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Lancet. 2010 Jul 3;376(9734):23-32. doi: 10.1016/S0140-6736(10)60835-5. Epub 2010 Jun 14.

Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial.



CRASH-2 trial collaborators, Shakur H, Roberts I, Bautista R, Caballero J, Coats T, Dewan Y, El-Sayed H, Gogichaishvili T, Gupta S, Herrera J, Hunt B, Iribhogbe P, Izurieta M, Khamis H, Komolafe E, Marrero MA, Mejía-Mantilla J, Miranda J, Morales C, Olaomi O, Olldashi F, Perel P, Peto R, Ramana PV, Ravi RR, Yutthakasemsunt S.


Collaborators (570)


Dakubo J, Gogichaishvili T, Golden N, Izurieta M, Khamis H, Komolafe E, Loría-Castellanos J, Mejía-Mantilla J, Miranda J, Muñoz A, Mutiso V, Okwen P, Ortiz Z, Pascual M, Ravi R, Roslani A, Trenkler S, Volpi A, Yutthakasemsunt S, Roberts I, Shakur H, Perel P, Barnetson L, Ramos M, Cook L, Kawahara T, Balogun E, Berle M, Barrow C, Brady T, Rubery C, Wayte J, To C, Franklin I, Chaudhry B, Coats T, Deakin C, Goodacre S, Hunt B, Meddings D, Peto R, Roberts I, Sandercock P, Roberts I, Shakur H, Coats T, Edwards P, Hunt B, Ramos M, Collins R, Grant A, Myburgh J, Baxter A, Olldashi F, Kerçi M, Zhurda T, Ruçi K, Banushi A, Traverso MS, Jiménez J, Balbi J, Dellera C, Svampa S, Quintana G, Piñero G, Teves J, Seppelt I, Mountain D, Balogh Z, Zaman M, Druwé P, Rutsaert R, Mazairac G, Pascal F, Yvette Z, Chancellin D, Okwen P, Djokam-Liapoe J, Jangwa E, Mbuagbaw L, Fointama N, Pascal N, Baillie F, Jiang JY, Gao GY, Bao YH, Morales C, Sierra J, Naranjo S, Correa C, Gómez C, Herrera J, Caicedo L, Rojas A, Pastas H, Miranda H, Constaín A, Perdomo M, Muñoz D, Duarte A, Vásquez E, Ortiz C, Ayala B, Delgado H, Benavides G, Rosero L, Mejía-Mantilla J, Varela A, Calle M, Castillo J, García A, Ciro C, Villa C, Panesso R, Flórez L, Gallego A, Puentes-Manosalva F, Medina L, Márquez K, Romero AR, Hernández R, Martínez J, Gualteros W, Urbina Z, Velandia J, Benítez F, Trochez A, Villarreal A, Pabón P, Delgado H, López H, Quintero L, Rubiano A, Tamayo J, Piñera M, Navarro Z, Rondón D, Bujan B, Palacios L, Martínez D, Hernández Y, Fernández Y, Casola E, Delgado R, Herrera C, Arbolaéz M, Domínguez M, Iraola M, Rojas O, Enseñat A, Pastrana I, Rodríguez D, de la Campa SA, Fortún T, Larrea M, Aragón L, Madrazo A, Svoboda P, Izurieta M, Daccach A, Altamirano M, Ortega A, Cárdenas B, González L, Ochoa M, Ortega F, Quichimbo F, Guiñanzaca J, Zavala I, Segura S, Jerez J, Acosta D, Yánez F, Camacho R, Khamis H, Shafei H, Kheidr A, Nasr H, Mosaad M, Rizk S, El Sayed H, Moati T, Hokkam E, Amin M, Lowis H, Fawzy M, Bedir N, Aldars M, Rodríguez V, Tobar J, Alvarenga J, Shalamberidze B, Demuria E, Rtveliashvili N, Chutkerashvili G, Dotiashvili D, Gogichaishvili T, Ingorokva G, Kazaishvili D, Melikidze B, Iashvili N, Tomadze G, Chkhikvadze M, Khurtsidze L, Lomidze Z, Dzagania D, Kvachadze N, Gotsadze G, Kaloiani V, Kajaia N, Dakubo J, Naaeder S, Sowah P, Yusuf A, Ishak A, Selasi-Sefenu P, Sibiri B, Sarpong-Peprah S, Boro T, Bopaiah K, Shetty K, Subbiah R, Mulla L, Doshi A, Dewan Y, Grewal S, Tripathy P, Mathew J, Gupta B, Lal A, Choudhury M, Gupta S, Gupta S, Chug A, Pamidimukkala V, Jagannath P, Maharaj M, Vommi R, Gudipati N, Chhang WH, Patel P, Suthar N, Banker D, Patel J, Dharap S, Kamble R, Patkar S, Lohiya S, Saraf R, Kumar D, Parihar S, Gupta R, Mangual R, Alagumuthu, Kooper D, Mohapatra C, David S, Rajaleelan W, Appas, Pangi A, Saraf V, Chikareddy S, Mankar S, Golhar A, Sakhare R, Wagh N, Lal A, Hazarika D, Chaudhuri P, Ketan P, Purohit G, Purohit Y, Pandya M, Gupta R, Kiran S, Walia S, Goyal S, Goyal S, Goyal S, Gupta S, Attri A, Sharma R, Oberai A, Oberai M, Oberoi S, Tripathi GK, Peettakkandy V, Karuthillath P, Vadakammuriyil P, Pol J, Pol S, Saste M, Raul S, Tiwari S, Nelly N, Chidambaram M, Kollengode V, Thampan S, Rajan S, Rajan S, Raju S, Sharma R, Babu SV, Sumathi C, Chatterjee P, Agarwal A, Magar H, Magar M, Singh M, Gupta D, Lal A, Haloi K, Sagdeo V, Giri P, Verma N, Jariwala R, Goti A, Prabhu-Gaonkar A, Utagi S, Joshi M, Agrawal R, Sharma G, Saini G, Tewari V, Yadav Y, Parihar V, Venkataramana N, Rao S, Reddy N, Chander SG, Hathila V, Das V, Agaja K, Purohit A, Lahari A, Bhagchandani R, Vidyasagar B, Sachan PK, Das T, Vyas S, Bhattacharjee S, Sancheti P, Manoj T, Moideen M, Pansey K, Chandrasekaran VP, Saikia K, Tata H, Vhora S, Shah A, Rangad G, Rajasekaran S, Shankarlal ST, Devadoss S, Saleem M, Pillay H, Hazarika Z, Deshmukh P, Murugappan SP, Jaiswal A, Vangani D, Modha P, Chonzik C, Praveen M, Sethurayar V, Ipe S, Shetty N, Shah A, Gupta RP, Jain V, Shah K, Dwikoryanto M, Golden N, Atmadjaya K, Wiargitha K, Sudiasa K, Suwedagatha G, Bal'afif F, Budipramana V, Tabrani, Lemuel A, Chandra S, Ama F, Sherafatkazemzadeh E, Moradi E, Sheikhi A, Ziaee A, Fanaei A, Hajinasrollah E, Amini A, Mohammad B, Hadi N, Perone G, de Peri E, Volpi A, Johnson J, Abe M, Mutiso V, Okanga B, Ojuka D, Abdullah B, Rahman H, Noh Y, Jamaluddin S, Dawal H, Roslani A, Law CW, Devashanti P, Wahab Y, Velaiutham S, Dato R, Loría J, Montes E, Gómez E, Cazales V, Bautista P, Bautista R, Ahumada D, Hernández E, Velásquez G, Ortega P, Lira G, Estrada F, Martínez J, Martínez J, Casasola J, Olaomi O, Abubakar Y, Apollo K, Badejo O, Ihekire O, Iribhogbe P, Oludiran O, Obeta E, Okojie C, Udefiagbon E, Komolafe E, Olaleye P, Uzochukwu T, Onakpoya U, Dongo A, Uhunmwagho O, Eighemerio E, Morgan E, Thanni L, Afolabi A, Akinola T, Ademola A, Akute O, Khalid L, Abubakar L, Aminu M, Ogirima M, Attansey A, Michael D, Aremu O, Olugbenga O, Ukpong U, Salman Y, Obianyo N, Ani C, Ezeadawi R, Kehinde O, Olaide A, Jogo A, Bitto T, Anyanwu S, Mbonu O, Oludara M, Somoye M, Shehu B, Ismail N, Katchy A, Ndoma-Egba R, Grace-Inah N, Songden Z, Abdulraheem A, Otu A, Nottidge T, Inyang D, Idiapho D, Giebel H, Hassan R, Adisa A, Akinkuolie A, Okam K, Musa A, Falope I, Eze J, Caballero J, Azabache W, Salirrosas O, Soto A, Torres E, Ramírez G, Pérez M, Malca C, Velez J, Yepez R, Yupanqui H, Lagos P, Rodriguez D, Flores J, Moya A, Barrionuevo A, Gonzales-Portillo M, Nunez E, Eldawlatly A, Al Naami M, Delvi B, Alyafi W, Djurovic B, Ng I, Yaghi A, Laincz A, Trenkler S, Valky J, Modiba M, Legodi P, Rangaka T, Wallis W, Muñoz A, Serrano A, Misis M, Rubi M, de la Torre V, Ellawala R, Wijeratna S, Gunaratna L, Wijayanayaka C, Nungu K, Haonga B, Mtapa G, Yutthakasemsunt S, Kittiwattanagul W, Piyavechvirat P, Impool T, Thummaraj S, Salaeh R, Tangchitvittaya S, Wattanakrai K, Soonthornthum C, Jiravongbunrod T, Meephant S, Subsompon P, Pensuwan P, Chamnongwit W, Jerbi Z, Cherif A, Nash M, Harris T, Banerjee J, Freij R, Kendall J, Moore S, Townend W, Cottingham R, Becker D, Lloyd S, Burdett-Smith P, Mirza K, Webster A, Brady S, Grocutt A, Thurston J, Lecky F, Goodacre S, Mulla Y, Sakala D, Chengo C.




Abstract



BACKGROUND:


Tranexamic acid can reduce bleeding in patients undergoing elective surgery. We assessed the effects of early administration of a short course of tranexamic acid on death, vascular occlusive events, and the receipt of blood transfusion in trauma patients.


METHODS:


This randomised controlled trial was undertaken in 274 hospitals in 40 countries. 20 211 adult trauma patients with, or at risk of, significant bleeding were randomly assigned within 8 h of injury to either tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator. Both participants and study staff (site investigators and trial coordinating centre staff) were masked to treatment allocation. The primary outcome was death in hospital within 4 weeks of injury, and was described with the following categories: bleeding, vascular occlusion (myocardial infarction, stroke and pulmonary embolism), multiorgan failure, head injury, and other. All analyses were by intention to treat. This study is registered as ISRCTN86750102, Clinicaltrials.govNCT00375258, and South African Clinical Trial RegisterDOH-27-0607-1919.


FINDINGS:


10 096 patients were allocated to tranexamic acid and 10 115 to placebo, of whom 10 060 and 10 067, respectively, were analysed. All-cause mortality was significantly reduced with tranexamic acid (1463 [14.5%] tranexamic acid group vs 1613 [16.0%] placebo group; relative risk 0.91, 95% CI 0.85-0.97; p=0.0035). The risk of death due to bleeding was significantly reduced (489 [4.9%] vs 574 [5.7%]; relative risk 0.85, 95% CI 0.76-0.96; p=0.0077).


INTERPRETATION:


Tranexamic acid safely reduced the risk of death in bleeding trauma patients in this study. On the basis of these results, tranexamic acid should be considered for use in bleeding trauma patients.


FUNDING:


UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation.






Comment in



  • Antifibrinolytic therapy: new data and new concepts. [Lancet. 2010]


  • The use of tranexamic acid for trauma patients? [CJEM. 2012]


  • Tranexamic acid for trauma. [Lancet. 2010]


  • Tranexamic acid for trauma. [Lancet. 2010]


  • Tranexamic acid for trauma. [Lancet. 2010]


  • Tranexamic acid effects in trauma patients with significant hemorrhage. [J Am Coll Surg. 2012]



PMID:
20554319
DOI:
10.1016/S0140-6736(10)60835-5

[Indexed for MEDLINE]


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Publication types, MeSH terms, Substances, Secondary source IDs, Grant support



Publication types


  • Multicenter Study

  • Randomized Controlled Trial

  • Research Support, Non-U.S. Gov't

MeSH terms


  • Adult

  • Antifibrinolytic Agents/therapeutic use*

  • Blood Transfusion*

  • Female

  • Hemorrhage/drug therapy*

  • Hemorrhage/etiology

  • Hemorrhage/mortality

  • Hemorrhage/therapy

  • Humans

  • Male

  • Thrombosis/etiology

  • Thrombosis/prevention & control*

  • Tranexamic Acid/therapeutic use*

  • Wounds and Injuries/complications*

Substances


  • Antifibrinolytic Agents

  • Tranexamic Acid

Secondary source IDs


  • ClinicalTrials.gov/NCT00375258

  • ISRCTN/ISRCTN86750102

Grant support


  • 06/303/20/Department of Health/United Kingdom

  • HTA/06/303/20/Department of Health/United Kingdom

  • T32 GM008315/GM/NIGMS NIH HHS/United States





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Full Text Sources


  • Elsevier Science

  • ClinicalKey

Other Literature Sources


  • See the articles recommended by F1000Prime's Faculty of more than 8,000 leading experts in Biology and Medicine. - Faculty of 1000

Medical


  • ClinicalTrials.gov

  • Blood Transfusion and Donation - MedlinePlus Health Information

  • Wounds and Injuries - MedlinePlus Health Information

  • Blood Clots - MedlinePlus Health Information

  • Bleeding - MedlinePlus Health Information
















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