Abstract
Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial. Funding: UK National Institute for Health Research Health Technology Assessment Programme.
| Original language | English |
|---|---|
| Pages (from-to) | 1927-1936 |
| Number of pages | 10 |
| Journal | The Lancet |
| Volume | 395 |
| Issue number | 10241 |
| DOIs | |
| Publication status | Published - 20 Jun 2020 |
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In: The Lancet, Vol. 395, No. 10241, 20.06.2020, p. 1927-1936.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT)
T2 - an international randomised, double-blind, placebo-controlled trial
AU - Roberts, Ian
AU - Shakur-Still, Haleema
AU - Afolabi, Adefemi
AU - Akere, Adegboyega
AU - Arribas, Monica
AU - Brenner, Amy
AU - Chaudhri, Rizwana
AU - Gilmore, Ian
AU - Halligan, Kenneth
AU - Hussain, Irshad
AU - Jairath, Vipul
AU - Javaid, Kiran
AU - Kayani, Aasia
AU - Lisman, Ton
AU - Mansukhani, Raoul
AU - Mutti, Muttiullah
AU - Arif Nadeem, Muhammad
AU - Pollok, Richard
AU - Simmons, Jonathan
AU - Soomro, Majid
AU - Stanworth, Simon
AU - Veitch, Andrew
AU - Hawkey, Christopher
AU - Cuzick, Jack
AU - Henry, David
AU - Metcalfe, Chris
AU - Gray, Richard
AU - Barkun, Alan
AU - David, Suresh
AU - Devereaux, Philip
AU - Brady, Tony
AU - Coats, Timothy
AU - Edwards, Phil
AU - Ker, Katharine
AU - Manno, Daniela
AU - Austin, Emma
AU - Bal, Kiran
AU - Balogun, Eni
AU - Barrow, Collette
AU - Beaumont, Danielle
AU - Benyahia, Myriam
AU - Brooks, Imogen
AU - Cargill, Madeleine
AU - Carrington, Laura
AU - Frimley, Lauren
AU - Geer, Amber
AU - Gilbert, Daniel
AU - Gilliam, Catherine
AU - Gil Onandia, Julio
AU - Golfi, Nayia
AU - Hetherington, Daniel
AU - Howe, Courtenay
AU - Hughes, Carolyn
AU - I'anson, David
AU - Jackson, Rob
AU - Joshi, Miland
AU - Kansagra, Sneha
AU - Kawahara, Taemi
AU - Kostrov, Sergey
AU - Miah, Hakim
AU - Ndungu, Bernard
AU - Needham, Kelly
AU - Outtandy, Aroudra
AU - Pearson, Daniel
AU - Pepple, Tracey
AU - Prowse, Danielle
AU - Quashi, Nigel
AU - Quinn, Anna
AU - Ramos, Maria
AU - Ranopa, Laura
AU - Reid, Mia
AU - Roukas, Chris
AU - Squires, Chelci
AU - Tanner, Jemma
AU - Thayne, Andrew
AU - Uddin, Ruhama
AU - Fawole, Bukola
AU - Bello, Folasade Adenike
AU - Olayemi, Oladapo
AU - Okunade, Olujide
AU - Adetayo, Olusade
AU - Khamis, Hussein
AU - Shukri Bin Jahit, Mohammad
AU - Gogichaishvili, Tamar
AU - Mateescu, Radu Bogdan
AU - Adhikaree, Ajay
AU - Abdo, Abdelmounem Eltayeib
AU - Zaher, Mohammad
AU - Deasy, Conor
AU - Alvarez Gregori, Joaquin
AU - Wellsh, Bobby
AU - Lawton, Luke
AU - Kamath, Raghavendra
AU - Barry, Adrian
AU - Carpio, Racquel
AU - Finney, Kay
AU - Maguire, Holly
AU - James, Martin
AU - Coffey, Frank
AU - Gough, Chris
AU - Sawers, Lisa
AU - Thi, Aye Aye
AU - Burnett, Claire
AU - Jacques, Nicola
AU - Murray, Victoria
AU - Jarman, Heather
AU - Lambe, Christine
AU - Rounding, Sarah
AU - Tucker, Simon
AU - Al-Idari, Romaih
AU - Guest, Samuel
AU - Stoddard, Emma
AU - Yeo, David
AU - Bergin, Colin
AU - Hardy, Elaine
AU - Thunder, Joanne
AU - Jhalli, Paul
AU - Hartley, Edward
AU - Jarvis, Catherine
AU - Swann, Carly
AU - Reed, Matthew
AU - Gallagher, Bernadette
AU - Grahamslaw, Julia
AU - O'Brien, Rachel
AU - Harris, Timothy
AU - Bellhouse, Geoffrey
AU - Boulton, Olivia
AU - Skene, Imogen
AU - Stanley, Adrian
AU - Johnstone, Janet
AU - Maguire, Donogh
AU - Thornton, Susan
AU - Banks, Matthew
AU - Bercades, Georgia
AU - Marks, Daniel
AU - Ryu, Jung
AU - Dowty, Claire
AU - Pott, Jason
AU - East, James
AU - Bailey, Adam
AU - Beer, Sally
AU - Davies, Sian
AU - Appelboam, Andrew
AU - Mackle, Daisy
AU - Small, Jennifer
AU - Vorwerk, Christiane
AU - Atkins, Rachel
AU - Bradbury, Isobel
AU - Bryceland, Catriona
AU - McClelland, Lisa
AU - Thomas, Martin
AU - Clayton, Kate
AU - Michael, Angiy
AU - Haig, Stephen
AU - Al-Nahhas, Saif
AU - Godfrey, Tim
AU - Boger, Philip
AU - Comer, Rachel
AU - Watkins, Barbara
AU - Afolabi, Ola
AU - Afzal, Shazad
AU - Cowton, Amanda
AU - Everett, Simon
AU - Fazakerley, Ruth
AU - Onoviran, Felicia
AU - Snook, Jonathon
AU - Berry, Jackie
AU - Simpson, Diane
AU - Keep, Jeff
AU - Cotton, Hannah
AU - Helyar, Sinead
AU - Rutter, Matthew
AU - Johnston, Tracey
AU - O'Rourke, Laura
AU - Chan, Louisa
AU - Tambellini, Joanna
AU - Trodd, Dawn
AU - Shutt, James
AU - Moreton, Sarah
AU - Oglesby, Abby
AU - Boyle, Adrian
AU - Haeger, Nicola
AU - Hardwick, Susie
AU - Kendall, Jason
AU - Faulkner, Beverley
AU - Worner, Ruth
AU - Hearnshaw, Sarah
AU - Doona, Mary
AU - Price, Maria
AU - Hunter, Laura
AU - Bell, Maggie
AU - Loureiro, Vania
AU - Kehoe, Anthony
AU - Jefferey, Alison
AU - Squire, Rosalyn
AU - Hartin, David
AU - Bell, Stephanie
AU - Newman, Alexandra
AU - Gagg, James
AU - Foot, Jayne
AU - Wakeford, Sue
AU - May, Gabrielle
AU - Bartram, Thomas
AU - Cumpstay, Paul
AU - Parker, Lucy
AU - Das, Rita
AU - Pahary, Sheik
AU - Wright, Gavin
AU - Butt, Georgina
AU - Christmas, Natasha
AU - Wilson, Sarah
AU - Ashfaq, Mohammed
AU - Chandler, Louise
AU - Demetriou, Carrie
AU - Kaye, Philip
AU - Carley, Simon
AU - Brown, Andrew
AU - Jones, Lucy
AU - Whileman, Amanda
AU - Greenaway, John
AU - Tregonning, Julie
AU - Kuhrt, Avril
AU - Goodacre, Steve
AU - Jones, John
AU - Owen, Charlotte
AU - Mitra, Anu
AU - Harper-Payne, Abby
AU - Trudgill, Nigel
AU - Hayes, Anne
AU - Butt, Faheem
AU - Clifford, Gayle
AU - Kinnon, Andrew
AU - Fowler, Susan
AU - Pillay, Kris
AU - Gidwani, Shweta
AU - McNair, Alistair
AU - Omer, Omer
AU - de Weymarn, Tanya
AU - Amin, Adnan
AU - Martin, Jane
AU - Mathieu, Nick
AU - Barnes, Simon
AU - Turvill, James
AU - Sweeting, Helen
AU - Draegebo, Morten
AU - McNaught, Marion
AU - Grocutt, Mandy
AU - Margalef, Jordi
AU - Humphrey, Julian
AU - Jackson, Richard
AU - Bellis, Fionn
AU - Hunt, Jane
AU - Stevenson, Alastair
AU - Watson, Nicholas
AU - Barden, Steven
AU - Paterson, Stuart
AU - Macdonald, Chris
AU - Hobday, David
AU - Orugun, Olu
AU - Allison, Andrew
AU - Dyer, Tristan
AU - McBride, Samuel
AU - Sawicki, Wojciech
AU - Rayner, Ben
AU - Flowerdew, Lynsey
AU - Barbour, Jamie
AU - Klein, Jason
AU - Hood, Stephen
AU - Palmer, Nicola
AU - de Wolff, Jacob
AU - Shenoy, Achuth
AU - Swallow, Peter
AU - Srirajaskanthan, Rajaventhan
AU - Arshad, Hamza
AU - Aslam, Naeem
AU - Bangash, Anam
AU - Qamar, Muhammad
AU - Zahoor, Haroon
AU - Arshad, Saba
AU - ain Ghalib, Quratul
AU - Hameed, Tehseen
AU - Saif, Tayyaba
AU - Shafi, Wajahat
AU - Ali, Abid
AU - Khan, Shehroze
AU - Muaaz, Muhammad
AU - Taj, Ahmad
AU - Ghafoor, Aamir
AU - Afridi, Aamir
AU - Ahmad, Mansoor
AU - Aslam, Mujahid
AU - Kumar, Sandeep
AU - Ali, Mohsin
AU - Bughio, Ubedullah
AU - Chang, Adil
AU - Shaikh, Sana
AU - Ahmad, Syed
AU - Ali, Zeeshan
AU - Waqar, Marium
AU - Mushir, Aiman
AU - Sattar, Sadaf
AU - Goraya, Saifullah
AU - Aslam, Sharmeen
AU - Fatima, Nighat
AU - Noreen, Saadia
AU - Saleem, Sheraz
AU - Rahman, Fazal
AU - Iqbal, Nadeem
AU - Khalid, Mohammad
AU - Riaz, Umar
AU - Umar, Muhammad
AU - Akhter, Tayyab
AU - Khan, Javaria
AU - Misbah, Noureen
AU - Afzal, Muhammad
AU - Kayani, Mobeen
AU - Shah, Syed
AU - Tarar, Shahida
AU - Khan, Sherbat
AU - Iqbal, Yasir
AU - Khan, Essa
AU - Reki, Maqbool
AU - Hussain, Tanveer
AU - Iqbal, Shafqat
AU - Khurram, Muhammad
AU - Shafi, Muhammad
AU - Shaikh, Abrar
AU - Ahmed, Aijaz
AU - Kumar, Ameet
AU - Sachdev, Pinkey
AU - Nasir, Khalid Mahmood
AU - Chaudhry, Zafar Iqbal
AU - Zubair, Muhammad
AU - Tayyab, Ghias
AU - Mushtaq, Junaid
AU - Nasir, Muhammad
AU - Khan, Amir
AU - Ali, Amjad
AU - Ali, Sajjad
AU - Uddin, Wasim
AU - Ahmed, Sohaib
AU - Kazmi, Tazaeen
AU - Channa, Saleh
AU - Aman, Adeeqa
AU - Shaikh, Mouzam
AU - Rizvi, Tahir
AU - Hussain, Amjad
AU - Baqai, Haider Zaigham
AU - Rasheed, Zakawat
AU - Khan, Abdus
AU - Irfan, Adeela
AU - Husain, Aamir
AU - Aslam, Asifa
AU - Yahya, Khalid
AU - Azhar, Salman
AU - Ul Haq, Mansoor
AU - Afzal, Adeel
AU - Imran, Muhammad
AU - Saeed, Iram
AU - Yusuf, Aasim
AU - Hassan, Mariam
AU - Marwat, Mumtaz
AU - Ishfaq, Muhammad
AU - Bashir, Tahir
AU - Kumar, Santosh
AU - Yaqoob, Sajjad
AU - Wahid, Abdul
AU - Fakoya, Tinuola
AU - Oke, Temitope
AU - Tejan, Edries
AU - Olaomi, Oluwole
AU - Badejo, Olawale
AU - Nnaemaka, Okafor
AU - Ukwu, Nancy
AU - Arowolo, Olukayode
AU - Aderounmu, Adewale
AU - Wuraola, Funmilola
AU - Ugiagbe, Rose
AU - Atiri, Alexander
AU - Eghaghe, Enadeghe
AU - Adekoya, Adeleke
AU - Tade, Adedayo Oluyomi
AU - Shonoiki, Olatunji
AU - Olatoke, Samuel
AU - Raji, Toafiq
AU - Ekwunife, Christopher
AU - Onyekpere, Chigozirim
AU - Ahmed, Adamu
AU - Muhammad, Daniyan
AU - Odeghe, Emuobor
AU - Lesi, Olufunmilayo
AU - Osueni, Azeberoje
AU - Samaila, Adamu
AU - Nahuche, Aminu
AU - Ajayi, Akande
AU - Dongo, Andrew
AU - Ijoma, Uchenna
AU - Adebanjo, Ademola Tolulope
AU - Igetei, Rufina
AU - Yilkudi, Monday
AU - Osisanya, Kehinde
AU - Okeke, Edith Nonyelum
AU - Enwere, Oguamanam Okezie
AU - Esmat, Serag
AU - Ashoush, Omar
AU - Naga, Mazen
AU - Nagy, Fady
AU - Saiid, Mostafa
AU - Shaker, Ahmed
AU - Helmy, Ashraf
AU - Saafan, Saafan
AU - Abdel Monem, Mohammed
AU - Din, Jiffre
AU - Azis, Khairul
AU - Brukan, Muhyuddin
AU - Singh, Sanjay
AU - Zakaria, Andee
AU - Farid, Shaik
AU - Hashim, Nizam
AU - Mafauzy, Masykurin
AU - Najmi, Wan
AU - Amri, Nil
AU - Yi, Xin
AU - Hisyam, Mohammad
AU - Ng, Elaine
AU - Ramli, Zuhrirahimi
AU - Yee Lim, Shyang
AU - Voon, Kelvin
AU - Young Yam, Sir
AU - Jahit, Mohammad
AU - Joon, Lee
AU - Melikidze, Besik
AU - Kazaishvili, Davit
AU - Grubelashvili, Nino
AU - Mosidze, Baadur
AU - Tomadze, Gia
AU - Megreladze, Avto
AU - Oprita, Ruxandra
AU - Pestroiu Calescu, Dorina
AU - Chioncel, Camelia
AU - Ragea, Andrei
AU - Mateescu, Bogdan
AU - Busuioc, Bogdan
AU - Voiosu, Andrei
AU - Cotirlet, Adrian
AU - Pintilie, Iulia
AU - Jinga, Mariana
AU - Balaban, Daniel
AU - Tanău, Marcel
AU - Negreanu, Lucian
AU - Bataga, Simona
AU - Priya, Khushboo
AU - Baral, Shankar
AU - Anuj, K. C.A.
AU - Sah, Vijay
AU - Yadav, Vijay
AU - Abdo, Abdelmounem
AU - Ahmed, Dalia
AU - Al Anazi, Marzouqah
AU - Al Balkhi, Areej
AU - Álvarez Gregori, Joaquín
AU - Fornieles Pérez, Helio
AU - Beqiri, Arben
N1 - Publisher Copyright: © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
PY - 2020/6/20
Y1 - 2020/6/20
N2 - Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial. Funding: UK National Institute for Health Research Health Technology Assessment Programme.
AB - Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial. Funding: UK National Institute for Health Research Health Technology Assessment Programme.
UR - https://www.scopus.com/pages/publications/85086577224
U2 - 10.1016/S0140-6736(20)30848-5
DO - 10.1016/S0140-6736(20)30848-5
M3 - Article
C2 - 32563378
AN - SCOPUS:85086577224
SN - 0140-6736
VL - 395
SP - 1927
EP - 1936
JO - The Lancet
JF - The Lancet
IS - 10241
ER -