HALT-IT: TXA for Acute GI Bleeding

Conclusion: TXA provides no mortality benefit to patients with GI bleeding and may cause harm with increased rates of venous thromboembolic events

• The HALT-IT trial was an international, randomised, double-blind, placebo-controlled trial from 164 hospitals in 15 countries, enrolling adults with significant GI bleeding 
  • The diagnosis of significant bleeding was clinical and significant was defined as a risk of bleeding to death and included patients with hypotension, tachycardia, or signs of shock, or those likely to need transfusion or urgent endoscopy or surgery
• Intervention: Patients were randomised to 1 g of TXA infused over 10 minutes followed by an infusion of 125 mg/hour for 24 hours or a normal saline placebo
• The primary outcome was death due to bleeding within 5 days of randomisation
  • Secondary outcomes included:
    • Death due to bleeding within 24 h and within 28 days of randomisation
    • All ­cause and cause-­specific mortality at 28 days,
    • Re-bleeding within 24 h, within 5 days, and within 28 days of randomisation
    • Surgery or radiological intervention
    • Blood product transfusion
    • Thromboembolic events (deep vein thrombosis, pulmonary embolism, stroke, and myocardial infarction),
    • Seizures and other com­plications (including other significant cardiac event, sepsis, pneumonia, respiratory failure, renal failure, liver failure)
    • Days in an intensive care unit
    • Functional status
• A total of 12,009 patients were enrolled; 64% were male, and the mean age was 58 years
  • 9% were taking anticoagulants
  • 89% were suspected to have upper-GI bleeding
  • 43% had signs of shock
• There was no significant difference in the primary outcome of death due to bleeding within 5 days of randomisation between the groups: 222 (3.7%) for TXA vs 226 (3.8%) for placebo; RR 0.99 (95% CI 0.82-1.18)
  • Though the choice of death at 5 days post randomisation had the potential to miss patients achieving that outcome after the 5 day mark, there was no evidence of treatment effect for death from any cause at 28 days, so the choice of endpoint does not appear to influence the interpretation of the results
• They found a difference in only 1 secondary outcome:
  • Higher incidence of venous thromboembolism events in the TXA group (0.8%) vs the placebo group (0.4) (RR 1.85, NNH = 250)
• Strengths:
  • Very large multinational study increases external validity
  • Well matched cohorts with minimal loss to follow up and low rate of protocol violations
• Limitations:
  • Key limitation – Time to TXA administration may represent a significant cofounder – the mean time until intervention was 21.4 hours in the TXA group and 22.5 hours in the placebo group
    • CRASH-trial data has demonstrated that TXA treatment effect is demonstrated when administered within 3 hrs
  • This study looked at all comers with GI bleeding which potentially miss subgroups where there my be true benefit (e.g. UGI vs LGI bleed)

Full article: https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(20)30848-5.pdf

Reference: 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 Jun 20;395(10241):1927-1936.