Clinical Randomisation of an Antifibrinolytic in Significant Head Injury

NCT01402882 | Completed Phase 3 DMC

• 1 other identifier: ISRCTN15088122
• Study Type: interventional
• Target: 12,737
• Locations: 1 country
• Sites: 1

Brief Summary

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. Additionally, a nested study will be conducted in a subset of CRASH-3 trial participants. This nested study (CRASH-3 Intracranial Bleeding Sub-Study \[CRASH-3 IBS\]) will examine the effect of tranexamic acid on intracranial haemorrhage and cerebral ischaemia using CT Scans in approximately 1,000 patients randomised into the CRASH-3 trial.

Conditions

Traumatic Brain Injury

Keywords

traumatic brain injury; tranexamic acid; antifibrinolytic; randomised; clinical trial

Outcome Measures

Primary Outcomes (1)

• The primary outcome is death in hospital in patients recruited within 3 hours and cause of death will be described.

  within 28 days of injury

Secondary Outcomes (6)

• (a) Vascular occlusive events (myocardial infarction, stroke, pulmonary embolism, clinical evidence of deep vein thrombosis)

  Prior death, discharge or 28 days

• (b) In hospital disability assessed using the Disability Rating Scale and Patient Orientated Outcome

  Prior death, discharge or 28 days

• (c) Seizures

  Prior death, discharge or day 28

• (d) Neurosurgical intervention

  prior death, discharge or day 28

• (e) Days in intensive care

  prior death, discharge or day 28

Other Outcomes (5)

• CRASH-3 IBS: Primary outcome - the total volume of intracranial haemorrhage

  1) CT scan done before receipt of trial treatment; (2) CT scan done after receipt of trial treatment (up to 28 days after randomisation)

• Frequency of progressive haemorrhage: number of patients with a post-randomisation CT scan with total haemorrhage volume of more than 25% of the volume on the pre-randomisation scan

  1) CT scan done before receipt of trial treatment; (2) CT scan done after receipt of trial treatment (up to 28 days after randomisation)

• Frequency of delayed haemorrhage:

  1) CT scan done before receipt of trial treatment; (2) CT scan done after receipt of trial treatment (up to 28 days after randomisation)

Study Arms (2)

Tranexamic acid

EXPERIMENTAL

Drug: Tranexamic Acid

Placebo

PLACEBO COMPARATOR

(Sodium Chloride 0.9%)

Drug: Tranexamic Acid

Interventions

Tranexamic Acid DRUG

2 grams (1 gram over 10 minutes and 1 gram over 8 hours)

Placebo; Tranexamic acid

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults with traumatic brain injury who
• are within eight hours of injury (limited to within 3 hours from September, 2016)
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead

Study Sites (1)

High Technology Medical Center, University Clinic

Tbilisi, Georgia

Location

Related Publications (8)

• Mansukhani R, Belli A, Brenner A, Chaudhri R, Frimley L, Faizah Jamaluddin S, Jooma R, Shakur-Still H, Shokunbi T, Roberts I. Effect of early tranexamic acid treatment on fatigue in patients with mild traumatic brain injury: data from the CRASH-3 clinical trial. Wellcome Open Res. 2024 Oct 28;6:346. doi: 10.12688/wellcomeopenres.17421.3. eCollection 2021.

  PMID: 39502454 DERIVED

• Roberts I, Shakur-Still H, Aeron-Thomas A, Beaumont D, Belli A, Brenner A, Cargill M, Chaudhri R, Douglas N, Frimley L, Gilliam C, Geer A, Jamal Z, Jooma R, Mansukhani R, Miners A, Pott J, Prowse D, Shokunbi T, Williams J. Tranexamic acid to reduce head injury death in people with traumatic brain injury: the CRASH-3 international RCT. Health Technol Assess. 2021 Apr;25(26):1-76. doi: 10.3310/hta25260.

  PMID: 33928903 DERIVED

• Brenner A, Belli A, Chaudhri R, Coats T, Frimley L, Jamaluddin SF, Jooma R, Mansukhani R, Sandercock P, Shakur-Still H, Shokunbi T, Roberts I; CRASH-3 trial collaborators. Understanding the neuroprotective effect of tranexamic acid: an exploratory analysis of the CRASH-3 randomised trial. Crit Care. 2020 Nov 11;24(1):560. doi: 10.1186/s13054-020-03243-4.

  PMID: 33172504 DERIVED

• Mansukhani R, Frimley L, Shakur-Still H, Sharples L, Roberts I. Accuracy of time to treatment estimates in the CRASH-3 clinical trial: impact on the trial results. Trials. 2020 Jul 25;21(1):681. doi: 10.1186/s13063-020-04623-5.

  PMID: 32711551 DERIVED

• CRASH-3 trial collaborators. Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial. Lancet. 2019 Nov 9;394(10210):1713-1723. doi: 10.1016/S0140-6736(19)32233-0. Epub 2019 Oct 14.

  PMID: 31623894 DERIVED

• Roberts I, Belli A, Brenner A, Chaudhri R, Fawole B, Harris T, Jooma R, Mahmood A, Shokunbi T, Shakur H; CRASH-3 trial collaborators. Tranexamic acid for significant traumatic brain injury (The CRASH-3 trial): Statistical analysis plan for an international, randomised, double-blind, placebo-controlled trial. Wellcome Open Res. 2018 Sep 26;3:86. doi: 10.12688/wellcomeopenres.14700.2. eCollection 2018.

  PMID: 30175246 DERIVED

• Mahmood A, Roberts I, Shakur H. A nested mechanistic sub-study into the effect of tranexamic acid versus placebo on intracranial haemorrhage and cerebral ischaemia in isolated traumatic brain injury: study protocol for a randomised controlled trial (CRASH-3 Trial Intracranial Bleeding Mechanistic Sub-Study [CRASH-3 IBMS]). Trials. 2017 Jul 17;18(1):330. doi: 10.1186/s13063-017-2073-6.

  PMID: 28716153 DERIVED

• Dewan Y, Komolafe EO, Mejia-Mantilla JH, Perel P, Roberts I, Shakur H; CRASH-3 Collaborators. CRASH-3 - tranexamic acid for the treatment of significant traumatic brain injury: study protocol for an international randomized, double-blind, placebo-controlled trial. Trials. 2012 Jun 21;13:87. doi: 10.1186/1745-6215-13-87.

  PMID: 22721545 DERIVED

Related Links

• Trial website

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

Tranexamic Acid

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

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

Study Officials

• Haleema Shakur

  London School of Hygiene and Tropical Medicine

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2011
• First Posted: July 26, 2011
• Study Start: July 1, 2012
• Primary Completion: October 1, 2019
• Study Completion: October 1, 2019
• Last Updated: February 17, 2020

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will share

Locations

GE (1)