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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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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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Ethnic groups”„Jews, by country of origin and age”„Minority Communities in Israel: Background & Overview”„Israel”„Language in Israel”„Selected Data from the 2011 Social Survey on Mastery of the Hebrew Language and Usage of Languages”„Religions”„5 facts about Israeli Druze, a unique religious and ethnic group”„Israël”Israel Country Study Guide„Haredi city in Negev – blessing or curse?”„New town Harish harbors hopes of being more than another Pleasantville”„List of localities, in alphabetical order”„Muncitorii români, doriți în Israel”„Prietenia româno-israeliană la nevoie se cunoaște”„The Higher Education System in Israel”„Middle East”„Academic Ranking of World Universities 2016”„Israel”„Israel”„Jewish Nobel Prize Winners”„All Nobel Prizes in Literature”„All Nobel Peace Prizes”„All Prizes in Economic Sciences”„All Nobel Prizes in Chemistry”„List of Fields Medallists”„Sakharov Prize”„Țara care și-a sfidat "destinul" și se bate umăr la umăr cu Silicon Valley”„Apple's R&D center in Israel grew to about 800 employees”„Tim Cook: Apple's Herzliya R&D center second-largest in world”„Lecții de economie de la Israel”„Land use”Israel Investment and Business GuideA Country Study: IsraelCentral Bureau of StatisticsFlorin Diaconu, „Kadima: Flexibilitate și pragmatism, dar nici un compromis în chestiuni vitale", în Revista Institutului Diplomatic Român, anul I, numărul I, semestrul I, 2006, pp. 71-72Florin Diaconu, „Likud: Dreapta israeliană constant opusă retrocedării teritoriilor cureite prin luptă în 1967", în Revista Institutului Diplomatic Român, anul I, numărul I, semestrul I, 2006, pp. 73-74MassadaIsraelul a crescut in 50 de ani cât alte state intr-un mileniuIsrael Government PortalIsraelIsraelIsraelmmmmmXX451232cb118646298(data)4027808-634110000 0004 0372 0767n7900328503691455-bb46-37e3-91d2-cb064a35ffcc1003570400564274ge1294033523775214929302638955X146498911146498911

Кастелфранко ди Сопра Становништво Референце Спољашње везе Мени за навигацију43°37′18″ СГШ; 11°33′32″ ИГД / 43.62156° СГШ; 11.55885° ИГД / 43.62156; 11.5588543°37′18″ СГШ; 11°33′32″ ИГД / 43.62156° СГШ; 11.55885° ИГД / 43.62156; 11.558853179688„The GeoNames geographical database”„Istituto Nazionale di Statistica”проширитиууWorldCat156923403n850174324558639-1cb14643287r(подаци)