Tranexamic Acid Mechanisms and Pharmacokinetics in Traumatic Injury

NCT ID: NCT02535949

Last Updated: 2021-08-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2017-07-07

Brief Summary

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.

Detailed 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.

Conditions

Hemorrhage; Shock; Wounds and Injuries

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Tranexamic Acid 2 Gram

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

Group Type: EXPERIMENTAL

Tranexamic Acid

Intervention Type: DRUG

Tranexamic acid is a man-made form of an amino acid (protein) called lysine. Tranexamic acid prevents enzymes in the body from breaking down blood clots.

Tranexamic Acid 4 Gram

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

Group Type: EXPERIMENTAL

Tranexamic Acid

Intervention Type: DRUG

Tranexamic acid is a man-made form of an amino acid (protein) called lysine. Tranexamic acid prevents enzymes in the body from breaking down blood clots.

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

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

Interventions

Tranexamic Acid

Tranexamic acid is a man-made form of an amino acid (protein) called lysine. Tranexamic acid prevents enzymes in the body from breaking down blood clots.

Intervention Type: DRUG

Placebo

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

Intervention Type: OTHER

Other Intervention Names

Cyklokapron

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

United States Department of Defense

FED

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philip C Spinella, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Barnes Jewish Hospital

St Louis, Missouri, United States

Countries

United States

References

Spinella PC, Thomas KA, Turnbull IR, Fuchs A, Bochicchio K, Schuerer D, Reese S, Coleoglou Centeno AA, Horn CB, Baty J, Shea SM, Meledeo MA, Pusateri AE, Levy JH, Cap AP, Bochicchio GV; TAMPITI Investigators. The Immunologic Effect of Early Intravenous Two and Four Gram Bolus Dosing of Tranexamic Acid Compared to Placebo in Patients With Severe Traumatic Bleeding (TAMPITI): A Randomized, Double-Blind, Placebo-Controlled, Single-Center Trial. Front Immunol. 2020 Sep 8;11:2085. doi: 10.3389/fimmu.2020.02085. eCollection 2020.

Reference Type: DERIVED

PMID: 33013880 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

TAMPITI TRIAL

Identifier Type: -

Identifier Source: org_study_id