Tranexamic Acid Mechanisms and Pharmacokinetics in Traumatic Injury — TAMPITI  

Hemorrhage Clinical Trial

Official title: Tranexamic Acid Mechanisms and Pharmacokinetics in Traumatic Injury (TAMPITI TRIAL)

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Hemorrhage
• Shock
• Wounds and Injuries

• NCT number: NCT02535949
• Study type: Interventional
• Source: Washington University School of Medicine
• Status: Completed
• Phase: Phase 2
• Start date: February 2016
• Completion date: July 7, 2017