Tranexamic Acid Mechanisms and Pharmacokinetics in Traumatic Injury

NCT02535949 | Completed Phase 2 Results DMC

• 1 other identifier: TAMPITI TRIAL
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

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.

Conditions

Hemorrhage; Shock; Wounds and Injuries

Outcome Measures

Primary Outcomes (1)

• Change in HLA-DR Expression on Monocytes 72 Hours After Drug or Placebo Administration in Patient Groups (0g TXA (Placebo); 2g TXA; 4g TXA)."

  Blood was drawn from patients at baseline (0 h, just before placebo or drug administration) and at 72 hours post placebo or drug administration. Leukocytes in these blood samples were stained with fluroescent antibodies specific for CD45, CD14, and HLA-DR, analyzed by flow cytometry, and the median fluorescen intensity (MFI) of HLA-DR signal was recorded for monocytes (CD45+CD14+). The fold change in HLA-DR expression from prior to placebo/drug administration to 72 h after placebo/drug administration ("0 h : 72 h") was calculated as HLA-DR MFI72hours ÷ HLA-DR CD14 MFI0hours. Non-paramteric one-way ANOVA (Kruskal-Wallis test) was performed between each treatment group at the given time pont, and the p-value reported.

  Samples Drawn through 72 hours after study initiation

Secondary Outcomes (13)

• Differences in Cytokine Profiles Between the Three Study Groups

  Samples Drawn through 72 hours after study initiation

• Differences in Leukocyte Function Parameters Between the Three Study Groups

  Samples Drawn through 72 hours after study initiation

• Total Transfusion Volume CL

  24 hours

• Determine the Incidence of Thromboembolic Events (DVT, MI, PE, Stroke) in All Three Study Groups.

  Hospital Discharge (average 10 days)

• Determine the Incidence of Seizures at 24 Hours in All Three Study Groups.

  24 hours following TXA

Study Arms (3)

Tranexamic Acid 2 Gram

EXPERIMENTAL

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

Drug: Tranexamic Acid

Tranexamic Acid 4 Gram

EXPERIMENTAL

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

Drug: Tranexamic Acid

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Tranexamic Acid 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.

Also known as: Cyklokapron

Tranexamic Acid 2 Gram; Tranexamic Acid 4 Gram

Placebo OTHER

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with traumatic injury that are ordered to receive at least 1 blood product and/or
• Patients admitted to the Emergency Department with a traumatic injury and require immediate transfer to the operating room to control the bleeding

You may not qualify if:

• Patients known to be \< 18 years of age
• Suspected Acute MI or stroke(thromboembolic and/or hemorrhagic) on admission
• Known inherited coagulation disorders
• 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
• Known history of seizures and/or seizure after injury/on admission related to this hospitalization
• Suspected or known pregnancy
• Known to be lactating
• Suspected or known prisoners
• Futile care
• Known current state of immunosuppression (i.e. on high dose steroids, chemotherapeutics, etc.)
• Unknown estimated time of injury 12). Patients wearing an "Opt Out" TAMPITI Study bracelet 13). Known presence of subarachnoid hemorrhage.
• ) Isolated injuries to hands and/or feet (distal) 15.) Administration of antifibrinolytics pre-hospital and/or during this ED admission prior to enrollment

Sponsors & Collaborators

• Washington University School of Medicine: lead
• United States Department of Defense: collaborator

Study Sites (1)

Barnes Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• 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.

  PMID: 33013880 DERIVED

MeSH Terms

Conditions

Hemorrhage; Shock; Wounds and Injuries

Interventions

Tranexamic Acid

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Results Point of Contact

• Title: Dr. Philip Spinella
• Organization: Washington University School of Medicine

pspinella@wustl.edu

314-286-0858

Study Officials

• Philip C Spinella, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2014
• First Posted: August 31, 2015
• Study Start: February 1, 2016
• Primary Completion: July 4, 2017
• Study Completion: July 7, 2017
• Last Updated: August 31, 2021
• Results First Posted: August 31, 2021

Record last verified: 2021-08

Locations

US (1)