The Safety of Simplified Tranexamic Acid Regimen

NCT07869537 | Recruiting Phase 4 DMC

• 1 other identifier: 2026-0904
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

Brief Summary

Trauma causes at least 5.8 million deaths worldwide annually, accounting for 1 in 10 of all global deaths. Uncontrolled bleeding within 24 hours after trauma is the leading cause of death in trauma patients, and about one-third of patients present with trauma-induced coagulopathy on admission. Fatal severe traumatic hemorrhage is the most common preventable factor contributing to death. Tranexamic acid (TXA), a synthetic lysine derivative, competitively inhibits plasminogen activation, preventing fibrin clot breakdown and thereby enhancing hemostasis and reducing blood loss. Randomized controlled trials such as CRASH-2 have confirmed that TXA significantly reduces mortality in patients with severe traumatic bleeding. TXA has therefore become a cornerstone of traumatic hemorrhage treatment, with current international guidelines recommending 1 g intravenous bolus (over \>10 minutes) plus 1 g intravenous maintenance infusion (over 8 hours). However, severe traumatic hemorrhage is typically managed in high-pressure, chaotic battlefield or emergency settings, where this complex, time-sensitive, multi-step divided regimen is difficult to fully execute in real-world practice. The omission rate of the second maintenance infusion is particularly high, reaching up to 67% during prehospital-to-hospital handover. Rowell et al. showed that even with a strict research protocol, completion of the planned 8-hour in-hospital maintenance infusion was only about 70%. Previous pharmacokinetic studies found that without the second maintenance dose, 21% of patients receiving an initial 1 g dose had already failed to achieve effective plasma concentrations at hospital admission (approximately 1.5 hours post-dose). Thus, the inherent difficulty of fully executing the divided regimen may prevent patients from receiving the full benefits of TXA. To address this, a simplified regimen of a single 2 g loading dose without maintenance infusion has been recommended in recent expert consensus statements, especially for prehospital or battlefield settings. However, these recommendations were mainly based on the 2020 Rowell et al. randomized controlled study, whose exploratory analysis suggested potential mortality reduction with the simplified regimen. That study enrolled patients with traumatic brain injury and had limited statistical power, so evidence on the efficacy and safety of the simplified regimen in patients with severe traumatic hemorrhage remains lacking. Based on the pharmacokinetic study by Grassin-Delyle et al., a single 2 g loading dose is hypothesized to maintain effective concentrations during the peak fibrinolytic period (within 3 hours post-injury), while the transient peak plasma concentration remains well below the toxicity threshold of 500 μg/mL. We therefore hypothesize that, in patients with severe traumatic hemorrhage, the simplified TXA regimen is non-inferior to the divided regimen in efficacy, including bleeding control. However, the primary limitation of a large randomized controlled trial to verify this hypothesis is that safety concerns regarding the simplified regimen due to higher transient plasma concentrations compared with the divided regimen have not been clearly resolved. Previous systematic reviews concluded that safety events such as thrombosis and seizures are dose-dependent, and that a total daily dose not exceeding 2 g is safe. Previous pharmacokinetic studies also suggest that the transient peak concentration of the simplified regimen should be well below the toxicity threshold. Although expert consensus has recommended the simplified regimen, suggesting it can be considered safe, studies directly comparing the two regimens are lacking, particularly regarding whether the simplified regimen increases safety risks when the total dose is identical. Before conducting a larger, more definitive efficacy trial, it is also important to evaluate recruitment rates, protocol adherence, accurate sample size estimation, and other potential barriers. For these reasons, we designed this pilot study, primarily to evaluate the safety of the simplified TXA regimen compared with the divided regimen in patients with traumatic hemorrhagic shock, and the feasibility of a subsequent randomized controlled trial.

Conditions

Trauma Coagulopathy; Hemorrhage

Keywords

trauma; hemorrhage; coagulopathy

Outcome Measures

Primary Outcomes (1)

• The incidence of thrombotic events

  Including deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, cerebral infarction and other thrombotic events

  in hospital

Secondary Outcomes (23)

• the incidence of deep venous thrombosis

  24 hour

• the incidence of deep venous thrombosis

  in hospital

• the incidence of pulmonary embolism

  in hospital

• the incidence of myocardial infarction

  in hospital

• the incidence of cerebrovascular embolism

  in hospital

Study Arms (2)

Simplified Tranexamic Acid Regimen

EXPERIMENTAL

Tranexamic Acid was administered intravenously within 3 hours after injury, with a loading dose of 2 g, and the infusion was completed after more than 20 minutes without a second dose.

Drug: Tranexamic Acid (TXA)

Divided-Dose Tranexamic Acid Regimen

ACTIVE COMPARATOR

Tranexamic Acid is administered intravenously within 3 hours after injury, with a loading dose of 1 g, and the infusion is completed after more than 10 minutes. The second dose of 1 g is maintained for 8 hours.

Drug: Tranexamic Acid (TXA)

Interventions

Tranexamic Acid (TXA) DRUG

Tranexamic Acid

Divided-Dose Tranexamic Acid Regimen; Simplified Tranexamic Acid Regimen

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Trauma patients
• Significant hemorrhage (systolic blood pressure \<90 mm Hg or heart rate \>110 beats per min, or both) or clinical assessment of risk of massive transfusion (massive transfusion was defined as administration of at least 3 PRBC within the hour of admission or at least 10 PRBC within the first 24 hours)
• who were within 3 h of injury
• To obtain informed consent (or comply with the requirements for emergency exemptions agree)

You may not qualify if:

• Known to be allergic to TXA
• Pregnancy
• Traumatic cardiac arrest occurring prior to or at the time of admission, or patients with a high risk of death within 3 hours of admission
• History of thrombotic disease (such as DVT and PE, MI, stroke)
• History of epilepsy
• Injury time is unknown or \> 3 hours
• have received TXA before admission.

Sponsors & Collaborators

• Second Affiliated Hospital, Zhejiang University, School of Medicine: lead
• Affiliated Hospital of Jiaxing University: collaborator
• The Third Affiliated Hospital of Wenzhou Medical University: collaborator
• The People's Hospital of Quzhou: collaborator
• Jinhua Central Hospital: collaborator

Study Sites (3)

the Second Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310009, China

RECRUITING

Jiaxing First Hospital

Jiaxin, Zhejiang, China

RECRUITING

Third Affiliated Hospital, Wenzhou Medical University

Wenzhou, Zhejiang, China

RECRUITING

MeSH Terms

Conditions

Hemorrhage; Wounds and Injuries; Hemostatic Disorders

Interventions

Tranexamic Acid

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• yongan xu, PhD

  Second Affiliated Hospital, Zhejiang University, School of Medicine

  STUDY CHAIR

Central Study Contacts

yongan xu

CONTACT

0571-87998893; xuyongan2000@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2026
• First Posted: October 9, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): April 30, 2027
• Last Updated: October 9, 2026

Record last verified: 2026-09

Locations

CN (3)