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Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

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posted on 28.07.2020, 09:25 by Ian Roberts, Haleema Shakur-Still, Adefemi Afolabi, Adegboyega Akere, Monica Arribas, Amy Brenner, Rizwana Chaudhri, Ian Gilmore, Kenneth Halligan, Irshad Hussain, Vipul Jairath, Kiran Javaid, Aasia Kayani, Ton Lisman, Raoul Mansukhani, Muttiullah Mutti, Muhammad Arif Nadeem, Richard Pollok, Jonathan Simmons, Majid Soomro, Simon Stanworth, Andrew Veitch, Christopher Hawkey, Jack Cuzick, David Henry, Chris Metcalfe, Richard Gray, Alan Barkun, Suresh David, Philip Devereaux, Tony Brady, Timothy Coats, Phil Edwards, Katharine Ker, Daniela Manno, Emma Austin, Kiran Bal, Eni Balogun, Collette Barrow, Danielle Beaumont, Myriam Benyahia, Imogen Brooks, Madeleine Cargill, Laura Carrington, Lauren Frimley, Amber Geer, Daniel Gilbert, Catherine Gilliam, Julio Gil Onandia, Nayia Golfi, Daniel Hetherington, Courtenay Howe, Carolyn Hughes, David I'anson, Rob Jackson, Miland Joshi, Sneha Kansagra, Taemi Kawahara, Sergey Kostrov, Hakim Miah, Bernard Ndungu, Kelly Needham, Aroudra Outtandy, Daniel Pearson, Tracey Pepple, Danielle Prowse, Nigel Quashi, Anna Quinn, Maria Ramos, Laura Ranopa, Mia Reid, Chris Roukas, Chelci Squires, Jemma Tanner, Andrew Thayne, Ruhama Uddin, Bukola Fawole, Folasade Adenike Bello, Oladapo Olayemi, Olujide Okunade, Olusade Adetayo, Hussein Khamis, Mohammad Shukri Bin Jahit, Tamar Gogichaishvili, Radu Bogdan Mateescu, Ajay Adhikaree, Abdelmounem Eltayeib Abdo, Mohammad Zaher, Conor Deasy, Joaquin Alvarez Gregori, Bobby Wellsh, Luke Lawton, Raghavendra Kamath, Adrian Barry, Racquel Carpio, Kay Finney, Holly Maguire, Martin James, Frank Coffey, Chris Gough, Lisa Sawers, Aye-Aye Thi, Claire Burnett, Nicola Jacques, Victoria Murray, Heather Jarman, Christine Lambe, Sarah Rounding, Simon Tucker, Romaih Al-Idari, Samuel Guest, Emma Stoddard, David Yeo, Colin Bergin, Elaine Hardy, Joanne Thunder, Paul Jhalli, Edward Hartley, Catherine Jarvis, Carly Swann, Matthew Reed, Bernadette Gallagher, Julia Grahamslaw, Rachel O'Brien, Timothy Harris, Geoffrey Bellhouse, Olivia Boulton, Imogen Skene, Adrian Stanley, Janet Johnstone, Donogh Maguire, Susan Thornton, Matthew Banks, Georgia Bercades, Daniel Marks, Jung Ryu, Claire Dowty, Jason Pott, James East, Adam Bailey, Sally Beer, Sian Davies, Andrew Appelboam, Daisy Mackle, Jennifer Small, Christiane Vorwerk, Rachel Atkins, Isobel Bradbury, Catriona Bryceland, Lisa McClelland, Martin Thomas, Kate Clayton, Angiy Michael, Stephen Haig, Saif Al-Nahhas, Tim Godfrey, Philip Boger, Rachel Comer, Barbara Watkins, Ola Afolabi, Shazad Afzal, Amanda Cowton, Simon Everett, Ruth Fazakerley, Felicia Onoviran, Jonathon Snook, Jackie Berry, Diane Simpson, Jeff Keep, Hannah Cotton, Sinead Helyar, Matthew Rutter, Tracey Johnston, Laura O'Rourke, Louisa Chan, Joanna Tambellini, Dawn Trodd, James Shutt, Sarah Moreton, Abby Oglesby, Adrian Boyle, Nicola Haeger, Susie Hardwick, Jason Kendall, Beverley Faulkner, Ruth Worner, Sarah Hearnshaw, Mary Doona, Maria Price, Laura Hunter, Maggie Bell, Vania Loureiro, Anthony Kehoe, Alison Jefferey, Rosalyn Squire, David Hartin, Stephanie Bell, Alexandra Newman, James Gagg, Jayne Foot, Sue Wakeford, Gabrielle May, Thomas Bartram, Paul Cumpstay, Lucy Parker, Rita Das, Sheik Pahary, Gavin Wright, Georgina Butt, Natasha Christmas, Sarah Wilson, Mohammed Ashfaq, Louise Chandler, Carrie Demetriou, Philip Kaye, Simon Carley, Andrew Brown, Lucy Jones, Amanda Whileman, John Greenaway, Julie Tregonning, Avril Kuhrt, Steve Goodacre, John Jones, Charlotte Owen, Anu Mitra, Abby Harper-Payne, Nigel Trudgill, Anne Hayes, Faheem Butt, Gayle Clifford, Andrew Kinnon, Susan Fowler, Kris Pillay, Shweta Gidwani, Alistair McNair, Omer Omer, Tanya de Weymarn, Adnan Amin, Jane Martin, Nick Mathieu, Simon Barnes, James Turvill, Helen Sweeting, Morten Draegebo, Marion McNaught, Mandy Grocutt, Jordi Margalef, Julian Humphrey, Richard Jackson, Fionn Bellis, Jane Hunt, Alastair Stevenson, Nicholas Watson, Steven Barden, Stuart Paterson, Chris Macdonald, David Hobday, Olu Orugun, Andrew Allison, Tristan Dyer, Samuel McBride, Wojciech Sawicki, Ben Rayner, Lynsey Flowerdew, Jamie Barbour, Jason Klein, Stephen Hood, Nicola Palmer, Jacob de Wolff, Achuth Shenoy, Peter Swallow, Rajaventhan Srirajaskanthan, Hamza Arshad, Naeem Aslam, Anam Bangash, Muhammad Qamar, Haroon Zahoor, Saba Arshad, Quratul ain Ghalib, Tehseen Hameed, Tayyaba Saif, Wajahat Shafi, Abid Ali, Shehroze Khan, Muhammad Muaaz, Ahmad Taj, Aamir Ghafoor, Aamir Afridi, Mansoor Ahmad, Mujahid Aslam, Sandeep Kumar, Mohsin Ali, Ubedullah Bughio, Adil Chang, Sana Shaikh, Syed Ahmad, Zeeshan Ali, Marium Waqar, Aiman Mushir, Sadaf Sattar, Saifullah Goraya, Sharmeen Aslam, Nighat Fatima, Saadia Noreen, Sheraz Saleem, Fazal Rahman, Nadeem Iqbal, Mohammad Khalid, Umar Riaz, Muhammad Umar, Tayyab Akhter, Javaria Khan, Noureen Misbah, Muhammad Afzal, Mobeen Kayani, Syed Shah, Shahida Tarar, Sherbat Khan, Yasir Iqbal, Essa Khan, Maqbool Reki, Tanveer Hussain, Shafqat Iqbal, Muhammad Khurram, Muhammad Shafi, Abrar Shaikh, Aijaz Ahmed, Ameet Kumar, Pinkey Sachdev, Khalid Mahmood Nasir, Zafar Iqbal Chaudhry, Muhammad Zubair, Ghias Tayyab, Junaid Mushtaq, Muhammad Nasir, Amir Khan, Amjad Ali, Sajjad Ali, Wasim Uddin, Sohaib Ahmed, Tazaeen Kazmi, Saleh Channa, Adeeqa Aman, Mouzam Shaikh, Tahir Rizvi, Amjad Hussain, Haider Zaigham Baqai, Zakawat Rasheed, Abdus Khan, Adeela Irfan, Aamir Husain, Asifa Aslam, Khalid Yahya, Salman Azhar, Mansoor Ul Haq, Adeel Afzal, Muhammad Imran, Iram Saeed, Aasim Yusuf, Mariam Hassan, Mumtaz Marwat, Muhammad Ishfaq, Tahir Bashir, Santosh Kumar, Sajjad Yaqoob, Abdul Wahid, Tinuola Fakoya, Temitope Oke, Edries Tejan, Oluwole Olaomi, Olawale Badejo, Okafor Nnaemaka, Nancy Ukwu, Olukayode Arowolo, Adewale Aderounmu, Funmilola Wuraola, Rose Ugiagbe, Alexander Atiri, Enadeghe Eghaghe, Adeleke Adekoya, Adedayo Oluyomi Tade, Olatunji Shonoiki, Samuel Olatoke, Toafiq Raji, Christopher Ekwunife, Chigozirim Onyekpere, Adamu Ahmed, Daniyan Muhammad, Emuobor Odeghe, Olufunmilayo Lesi, Azeberoje Osueni, Adamu Samaila, Aminu Nahuche, Akande Ajayi, Andrew Dongo, Uchenna Ijoma, Ademola Tolulope Adebanjo, Rufina Igetei, Monday Yilkudi, Kehinde Osisanya, Edith Nonyelum Okeke, Oguamanam Okezie Enwere, Serag Esmat, Omar Ashoush, Mazen Naga, Fady Nagy, Mostafa Saiid, Ahmed Shaker, Ashraf Helmy, Saafan Saafan, Mohammed Abdel Monem, Jiffre Din, Khairul Azis, Muhyuddin Brukan, Sanjay Singh, Andee Zakaria, Shaik Farid, Nizam Hashim, Masykurin Mafauzy, Wan Najmi, Nil Amri, Xin Yi, Mohammad Hisyam, Elaine Ng, Zuhrirahimi Ramli, Shyang Yee Lim, Kelvin Voon, Sir Young Yam, Mohammad Jahit, Lee Joon, Besik Melikidze, Davit Kazaishvili, Nino Grubelashvili, Baadur Mosidze, Gia Tomadze, Avto Megreladze, Ruxandra Oprita, Dorina Pestroiu Calescu, Camelia Chioncel, Andrei Ragea, Bogdan Mateescu, Bogdan Busuioc, Andrei Voiosu, Adrian Cotirlet, Iulia Pintilie, Mariana Jinga, Daniel Balaban, Marcel Tanău, Lucian Negreanu, Simona Bataga, Khushboo Priya, Shankar Baral, Anuj K.C., Vijay Sah, Vijay Yadav, Abdelmounem Abdo, Dalia Ahmed, Marzouqah Al Anazi, Areej Al Balkhi, Joaquín Álvarez Gregori, Helio Fornieles Pérez, Arben Beqiri

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.

History

Citation

The HALT-IT Trial Collaborators, Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial, Lancet 2020; 395: 1927–36

Version

VoR (Version of Record)

Published in

The Lancet

Volume

395

Issue

10241

Pagination

1927 - 1936

Publisher

Elsevier: Lancet

issn

0140-6736

eissn

1474-547X

Copyright date

2020

Available date

28/07/2020

Language

en

Publisher version

https://www.sciencedirect.com/science/article/abs/pii/S0140673620308485

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