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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Understanding the neuroprotective effect of tranexamic acid: an exploratory analysis of the CRASH-3 randomised trial
Critical Care, Volume 24, No. 1, Article 560, Year 2020
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Description
Background: The CRASH-3 trial hypothesised that timely tranexamic acid (TXA) treatment might reduce deaths from intracranial bleeding after traumatic brain injury (TBI). To explore the mechanism of action of TXA in TBI, we examined the timing of its effect on death. Methods: The CRASH-3 trial randomised 9202 patients within 3 h of injury with a GCS score ≤ 12 or intracranial bleeding on CT scan and no significant extracranial bleeding to receive TXA or placebo. We conducted an exploratory analysis of the effects of TXA on all-cause mortality within 24 h of injury and within 28 days, excluding patients with a GCS score of 3 or bilateral unreactive pupils, stratified by severity and country income. We pool data from the CRASH-2 and CRASH-3 trials in a one-step fixed effects individual patient data meta-analysis. Results: There were 7637 patients for analysis after excluding patients with a GCS score of 3 or bilateral unreactive pupils. Of 1112 deaths, 23.3% were within 24 h of injury (early deaths). The risk of early death was reduced with TXA (112 (2.9%) TXA group vs 147 (3.9%) placebo group; risk ratio [RR] RR 0.74, 95% CI 0.58–0.94). There was no evidence of heterogeneity by severity (p = 0.64) or country income (p = 0.68). The risk of death beyond 24 h of injury was similar in the TXA and placebo groups (432 (11.5%) TXA group vs 421 (11.7%) placebo group; RR 0.98, 95% CI 0.69–1.12). The risk of death at 28 days was 14.0% in the TXA group versus 15.1% in the placebo group (544 vs 568 events; RR 0.93, 95% CI 0.83–1.03). When the CRASH-2 and CRASH-3 trial data were pooled, TXA reduced early death (RR 0.78, 95% CI 0.70–0.87) and death within 28 days (RR 0.88, 95% CI 0.82–0.94). Conclusions: Tranexamic acid reduces early deaths in non-moribund TBI patients regardless of TBI severity or country income. The effect of tranexamic acid in patients with isolated TBI is similar to that in polytrauma. Treatment is safe and even severely injured patients appear to benefit when treated soon after injury. Trial registration: ISRCTN15088122, registered on 19 July 2011; NCT01402882, registered on 26 July 2011. © 2020, The Author(s).
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC7657351/bin/13054_2020_3243_MOESM1_ESM.docx
Authors & Co-Authors
Brenner, Amy
United Kingdom, London
London School of Hygiene & Tropical Medicine
Belli, Antonio
United Kingdom, Birmingham
University of Birmingham
Chaudhri, Rizwana
Pakistan, Islamabad
Shifa Tameer-e-millat University
Coats, Timothy J.
United Kingdom, Leicester
University of Leicester
Frimley, Lauren
United Kingdom, London
London School of Hygiene & Tropical Medicine
Jamaluddin, Sabariah Faizah Bt
Malaysia, Shah Alam
Universiti Teknologi Mara
Jooma, Rashid A.
Pakistan, Karachi
The Aga Khan University Hospital
Mansukhani, Raoul
United Kingdom, London
London School of Hygiene & Tropical Medicine
Sandercock, Peter A.G.
United Kingdom, Edinburgh
The University of Edinburgh
Shakur-Still, Haleema
United Kingdom, London
London School of Hygiene & Tropical Medicine
Shokunbi, Mathew Temitayo
Nigeria, Ibadan
University College Hospital, Ibadan
Nigeria, Ibadan
College of Medicine, University of Ibadan
Roberts, Ian
United Kingdom, London
London School of Hygiene & Tropical Medicine
Roberts, Ian G.
Unknown Affiliation
Aeron-Thomas, Amy S.
Unknown Affiliation
Chaudary, Muhammad Anwar
Unknown Affiliation
Javaid, Kiran
Unknown Affiliation
Kayani, Aasia
Unknown Affiliation
Leech, Caroline
Unknown Affiliation
Mahmood, Khalid
Unknown Affiliation
Noor, Julina Md
Unknown Affiliation
Mejia-Mantilla, Jorge Humberto
Unknown Affiliation
Moss, Phil S.
Unknown Affiliation
Pott, Jason D.
Unknown Affiliation
Sandercock, Peter A.G.
Unknown Affiliation
Shokunbi, Temitayo
Unknown Affiliation
Vallecilla, Liliana
Unknown Affiliation
Hartzenberg, Henry Benjamin
Unknown Affiliation
Joshipura, Manjul K.
Unknown Affiliation
Perel, Pablo A.
Unknown Affiliation
Clarke, Michael J.
Unknown Affiliation
Ohaegbulam, Samuel Chukwunonyerem
Unknown Affiliation
Rodgers, Anthony J.
Unknown Affiliation
Brady, Tony
Unknown Affiliation
Dewan, Yashbir
Unknown Affiliation
Edwards, Phil James
Unknown Affiliation
Komolafe, Edward O.
Unknown Affiliation
Arribas, Monica
Unknown Affiliation
Austin, Emma
Unknown Affiliation
Balogun, Eni
Unknown Affiliation
Barneston, Lin
Unknown Affiliation
Barrow, Collette
Unknown Affiliation
Beaumont, Danielle D.
Unknown Affiliation
Benyahia, Myriam
Unknown Affiliation
Brooks, Imogen
Unknown Affiliation
Cargill, Madeleine
Unknown Affiliation
Carrington, Laura
Unknown Affiliation
Cook, Lisa
Unknown Affiliation
Cornu-Hewitt, Beatrice
Unknown Affiliation
Geer, Amber
Unknown Affiliation
Gilbert, Daniel
Unknown Affiliation
Gilliam, Catherine
Unknown Affiliation
Gil Onandia, Julio
Unknown Affiliation
Hetherington, Daniel
Unknown Affiliation
Howe, Courtenay
Unknown Affiliation
Hughes, Carly A.
Unknown Affiliation
I’anson, David
Unknown Affiliation
Jackson, Robert L.
Unknown Affiliation
Joshi, Miland
Unknown Affiliation
Kansagra, Sneha
Unknown Affiliation
Kawahara, Taemi
Unknown Affiliation
Ker, Katharine
Unknown Affiliation
Kostrov, Sergey
Unknown Affiliation
Mahmood, Abda
Unknown Affiliation
Miah, Hakim
Unknown Affiliation
Ndungu, Bernard
Unknown Affiliation
Needham, Kelly
Unknown Affiliation
Okusi, Cecilia
Unknown Affiliation
Outtandy, Aroudra
Unknown Affiliation
Pardinaz-Solis, Raul
Unknown Affiliation
Pearson, Daniel
Unknown Affiliation
Pepple, Tracey
Unknown Affiliation
Pisani, Claude
Unknown Affiliation
Prieto-Merino, David
Unknown Affiliation
Prowse, Danielle
Unknown Affiliation
Quashi, Nigel
Unknown Affiliation
Quinn, Anna
Unknown Affiliation
Ramos, Maria
Unknown Affiliation
Reid, Mia
Unknown Affiliation
Roukas, Chris
Unknown Affiliation
Scrapa, Giulia
Unknown Affiliation
Squires, Chelci
Unknown Affiliation
Tanner, Jemma
Unknown Affiliation
Thayne, Andrew
Unknown Affiliation
Vidaurre, Lesley
Unknown Affiliation
Woods, Elizabeth
Unknown Affiliation
Fawole, Bukola O.
Unknown Affiliation
Adetayo, Olusade
Unknown Affiliation
Okunade, Olujide A.
Unknown Affiliation
Gogichaishvili, Tamar
Unknown Affiliation
de Los Angeles Munoz-Sanchez, Maria
Unknown Affiliation
Olldashi, Fatos
Unknown Affiliation
Krishnan, Satish
Unknown Affiliation
Djientcheu, Vincent De Paul
Unknown Affiliation
Castellanos, Jorge Loria
Unknown Affiliation
Rasulo, Frank Anthony
Unknown Affiliation
Hama, Qadamkhear
Unknown Affiliation
Mulla, Yakub
Unknown Affiliation
Florian, Ioan Stefan
Unknown Affiliation
Tobar, Juan
Unknown Affiliation
Khamis, Hussein
Unknown Affiliation
Deasy, Conor
Unknown Affiliation
Wellsh, Bobby M.
Unknown Affiliation
Williams-Johnson, Jean A.
Unknown Affiliation
Chandra, Susilo
Unknown Affiliation
Mutiso, Vincent Muoki
Unknown Affiliation
Hussain, Shahzad D.
Unknown Affiliation
Ahmad, Usman
Unknown Affiliation
Asif, Muhammad
Unknown Affiliation
Ain, Quratul Ul
Unknown Affiliation
Khan, Abdus Salam
Unknown Affiliation
Sharif, Salman Yousuf
Unknown Affiliation
Harris, Tim R.E.
Unknown Affiliation
Lecky, Fiona Elizabeth
Unknown Affiliation
Wilson, Mark H.
Unknown Affiliation
Boyle, Adrian
Unknown Affiliation
Hardwick, Susie
Unknown Affiliation
Coffey, Frank
Unknown Affiliation
Kehoe, Anthony D.
Unknown Affiliation
Bulters, Diederik Olivier
Unknown Affiliation
Zolnourian, Ardalan H.
Unknown Affiliation
Body, Richard M.
Unknown Affiliation
Cottingham, Rowland L.
Unknown Affiliation
Maritz, David
Unknown Affiliation
Jamaluddin, Sabariah Faiwah
Unknown Affiliation
Noor, Julina Md
Unknown Affiliation
Wong, Kwanhathai Darin
Unknown Affiliation
Yang, Chia Boon
Unknown Affiliation
Mohidin, Mohd Amin Bin
Unknown Affiliation
Tomadze, Gia
Unknown Affiliation
Múñoz-Sánchez, María Ángeles
Unknown Affiliation
Ukwu, Nancy
Unknown Affiliation
Oseni, Abidemi Wasiu
Unknown Affiliation
Adebayo, Bamidele Oludele
Unknown Affiliation
Malomo, Adefolarin Obanisola
Unknown Affiliation
Tiamiyu, Liadi Olanrewaju
Unknown Affiliation
Adekanmbi, Adefisayo Ayoade
Unknown Affiliation
Thanni, Lateef O.A.
Unknown Affiliation
Olubodun, Ayodeji Bamidele
Unknown Affiliation
Komolafe, Edward Oluwole
Unknown Affiliation
Owagbemi, Oluwafemi F.
Unknown Affiliation
Durodola, Adewumi O.
Unknown Affiliation
Udoffa, Ukpong S.
Unknown Affiliation
Dongo, Andrew E.
Unknown Affiliation
Ekpemiro, Uchechi Chukwudike
Unknown Affiliation
Anyanwu, Stanley Nnamdi Chinedu
Unknown Affiliation
Aigoro, Nafiu O.
Unknown Affiliation
Mezue, Wilfred Chukwuemeka
Unknown Affiliation
Shilong, Danaan J.
Unknown Affiliation
Azeez, Abiodun Luqman
Unknown Affiliation
Babalola, Olakunle Fatai
Unknown Affiliation
Obande, Joseph O.
Unknown Affiliation
Morales Uribe, Carlos H.
Unknown Affiliation
Naranjo, Santiago
Unknown Affiliation
Shoko, Tomohisa
Unknown Affiliation
Otomo, Yasuhiro
Unknown Affiliation
Moumi, Mireille Georgette
Unknown Affiliation
Fondop, Joseph
Unknown Affiliation
Stock, Simon E.
Unknown Affiliation
Ilunga, Ali
Unknown Affiliation
Mulenga, Jonathan
Unknown Affiliation
Pleş, Horia
Unknown Affiliation
Florian, Ștefan Ioan
Unknown Affiliation
Kiboi, Julius Githinji
Unknown Affiliation
Statistics
Citations: 21
Authors: 163
Affiliations: 9
Identifiers
Doi:
10.1186/s13054-020-03243-4
ISSN:
13648535
Research Areas
Genetics And Genomics
Health System And Policy
Violence And Injury
Study Design
Exploratory Study
Study Approach
Systematic review