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| [ Print-friendly version ] |
| CRASH2 Trial, a large randomised placebo controlled trial among trauma patients with significant haemorrhage of the effects of an antifibrinolytic treatment on death and transfusion requirement |
| ISRCTN | ISRCTN86750102 |
| DOI | 10.1186/ISRCTN86750102 |
| ClinicalTrials.gov identifier | NCT00375258 |
| EudraCT number | |
| Public title | CRASH2 Trial, a large randomised placebo controlled trial among trauma patients with significant haemorrhage of the effects of an antifibrinolytic treatment on death and transfusion requirement |
| Scientific title | |
| Acronym | CRASH2 |
| Serial number at source | HTA 06/303/20; HTA 09/102/01; SLCTR/2007/008 |
| Study hypothesis |
Because the coagulation abnormalities that occur after injury are similar to those after surgery, it is possible that antifibrinolytic agents might also reduce blood loss, the need for transfusion and mortality following trauma. However, to date there has been only one small randomised controlled trial (70 randomised patients, drug versus placebo: 0 versus 3 deaths) of the effect of antifibrinolytic agents in major trauma. As a result, there is insufficient evidence to either support or refute a clinically important treatment effect. Systemic antifibrinolytic agents have been used in the management of eye injuries where there is some evidence that they reduce the rate of secondary haemorrhage.
CRASH2 aims to determine the effect of the early administration of the antifibrinolytic agent tranexamic acid (TXA) on death and transfusion requirement in adult trauma patients with ongoing significant haemorrhage, or who are considered to be at risk of significant haemorrhage. In addition, the effect on the risk of non-fatal vascular events (either haemorrhagic or occlusive) will be assessed. The initial stages of the trial was funded by the London School of Hygiene, the Bupa foundation and the Moulton Charitable Trust. In 2007, this trial obtained main funding from the NIHR Health Technology Assessment Programme, which will fund this trial from April 2007 to September 2010. More information on the CRASH2 trial can be found at: http://www.hta.ac.uk/1604 As of 16/06/2008, the CRASH2 trial will conduct sub-group analyses "CRASH-2 Intracranial Bleeding Study (IBS)" (Start date: October 2009) to study the effect of TXA in participants who also have traumatic brain injury (TBI). About 40% of participants out of 9,000 enrolled so far have TBI. Details of this sub-study can be found at: http://www.hta.ac.uk/2096 Hypothesis: Early administration of TXA can prevent the occurrence or increase of intracranial bleeding in patients with TBI and significant bleeding. Please note that, as of 21/08/2009, the anticipated start and end dates of this trial have been updated from 01/05/2005 and 30/04/2010 to 01/04/2007 and 30/09/2010, respectively. This trial completed follow-up on the 2nd March 2010, and the record was updated to reflect this on 09/07/2010. |
| Lay summary | Not provided at time of registration |
| Ethics approval | All trial centres will seek ethics approval before recruiting participants. As of 10/06/2008, over 275 approvals have been received. |
| Study design | Randomised placebo controlled trial |
| Countries of recruitment | International |
| Disease/condition/study domain | Trauma |
| Participants - inclusion criteria | All adult trauma patients who are considered to be at risk of significant haemorrhage and are within 8 hours of the injury, are eligible for trial entry if they appear to be at least 16 years old. There are no other pre-specified exclusion criteria, as the fundamental eligibility criterion is the responsible doctor's 'uncertainty' whether or not to use tranexamic acid (TXA) in a particular adult with traumatic haemorrhage. Patients for whom there is considered by the responsible doctor to be a clear indication for TXA should not be randomised. Likewise, any for whom there is considered to be a clear contraindication to TXA (such as, perhaps, those who have clinical evidence of a thrombotic disseminated intravascular coagulation) should not be randomised. All those for whom the responsible doctor is substantially uncertain as to whether or not to use an anti-fibrinolytic agent are eligible for randomisation, and as many such patients as possible should be considered for the trial. |
| Participants - exclusion criteria | The fundamental eligibility criterion is the responsible doctor's 'uncertainty' as to whether or not to use an antifibrinolytic agent in a particular adult with traumatic haemorrhage. Patients for whom the responsible doctor considers there is a clear indication for antifibrinolytic therapy should not be randomised. Likewise, patients for whom there is considered to be a clear contraindication to antifibrinolytic therapy (such as, perhaps, those who have clinical evidence of a thrombotic disseminated intravascular coagulation) should not be randomised. Where the responsible doctor is substantially uncertain as to whether or not to use an antifibrinolytic, all these patients are eligible for randomisation and should be considered for the trial. There are no other pre-specified exclusion criteria. |
| Anticipated start date | 01/04/2007 |
| Anticipated end date | 02/03/2010 |
| Status of trial | Completed |
| Patient information material | Patient information can be found at: http://www.crash2.lshtm.ac.uk |
| Target number of participants | 20,000 (Target number of participants for the sub-group analyses: up to 1,000) |
| Interventions |
Tranexamic acid 2 g intravenously over 8 hours versus placebo.
The list of all participating countries can be found at: http://www.crash2.lshtm.ac.uk Please note that as of 24/03/10 this trial has completed recruitment, analysis is ongoing. |
| Primary outcome measure(s) |
The primary outcome measure is death in hospital within four weeks of injury (causes of death will be classified).
An additional outcome measure for the sub-group analyses (added as of 18/06/2008): 1. Increase in volume of intracranial bleeding. A repeat CT scan will be carried out 24 - 48 hours after injury and compared to a clinical baseline CT scan. |
| Secondary outcome measure(s) |
Secondary outcome measures will be receipt of a blood transfusion, volume of blood transfused, surgical intervention and the occurrence of vascular events (haemorrhagic stroke, occlusive stroke, myocardial infarction, pulmonary embolism, clinically diagnosed deep vein thrombosis). Data will be recorded on a single sided outcome form which can be completed entirely from the hospital notes. There will be no additional tests.
Additional outcome measures for the sub-group analyses (added as of 18/06/2008): A repeat CT scan will be carried out 24 - 48 hours after injury and compared to a clinical baseline CT scan to assess the following: 1. Frequency of progressive haematomas 2. Frequency of delayed haematomas 3. New focal ischaemic lesions |
| Sources of funding |
1. NIHR Health Technology Assessment Programme - HTA (UK)
2. Bupa foundation (UK) 3. Moulton Charitable trust (UK) 4. London School of Hygiene and Tropical Medicine (UK) |
| Trial website | http://www.crash2.lshtm.ac.uk |
| Publications |
1. 2006 Letter to the Editor in http://www.ncbi.nlm.nih.gov/pubmed/16790038
2. 2006 initial progress results in http://www.ncbi.nlm.nih.gov/pubmed/17072431 3. 2010 effects of tranexamic acid results in http://www.ncbi.nlm.nih.gov/pubmed/20554319 4. 2011 early treatment results in http://www.ncbi.nlm.nih.gov/pubmed/21439633 5. 2011 tranexamic acid results in http://www.ncbi.nlm.nih.gov/pubmed/21702233 6. 2011 reduced environmental impact of trials in http://www.ncbi.nlm.nih.gov/pubmed/21291517 7. 2011 cost-effectiveness analysis results in http://www.ncbi.nlm.nih.gov/pubmed/21559279 8. 2011 tranexamic acid results in http://www.ncbi.nlm.nih.gov/pubmed/21724564 9. 2012 tranexamic acid results in http://www.ncbi.nlm.nih.gov/pubmed/22417901 10. 2012 tranexamic acid mortality results in http://www.ncbi.nlm.nih.gov/pubmed/22968527 11. 2013 results in www.ncbi.nlm.nih.gov/pubmed/23477634 |
| Contact name | Prof Ian Roberts |
| Address |
London School of Hygiene and Tropical Medicine
1st Floor, Wolfson Building Keppel Street |
| City/town | London |
| Zip/Postcode | WC1E 7HT |
| Country | United Kingdom |
| Tel | +44 (0)207 958 8128 |
| Fax | +44 (0)207 958 8111 |
| ian.roberts@lshtm.ac.uk | |
| Sponsor | London School of Hygiene and Tropical Medicine (UK) |
| Address | Keppel Street |
| City/town | London |
| Zip/Postcode | WC1E 7HT |
| Country | United Kingdom |
| haleema.shakur@lshtm.ac.uk | |
| Sponsor website: | http://www.lshtm.ac.uk/ |
| Date applied | 13/07/2004 |
| Last edited | 22/03/2013 |
| Date ISRCTN assigned | 10/09/2004 |
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| © 2013 ISRCTN unless otherwise stated. | |
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