A high-dose 24-hour tranexamic acid infusion for the treatment of significant gastrointestinal bleeding: HALT-IT RCT

• Published in: Health technology assessment (Winchester, England) England), 2021-10, Vol.25 (58), p.1-86
• Main Authors: Roberts, Ian, Shakur-Still, Haleema, Afolabi, Adefemi, Akere, Adegboyega, Arribas, Monica, Austin, Emma, Bal, Kiran, Bazeer, Nuha, Beaumont, Danielle, Brenner, Amy, Carrington, Laura, Chaudhri, Rizwana, Coats, Timothy, Gilmore, Ian, Halligan, Kenneth, Hussain, Irshad, Jairath, Vipul, Javaid, Kiran, Kayani, Aasia, Lisman, Ton, Mansukhani, Raoul, Miners, Alec, Mutti, Muttiullah, Nadeem, Muhammad Arif, Pollok, Richard, Prowse, Danielle, Simmons, Jonathan, Stanworth, Simon, Veitch, Andrew, Williams, Jack
• Format: Article
• Language: English
• Subjects: blood loss; blood transfusion; cost-benefit analysis; gastrointestinal haemorrhage; pulmonary embolism; stroke; tranexamic acid; venous thrombosis
• ISSN: 1366-5278; 2046-4924
• DOI: 10.3310/hta25580

BACKGROUNDTranexamic acid reduces blood loss in surgery and the risk of death in trauma patients. Meta-analyses of small trials suggest that tranexamic acid decreases the number of deaths from gastrointestinal bleeding, but these meta-analyses are prone to selection bias. OBJECTIVEThe trial provides reliable evidence of the effect of tranexamic acid on mortality, rebleeding and complications in significant acute gastrointestinal bleeding. DESIGNA multicentre, randomised, placebo-controlled trial and economic analysis. Patients were assigned by selecting one treatment pack from a box of eight, which were identical apart from the pack number. Patients, caregivers and outcome assessors were masked to allocation. The main analyses were by intention to treat. SETTINGThe setting was 164 hospitals in 15 countries, co-ordinated from the London School of Hygiene & Tropical Medicine. PARTICIPANTSAdults with significant upper or lower gastrointestinal bleeding (n = 12,009) were eligible if the responsible clinician was substantially uncertain about whether or not to use tranexamic acid. The clinical diagnosis of significant bleeding implied a risk of bleeding to death, including hypotension, tachycardia or signs of shock, or urgent transfusion, endoscopy or surgery. INTERVENTIONTranexamic acid (a 1-g loading dose over 10 minutes, then a 3-g maintenance dose over 24 hours) or matching placebo. MAIN OUTCOME MEASURESThe primary outcome was death due to bleeding within 5 days of randomisation. Secondary outcomes were all-cause and cause-specific mortality; rebleeding; need for endoscopy, surgery or radiological intervention; blood product transfusion; complications; disability; and days spent in intensive care or a high-dependency unit. RESULTSA total of 12,009 patients were allocated to receive tranexamic acid (n = 5994, 49.9%) or the matching placebo (n = 6015, 50.1%), of whom 11,952 (99.5%) received the first dose. Death due to bleeding within 5 days of randomisation occurred in 222 (3.7%) patients in the tranexamic acid group and in 226 (3.8%) patients in the placebo group (risk ratio 0.99, 95% confidence interval 0.82 to 1.18). Thromboembolic events occurred in 86 (1.4%) patients in the tranexamic acid group and 72 (1.2%) patients in the placebo group (risk ratio 1.20, 95% confidence interval 0.88 to 1.64). The risk of arterial thromboembolic events (myocardial infarction or stroke) was similar in both groups (0.7% in the tranexamic acid group vs. 0.8% in the placeb