Pre-hospital Administration of Tranexamic Acid for Moderate and Severe Traumatic Brain Injury

Pre-hospital Administration of Tranexamic Acid for Adults With Moderate and Severe Traumatic Brain Injury: a Randomized, Double-blinded, Placebo-controlled Trial

This study is a prospective single-centre randomized trial to compare the effect of tranexamic acid versus placebo in the pre-hospital management of patients with moderate and severe traumatic brain injury.

Study Overview

• Status: Unknown
• Conditions: Brain Injuries, Traumatic
• Intervention / Treatment: Drug: Tranexamic Acid; Other: Sodium chloride

Detailed Description

Traumatic brain injury (TBI) remains a significant public health concern with poor outcome and one of the unmet needs in medical care. Tranexamic acid (TXA) has been shown to reduce blood loss after elective surgery and improve outcomes after traumatic injury due to bleeding without obvious adverse events. In the CRASH-2 Intracranial Bleeding Study, with the nested randomized trial design, the study showed that treatment with TXA within 8 hours of injury was associated with a reduction in haemorrhage growth [adjusted difference, -3.8 ml, 95% confidence interval (CI), -11.5 ml to 3.9 ml], fewer focal ischaemic lesions [adjusted odds ratio (OR) 0.54, 95% CI 0.20 to 1.46] and fewer death (adjusted OR 0.49, 95% CI 0.22 to 1.06) for patients with TBI (Glasgow coma score ≤ 14). The study also provided direction for future research of TXA in TBI, especially for the patients with moderate and severe TBI in whom an intracranial intracranial bleed (defined as the presence of parenchymal, subdural or epidural haemorrhage) is common.

Furtherly, results of the CRASH-2 trial stressed the importance of early adminstration with TXA for trauma patients, with the evidence showing that treatment of TXA within 1 hour post injury could significantly reduce the risk of death, while the benefit did not exist when TXA was administered more than 3 hours after injury. If the use of TXA could be incorporated into the pre-hospital management of TBI, the outcome of traumatically injured patients would be improved in an early stage. Thus, our study sets out to employ a randomized controlled study design, with a sample of 400 patients, to evaluate the efficacy and safety of early use of TXA in the pre-hospital management for moderate and severe TBI.

• Study Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Junfeng Feng, MD, PhD; Phone Number: 86-21-68383707; Email: fengjfmail@163.com
• Study Contact Backup: Name: Yanqing Ni, MD; Phone Number: 86-13601602411; Email: pd120xz@126.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200127
      • Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
      • Contact: Junfeng Feng, MD, PhD; Phone Number: 86-21-68383707; Email: fengjfmail@163.com
      • Contact: Yanqing Ni, MD; Phone Number: 86-21-68383707; Email: pd120xz@126.com
      • Principal Investigator: Guoyi Gao, MD, PhD
      • Principal Investigator: Yanqing Ni, MD
      • Sub-Investigator: Qing Mao, MD, PhD
      • Sub-Investigator: Junfeng Feng, MD, PhD
      • Sub-Investigator: Jijun Sheng, MD
      • Sub-Investigator: Hua Jiang, MD
      • Sub-Investigator: Junlai Gu, MD
      • Sub-Investigator: Jinghong Yang, MD
      • Sub-Investigator: Xianghui Lu, MD
      • Sub-Investigator: Xianfeng Qin, MD
      • Sub-Investigator: Zhiguo Wang, MD
      • Sub-Investigator: Jingde Xu, MD
      • Sub-Investigator: Hongguan Wang, MD
      • Sub-Investigator: Aiqun Cao, MD
      • Sub-Investigator: Cao Wang, MD
      • Sub-Investigator: Kaizhi Wang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• moderate to severe injuries(post-resuscitation scores Glasgow coma score of 4-12)
• age >= 18 year
• non-penetrating TBI in 2 hours onset

Exclusion Criteria:

• patients with coagulopathy
• pregnancy
• receiving any medication which affects haemostasis
• no consenting form

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tranexamic acid; Focused intervention	Drug: Tranexamic Acid; Tranexamic acid 1 gram in 100 ml saline, by intravenous drip over 10 minutes, once patient admitted to the trial on the spot of TBI; Other Names: Transamin
Placebo Comparator: Sodium chloride; Placebo control	Other: Sodium chloride; Sodium Chloride solution (0.9%) 1 ml (gram) in 100 ml saline, by intravenous drip over 10 minutes, once patient admitted to the trial on the spot of TBI; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glasgow Outcome Scale (GOS)	The GOS is five-category scale used for assessing the neurologic outcome after brain injury as follows: 1, death; 2, vegetative state - unable to interact with the environment; 3, severe disability - unable to live independently but able to follow commands; 4, moderate disability - capable of living independently but unable to return to work or school; and 5, good recovery - able to return to work or school. In our statistical analyses, the outcome will be further dichotomized in unfavorable (GOS 1-3) vs favorable (GOS 4-5); the proportion of unfavorable outcome will be compared between groups.	6 months post injury

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vascular occlusive events	Vascular occlusive events includes myocardial infarction, stroke, pulmonary embolism, clinical evidence of deep vein thrombosis.	6 months post injury
Death		6 months post injury
Length of intensive care unit stay		6 months post injury

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Collaborators: Shanghai Pudong Emergency Center
• Investigators: Principal Investigator: Guoyi Gao, MD, PhD, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University

Publications and helpful links

General Publications

• CRASH-2 trial collaborators, Shakur H, Roberts I, Bautista R, Caballero J, Coats T, Dewan Y, El-Sayed H, Gogichaishvili T, Gupta S, Herrera J, Hunt B, Iribhogbe P, Izurieta M, Khamis H, Komolafe E, Marrero MA, Mejia-Mantilla J, Miranda J, Morales C, Olaomi O, Olldashi F, Perel P, Peto R, Ramana PV, Ravi RR, Yutthakasemsunt S. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010 Jul 3;376(9734):23-32. doi: 10.1016/S0140-6736(10)60835-5. Epub 2010 Jun 14.

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): June 1, 2018

Study Registration Dates

• First Submitted: December 22, 2015
• First Submitted That Met QC Criteria: December 31, 2015
• First Posted (Estimate): January 1, 2016

Study Record Updates

• Last Update Posted (Estimate): January 1, 2016
• Last Update Submitted That Met QC Criteria: December 31, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Traumatic brain injury
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: TXA4TBI