EBQ:Halt It Trial

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incomplete Journal Club Article
Roberts I, Shakur-Still H, Afolabi A, et al.. "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(10241):1927-1936.
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Clinical Question

Does high-dose IV tranexamic acid reduce death due to bleeding within five days in adult patients with acute gastrointestinal bleeding compared to placebo?


Tranexamic acid confers no benefit on 5-day mortality due to bleeding in adult patients with acute GI bleed.

Major Points

Tranexamic acid (TXA) is a synthetic lysine derivative that decreases fibrinolysis by inhibiting the conversion of plasminogen to plasmin. It has been used broadly in trauma patients with hemodynamically significant bleeding and appears to confer a mortality benefit in this population[1]. A prior systematic review of TXA for use in acute gastrointestinal bleeding suggested a mortality benefit, although the review was based on a series of small studies prone to bias[2].

HALT-IT is the first large, pragmatic, international, double-blind RCT to systematically evaluate the use of TXA in acute undifferentiated GI bleed. In this study, patients that received TXA 1g IV loading dose followed by a 3g infusion over 24 hours had the same mortality rate from bleeding at five days as patients receiving a matching normal saline placebo (222 [3.7%] intervention group vs 226 [3.8%] placebo, RR 0.99). All-cause mortality at 28 days was also no different between groups. There was a suggestion of increased venous thromboembolic events in the TXA group (48 [0.8%] vs 26 [0.4%], RR 1.85 [CI 1.15-2.98]).

Study Design

Large, pragmatic, multicenter international placebo-controlled RCT, conducted at 164 hospitals in 15 countries

  • 12,009 patients enrolled with acute GI bleeding


Patient Demographics

  • Patients older (mean age 58), male (65%), and mostly upper GI bleeds (90%)
  • Mean time to randomization from onset of bleeding 22h
  • Most patients (57%) did not display signs of shock on initial presentation

Inclusion Criteria

  • Adult patients with acute gastrointestinal bleeding
  • Clinician defined bleeding as significant, meaning possibility of death from bleeding
    • Age of inclusion either 16 or 18 depending on definition of "adult" in home country
  • Clinician had to be "uncertain" whether or not to use TXA

Exclusion Criteria

  • Clinician-determined clear indication for TXA
  • Clinician-determined clear contraindication for TXA


  • TXA 1g IV over 10 minloading dose followed by a 3g infusion in NS over 24 hours


Primary Outcome

  • Death from bleeding at 5 days
    • No difference between TXA (222, 3.7%)and placebo (226, 3.8%)

Secondary Outcomes

  • All-cause mortality at 28 days
    • Originally was the primary outcome, replaced by the above (see discussion)
    • No difference between TXA (9.5%) and placebo (9.2%), RR 1·03, 95% CI 0·92– 1.16
  • No difference in rebleeding, need for endoscopy/surgery, transfusion requirement, or mortality from other subgroups (i.e. infection, organ failure, etc)
  • Thromboembolic events
    • Any: 1.4% in TXA group vs 1.2% in placebo (RR 1.20, 95% CI 0.88-1.64)
    • Venous (DVT and PE): 0.8% in TXA group vs 0.4% in placebo (RR 1.85, 95% CI 1.15-2.98)
  • Seizures
    • 0.6% in TXA group vs 0.4% in placebo (RR 1.73, 95% CI 1.03-2.93

Subgroup analysis

4 preplanned subgroups within the primary outcome:

  • Time from onset of bleeding, greater or less than 3h
  • Site of bleed, upper or lower
  • Varices and comorbid liver disease vs other causes of bleeding
  • Rockall score

TXA showed no benefit in any subgroup.

Criticisms & Further Discussion

  • Previous positive studies of TXA on GI bleeds have been small or observational and subject to bias
  • This large RCT is well-designed, pragmatic, and answers a clinically relevant question
  • The study authors changed the original primary outcome from all-cause 28-day mortality to death due to bleeding at 5 days
    • During an interim analysis authors noted that >50% of deaths were from non-hemorrhagic causes
    • New primary outcome is disease-specific and at the judgment of the clinician
  • Patients for whom TXA was thought to be "clearly indicated" were excluded from the trial
    • Some sicker patients who could have benefited from TXA may have been excluded
  • Time to randomization was long (22 hours on average); CRASH-2 signaled that earlier administration of TXA is better
    • However, GI bleed patients tend to present roughly in the timeframe represented in the trial

External Links

See Also


The UK National Institute for Health Research Health Technology Assessment Programme


  1. Roberts I et al. 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. The Lancet. 2020; 395(10241):1927-1936
  2. Bennett C, Klingenberg SL, Langholz E, Gluud LL. Tranexamic acid for upper gastrointestinal bleeding. The Cochrane database of systematic reviews. 2014