Journal Article

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

Afolabi, Adefemi, Murray, Victoria, Jinga, Mariana, Imran, Muhammad, Moreton, Sarah, Arowolo, Olukayode, Fakoya, Tinuola, Gil Onandia, Julio, Hobday, David, Tanner, Jemma, Bell, Maggie, Golfi, Nayia, Grubelashvili, Nino, Hawkey, Christopher, Joon, Lee, Thayne, Andrew, Pearson, Daniel, Mutti, Muttiullah, Aslam, Naeem, Ukwu, Nancy, Dyer, Tristan, Onoviran, Felicia, Okunade, Olujide, Bartram, Thomas, Reki, Maqbool, Johnstone, Janet, Draegebo, Morten, Al-Idari, Romaih, Cuzick, Jack, Harris, Timothy, Margalef, Jordi, Hussain, Tanveer, Jarman, Heather, Ali, Abid, Kaye, Philip, Raji, Toafiq, Tade, Adedayo Oluyomi, Tarar, Shahida, Thomas, Martin, Butt, Georgina, Godfrey, Tim, Wuraola, Funmilola, Noreen, Saadia, Lambe, Christine, Wilson, Sarah, Ali, Mohsin, Hetherington, Daniel, Thi, Aye-Aye, Kamath, Raghavendra, Mafauzy, Masykurin, Khan, Essa, ain Ghalib, Quratul, Chang, Adil, Abdel Monem, Mohammed, Yeo, David, Pestroiu Calescu, Dorina, Guest, Samuel, Kazaishvili, Davit, Saleem, Sheraz, Javaid, Kiran, Afzal, Shazad, Brukan, Muhyuddin, Baral, Shankar, Helyar, Sinead, Nnaemaka, Okafor, Ramli, Zuhrirahimi, Kendall, Jason, Atiri

2020

Overview

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. 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. 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). 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. UK National Institute for Health Research Health Technology Assessment Programme.

• Publisher: Elsevier Ltd,Elsevier B.V,Elsevier Limited,Elsevier
• Subject: Acids / Acute Disease / Adult / Aged / Analysis / Antifibrinolytic agents / Antifibrinolytic Agents - administration & dosage / Antifibrinolytic Agents - adverse effects / Antifibrinolytic Agents - therapeutic use / Bleeding / Blood products / Care and treatment / Case-Control Studies / Cerebral infarction / Chloride / Chlorides / Clinical trials / Data collection / Death / Dichloropropane / Dosage and administration / Double-Blind Method / Double-blind studies / Drug therapy / Embolism / Fatalities / Female / Gastrointestinal bleeding / Gastrointestinal Hemorrhage - drug therapy / Gastrointestinal Hemorrhage - mortality / Gastrointestinal Hemorrhage - prevention & control / Health risk assessment / Humans / Injections, Intravenous / Intravenous administration / Male / Medical research / Medicine, Experimental / Middle Aged / Mortality / Myocardial infarction / Myocardial Infarction - epidemiology / Odds Ratio / Outcome Assessment, Health Care / Patients / Placebos - administration & dosage / Predictive Value of Tests / Pulmonary embolism / Pulmonary Embolism - epidemiology / Randomization / Sodium chloride / Stroke - epidemiology / Surgery / Systematic review / Technology assessment / Thromboembolism / Thromboembolism - chemically induced / Thromboembolism - epidemiology / Thrombosis / Tranexamic acid / Tranexamic Acid - administration & dosage / Tranexamic Acid - adverse effects / Tranexamic Acid - therapeutic use / Trauma / Venous Thrombosis - epidemiology