Condition category
Injury, Occupational Diseases, Poisoning
Date applied
28/06/2011
Date assigned
19/07/2011
Last edited
29/06/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Worldwide, about 10 million people die or are hospitalised following a sudden head injury. Bleeding into the brain at the time of injury, which can continue many hours afterwards, is associated with increased rates of death and disability. It is important to find better ways of treating patients who bleed into the brain after a head injury. A drug called tranexamic acid has been shown to reduce death from bleeding after other types of traumatic injury. In addition, it is often used to reduce bleeding after major surgery such as heart operations. The CRASH-3 study is being done to see if tranexamic acid can improve outcomes for people after traumatic brain injury. The main outcome we will assess is the effect on the number of people who die from this injury. Other important outcomes will also be assessed such as its effect on disability and complications.

Who can participate?
Adults within eight hours of a head injury can take part in the CRASH-3 trial. Patients with significant bleeding outside of the head cannot take part. We plan to study 10,000 patients worldwide.

What does the study involve?
Patients with this problem will be admitted to hospital. Because this bleeding is an emergency situation, doctors will need to decide very quickly whether a patient is suitable for the trial or not (usually as soon as possible after the problem is identified). Brief information will be collected on an entry form to see if a patient is suitable. In this emergency situation it is difficult for patients to give written informed consent to take part. We will therefore ask the ethics committee for permission to put patients into the trial without written consent but where possible will get agreement from patients and relatives first, and we will explain to patients later what happened to them and how the information from the trial will be used. We have asked the opinions of members of the public about this and they agree that this is the only way we can do good research on life-threatening emergency problems. Everyone will get all the treatments that doctors usually give for this condition. In addition, they will get the trial treatment by an intravenous infusion (drip) for about 8 hours. Half of the patients will receive tranexamic acid and the other half a dummy medicine called a placebo. To make sure that the two groups are the same apart from tranexamic acid, we will decide who gets tranexamic acid and who gets placebo using a computer programme, a modern equivalent of the toss of a coin (this is called randomisation). We will collect some information on the progress of patients and whether they have any side effects for up to 28 days after they receive treatment.

What are the possible benefits and risks of participating?
We hope that tranexamic acid will help reduce the number of patients who die from this condition without increasing disability. The knowledge that we gain from this study will help other people with head injury in the future. Tranexamic acid is not a new drug. It has been used for years to reduce bleeding after operations and heavy menstruation and more recently to treat other types of serious injury. It works by stopping the breakdown of the blood clots which are needed to control bleeding. Studies have shown that it does not cause unwanted clotting and there are no serious side effects with short term use. However, patients will be monitored closely and doctors will report to the study organisers if there are any unexpected problems.

Where is the study run from?
The CRASH-3 trial is organised by the London School of Hygiene and Tropical Medicine (UK) and will involve hundreds of doctors and nurses worldwide.

When is the study starting and how long is it expected to run for?
We plan to enter patients into the trial from December 2011 until December 2016.

Who is funding the study?
The JP Moulton Charitable Trust, United Kingdom is funding the initial costs for this trial and the recruitment of up to 500 participants. Full funding is being sought from public funding organisations for the main trial.

Who is the main contact?
Ms Haleema Shakur
crash@lshtm.ac.uk

Trial website

http://crash3.lshtm.ac.uk/

Contact information

Type

Scientific

Primary contact

Prof Ian Roberts

ORCID ID

Contact details

Clinical Trials Unit
London School of Hygiene and Tropical Medicine
Keppel Street
London
WC1E 7HT
United Kingdom
-
crash@lshtm.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT01402882

Protocol/serial number

ISRCTN15088122

Study information

Scientific title

Tranexamic acid for the treatment of significant traumatic brain injury: an international randomised, double blind placebo controlled trial

Acronym

CRASH-3

Study hypothesis

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.

Protocol can be found at: https://ctu-web.lshtm.ac.uk/c3w/index.php/about/

Ethics approval

Not provided at time of registration

Study design

Large pragmatic randomised double-blind placebo-controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Patient information can be found at: https://ctu-web.lshtm.ac.uk/c3w/index.php/patient-information/

Condition

Traumatic Brain Injury

Intervention

1. Tranexamic acid versus placebo
2. Patients will be randomised to either tranexamic acid (loading dose 1 gram over 10 minutes then infusion of 1 gram over 8 hours) or matching placebo

Intervention type

Drug

Phase

Not Applicable

Drug names

Tranexamic acid

Primary outcome measures

Death in hospital within 28 days of injury (cause of death will be described)

Secondary outcome measures

1. Vascular occlusive events (myocardial infarction, stroke, pulmonary embolism, clinical evidence of deep vein thrombosis)
2. Disability assessed using the Disability Rating Scale and Patient Orientated Outcomes
3. Seizures
4. Neurosurgical intervention
5. Days in intensive care
6. Other adverse events will be described

Overall trial start date

01/09/2011

Overall trial end date

30/12/2016

Reason abandoned

Eligibility

Participant inclusion criteria

1. Adult
2. Traumatic brain injury
3. Within 8 hours of injury
4. Any intracranial bleeding on CT scan OR a GCS of 12 or less
5. No significant extra-cranial haemorrhage
6. Where the responsible clinician is substantially uncertain as to the appropriateness of antifibrinolytic agents in the patient

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

10,000 patients with head injury

Participant exclusion criteria

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

Recruitment start date

01/12/2011

Recruitment end date

30/12/2016

Locations

Countries of recruitment

Argentina, Azerbaijan, Cameroon, Canada, Colombia, Ecuador, El Salvador, Georgia, Greece, India, Indonesia, Italy, Jamaica, Kenya, Malaysia, Mexico, Nepal, Nigeria, Pakistan, Peru, Romania, Spain, Sri Lanka, Tanzania, Uganda, United Arab Emirates, United Kingdom, Zambia

Trial participating centre

London School of Hygiene and Tropical Medicine
London
WC1E 7HT
United Kingdom

Sponsor information

Organisation

London School of Hygiene and Tropical Medicine (UK)

Sponsor details

Keppel Street
London
WC1E 7HT
United Kingdom
+44 (0)20 7299 4684
crash@lshtm.ac.uk

Sponsor type

University/education

Website

http://www.lshtm.ac.uk/

Funders

Funder type

University/education

Funder name

London School of Hygiene and Tropical Medicine (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

J P Moulton Charitable Foundation (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2012 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/22721545

Publication citations

  1. Protocol

    Dewan Y, Komolafe EO, Mejía-Mantilla JH, Perel P, Roberts I, Shakur H, , 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, 13, 87, doi: 10.1186/1745-6215-13-87.

Additional files

Editorial Notes