on immune, coagulation, and endothelial parameters is important to allow for a better understanding of the mechanisms of action of this agent.

This is a randomized placebo controlled trial to obtain mechanism of action data, pharmacokinetic information, and efficacy and safety data for the use of TXA in severely injured trauma patients. Participants will be randomized into 1 of 3 treatment arms (1:1:1): TXA 2 gram IV bolus, TXA 4 gram IV bolus, or placebo. The study period is from time of enrollment to hospital discharge or transfer. The study intervention will occur only once upon enrollment in the trial. Participants will receive study drug within two hours from their initial injury. Blood samples will be drawn at multiple time points for immune parameters, Pharmacodynamics, and repository samples.

Immune parameter samples will be drawn at at approximately 0, 6, 24 and 72 hours after study drug/placebo administration.

Pharmacokinetic and pharmacodynamic samples will be drawn according to two schedules. Even number sampling times, blood will be drawn at the approximate time points: 0, 20 min, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, and 12 hr. A patient sampled on odd number sampling times will have samples drawn at the approximate time points: 0, 10 min, 40 min, 1.5 hr, 3 hr, 6 hr, 10 hr and 24 hr.

Repository samples will be drawn at approximate time points: 0, 1, 6, 24, and 72 hours.

Enrollment: 150 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients with traumatic injury that are ordered to receive at least 1 blood product and/or
2. Patients admitted to the Emergency Department with a traumatic injury and require immediate transfer to the operating room to control the bleeding
3. Able to receive the study drug within 2 hours from estimated time of injury **Please note that in circumstances where the patient initially met inclusion/exclusion criteria (i.e. received blood products in the ED before a full evaluation of their injuries is complete) but is later found to only have a soft tissue involved injury or does not have a traumatic bleeding source), the Investigator may determine that the patient should not be randomized into the trial and the patient should be considered a screen failure

Exclusion criteria

1. Patients known to be < 18 years of age

2. Suspected Acute MI or stroke(thromboembolic and/or hemorrhagic) on admission

3. Known inherited coagulation disorders

4. Known history of thromboembolic events (DVT, PE, MI, Stroke)

   • Please note that past medical history of hemorrhagic stroke is permitted, but not current admission with hemorrhagic stroke

5. Known history of seizures and/or seizure after injury/on admission related to this hospitalization

6. Suspected or known pregnancy

7. Known to be lactating

8. Suspected or known prisoners

9. Futile care

10. Known current state of immunosuppression (i.e. on high dose steroids, chemotherapeutics, etc.)

11. Unknown estimated time of injury 12). Patients wearing an "Opt Out" TAMPITI Study bracelet 13). Known presence of subarachnoid hemorrhage.

14.) Isolated injuries to hands and/or feet (distal) 15.) Administration of antifibrinolytics pre-hospital and/or during this ED admission prior to enrollment

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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150 participants in 3 patient groups, including a placebo group

Tranexamic Acid 2 Gram

Experimental group

Description:

One time dose IV TXA 2 Grams given over 10 minutes within 2 hours of initial injury

Treatment:

Drug: Tranexamic Acid

Tranexamic Acid 4 Gram

Experimental group

Description:

One time dose IV TXA 4 Grams given over 10 minutes within 2 hours of initial injury

Treatment:

Drug: Tranexamic Acid

Placebo

Placebo Comparator group

Description:

Matching Volume Normal Saline Placebo given IV over 10 minutes within 2 hours of initial injury

Treatment:

Other: Placebo