Effect of tranexamic acid in traumatic brain injury: a nested randomised, placebo controlled trial (CRASH-2 Intracranial Bleeding Study)BMJ 2011; 343 doi: https://doi.org/10.1136/bmj.d3795 (Published 01 July 2011) Cite this as: BMJ 2011;343:d3795
- CRASH-2 Collaborators (Intracranial Bleeding Study)
- Correspondence to: Clinical Trials Unit, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK
- Accepted 10 May 2011
Objective To assess the effect of tranexamic acid (which reduces bleeding in surgical patients and reduces mortality due to bleeding in trauma patients) on intracranial haemorrhage in patients with traumatic brain injury.
Methods A nested, randomised, placebo controlled trial. All investigators were masked to treatment allocation. All analyses were by intention to treat.
Patients 270 adult trauma patients with, or at risk of, significant extracranial bleeding within 8 hours of injury, who also had traumatic brain injury.
Interventions Patients randomly allocated to tranexamic acid (loading dose 1 g over 10 minutes, then infusion of 1 g over 8 hours) or matching placebo.
Main outcome measures Intracranial haemorrhage growth (measured by computed tomography) between hospital admission and then 24–48 hours later, with adjustment for Glasgow coma score, age, time from injury to the scans, and initial haemorrhage volume.
Results Of the 133 patients allocated to tranexamic acid and 137 allocated to placebo, 123 (92%) and 126 (92%) respectively provided information on the primary outcome. All patients provided information on clinical outcomes. The mean total haemorrhage growth was 5.9 ml (SD 26.8) and 8.1 mL (SD 29.2) in the tranexamic acid and placebo groups respectively (adjusted difference –3.8 mL (95% confidence interval −11.5 to 3.9)). New focal cerebral ischaemic lesions occurred in 6 (5%) patients in the tranexamic acid group versus 12 (9%) in the placebo group (adjusted odds ratio 0.51 (95% confidence interval 0.18 to 1.44)). There were 14 (11%) deaths in the tranexamic acid group and 24 (18%) in the placebo group (adjusted odds ratio 0.47 (0.21 to 1.04)).
Conclusions This trial shows that neither moderate benefits nor moderate harmful effects of tranexamic acid in patients with traumatic brain injury can be excluded. However, the analysis provides grounds for further clinical trials evaluating the effect of tranexamic acid in this population.
Trial registration ISRCTN86750102.
The database programming was carried out by Tony Brady of Sealed Envelope.
CRASH-2 Collaborators (Intracranial Bleeding Study)
Writing Committee: Pablo Perel (UK) (chair), Rustam Al-Shahi Salman (UK), Alfredo Constain (Colombia), Yashbir Dewan (India), Jorge Herrera (Colombia), Taemi Kawahara (UK), Anil P Lal (India), Jorge Mejía-Mantilla (Colombia), Carlos Morales (Colombia), Zoe Morris (UK), David Prieto-Merino (UK), P V Ramana (India), R R Ravi (India), Ian Roberts (UK), Peter Sandercock (UK), Haleema Shakur (UK), Joanna Wardlaw (UK). The Clinical Trials Unit had full access to all the data in the study and had final responsibility for the decision to submit for publication.
India Collaborators: Anil P Lal, Natasha Gohain (Aditya Neuroscience Centre and Sanjivani Hospital); P V Ramana (Care Hospital); Yashbir Dewan, Sarvpreet Singh Grewal, Pradipta Tripathy (Christian Medical College); RR Ravi, S Raja, Anand Doshi (Medical Trust Hospital); Prakash Khetan (Jeevan Jyoti Hospital).
Colombian Collaborators: Carlos Morales, Santiago Naranjo (University of Antioquia, Hospital Universitario San Vicente de Paul); Alfredo Constain, Edwin Vazquez Salazar (Hospital Pablo Tobon Uribe); Jorge Herrera, Liliana Caicedo (Hospital San José de Popayán); Jorge Mejía-Mantilla, Ana MariaVarela (Fundación Valle del Lili).
UK Coordinating Team: Eni Balogun (clinical trials associate), Lin Barnetson (data manager), Collette Barrow (assistant trials administrator), Matthew Berle (trials assistant), Lisa Cook (assistant trials manager), Avni Gadhiya (data assistant), Taemi Kawahara (assistant trials manager), Pablo Perel (clinical lecturer), Maria Ramos (trials administrator), Ian Roberts (clinical coordinator), Chris Rubery (data assistant), Haleema Shakur (senior lecturer), Cynthia To (data assistant) (London School of Hygiene & Tropical Medicine); Rustam Al-Shahi Salman, Zoe Morris, David Perry, Peter Sandercock, Joanna Wardlaw (University of Edinburgh).
Steering Committee: Ian Franklin (chair), Brigitte Chaudhry, Tim Coats, Charles Deakin, Steve Goodacre, BJ Hunt, David Meddings, Richard Peto, Ian Roberts, Peter Sandercock.
Funding: The CRASH-2 study was funded by the UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation. This sub-study was funded by the UK Health Technology Assessment programme (06/303/20). Rustam Al-Shahi Salman was funded by a UK MRC clinician scientist fellowship. Joanna Wardlaw was funded by the Scottish Funding Council through the SINAPSE Collaboration (Scottish Imaging Network, A Platform for Scientific Excellence).
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: the submitted work was funded by the UK Health Technology Assessment programme (06/303/20), Rustam Al-Shahi Salman was funded by a UK MRC clinician scientist fellowship, Joanna Wardlaw was funded by the Scottish Funding Council; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Data sharing: Full information on accessing the data from this trial is available via freeBIRD (free Bank of Injury and emergency Research Data), a data repository hosted by the Clinical Trials Unit, London School of Hygiene and Tropical Medicine, at http://ctu2.lshtm.ac.uk/freebird.
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