Clinical Randomisation of an Antifibrinolytic in Significant Head Injury (CRASH-3)

This study is currently recruiting participants.
Verified October 2012 by London School of Hygiene and Tropical Medicine
Sponsor:
Information provided by (Responsible Party):
London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier:
NCT01402882
First received: July 25, 2011
Last updated: October 2, 2012
Last verified: October 2012
  Purpose

The CRASH-3 trial will provide reliable evidence about the effect of tranexamic acid on mortality and disability in patients with traumatic brain injury. The effect of tranexamic acid on the risk of vascular occlusive events and seizures will also be assessed.


Condition Intervention Phase
Traumatic Brain Injury
Drug: Tranexamic Acid
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Tranexamic Acid for the Treatment of Significant Traumatic Brain Injury: an International Randomised, Double Blind Placebo Controlled Trial

Resource links provided by NLM:


Further study details as provided by London School of Hygiene and Tropical Medicine:

Primary Outcome Measures:
  • The primary outcome is death in hospital and cause of death will be described. [ Time Frame: within 28 days of injury ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • (a) Vascular occlusive events (myocardial infarction, stroke, pulmonary embolism, clinical evidence of deep vein thrombosis) [ Time Frame: Prior death, discharge or 28 days ] [ Designated as safety issue: Yes ]
  • (b) In hospital disability assessed using the Disability Rating Scale and Patient Orientated Outcome [ Time Frame: Prior death, discharge or 28 days ] [ Designated as safety issue: Yes ]
  • (c) Seizures [ Time Frame: Prior death, discharge or day 28 ] [ Designated as safety issue: Yes ]
  • (d) Neurosurgical intervention [ Time Frame: prior death, discharge or day 28 ] [ Designated as safety issue: Yes ]
  • (e) Days in intensive care [ Time Frame: prior death, discharge or day 28 ] [ Designated as safety issue: Yes ]
  • (f) Other adverse events [ Time Frame: prior death, discharge or day 28 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 10000
Study Start Date: September 2011
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tranexamic acid Drug: Tranexamic Acid
2 grams (1 gram over 10 minutes and 1 gram over 8 hours)
Placebo Comparator: Placebo Drug: Tranexamic Acid
2 grams (1 gram over 10 minutes and 1 gram over 8 hours)

Detailed Description:

BACKGROUND: Worldwide, over 10 million people are killed or hospitalised because of traumatic brain injury (TBI) each year. About 90% of deaths from TBI occur in low and middle income countries. TBI mostly affects young adults and many experiencing long lasting or permanent disability. The social and economic burden of TBI is considerable. Tranexamic acid (TXA) is commonly given to surgical patients to reduce bleeding and the need for blood transfusion. TXA has been shown to reduce the number of patients receiving a blood transfusion by about a third, reduces the volume of blood transfused by about one unit, and halves the need for further surgery to control bleeding in elective surgical patients. More recently, the CRASH-2 trial showed that the administration of TXA within 8 hours of injury significantly reduces deaths due to bleeding (RR=0.85, 95% CI 0.76-0.96; p=0.008), and all-cause mortality (RR=0.91, 95% CI 0.85-0.97; p=0.0035), with no apparent increase in vascular occlusive events. A meta-analysis of randomised controlled trials of TXA in TBI showed a significant reduction in haemorrhage growth (OR=0.61, 95%CI 0.41 to 0.91) and mortality (OR=0.59, 95%CI 0.35 to 0.99) with TXA. Although the results from these trials are promising, the estimates are imprecise and there are no data on the effect of TXA on disability.

AIM: The CRASH-3 trial will provide reliable evidence about the effect of tranexamic acid on mortality and disability in patients with TBI. The effect of TXA on the risk of vascular occlusive events and seizures will also be assessed.

PRIMARY OUTCOME: The primary outcome is death in hospital within 28 days of injury (cause of death will be described).

SECONDARY OUTCOMES:

  1. Vascular occlusive events (myocardial infarction, stroke, pulmonary embolism, clinical evidence of deep vein thrombosis)
  2. In hospital disability assessed using the Disability Rating Scale and Patient Orientated Outcome
  3. Seizures
  4. Neurosurgical intervention
  5. Days in intensive care Other adverse events will be described TRIAL DESIGN: A large, pragmatic, randomised, double blind, placebo controlled trial among 10,000 traumatic brain injury patients

DIAGNOSIS AND INCLUSION/EXCLUSION CRITERIA:

Adults with traumatic brain injury who

  • are within eight hours of injury
  • with any intracranial bleeding on CT scan or who have a GCS of 12 or less, and
  • have no significant extra-cranial haemorrhage The fundamental eligibility criterion is the responsible clinician's 'uncertainty' as to whether or not to use tranexamic acid in a particular patient with traumatic brain injury.

TEST PRODUCT, REFERENCE THERAPY, DOSE AND MODE OF ADMINISTRATION: A loading dose of tranexamic acid

(1 gram by intravenous injection) or placebo (sodium chloride 0.9%) will be given as soon as possible after randomisation. A maintenance dose of tranexamic acid (1 gram by intravenous injection) or placebo (sodium chloride 0.9%) will be given after the loading dose is finished.

SETTING: This trial will be coordinated from the London School of Hygiene & Tropical Medicine (University of London) and conducted worldwide in hospitals in low, middle and high income countries.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Adults with traumatic brain injury who

  • are within eight hours of injury
  • with any intracranial bleeding on CT scan or who have a GCS of 12 or less, and
  • have no significant extra-cranial haemorrhage The fundamental eligibility criterion is the responsible clinician's 'uncertainty' as to whether or not to use tranexamic acid in a particular patient with traumatic brain injury

Exclusion Criteria:

The fundamental eligibility criterion is the responsible clinician's 'uncertainty' as to whether or not to use tranexamic acid in a particular patient with traumatic brain injury

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01402882

Contacts
Contact: Haleema Shakur, BSc, MSc, RGN ++44(0)20 7958 8113 haleema.shakur@lshtm.ac.uk

Locations
Georgia
High Technology Medical Center, University Clinic Recruiting
Tblisi, Georgia
Contact: Tamar Gogichaishvili         
Sponsors and Collaborators
London School of Hygiene and Tropical Medicine
Investigators
Study Director: Haleema Shakur LSHTM
  More Information

Additional Information:
No publications provided by London School of Hygiene and Tropical Medicine

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier: NCT01402882     History of Changes
Other Study ID Numbers: ISRCTN15088122
Study First Received: July 25, 2011
Last Updated: October 2, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by London School of Hygiene and Tropical Medicine:
traumatic brain injury
tranexamic acid
antifibrinolytic
randomised
clinical trial

Additional relevant MeSH terms:
Brain Injuries
Wounds and Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Antifibrinolytic Agents
Tranexamic Acid
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 15, 2014