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

Abstract

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.

The Immunologic Effect of Early Intravenous Two and Four Gram Bolus Dosing of Tranexamic Acid Compared to Placebo in Patients With Severe Traumatic Bleeding (TAMPITI): A Randomized, Double-Blind, Placebo-Controlled, Single-Center Trial

“…In contrast to our study, these trials did not use active Duplex screening for TE, thereby potentially underreporting TE events. However, our results are consistent with the HALT-IT study, an RCT on TXA use in 12,000 adults with gastrointestinal bleeding that reported an increase in TE when TXA is used in this population (59).…”

Is There a Role for Tranexamic Acid in Upper GI Bleeding? A Systematic Review and Meta-Analysis

“…It should also be noted that the recent HALT-IT trial was included in this study even though it assessed the effects of TXA on GI bleeding in general but not isolated to upper GI sources. The reasoning behind this was the fact that the study reported that over 89% of those included in the study were deemed to have an upper GI bleed and thus it should be translatable to our study [ 12 ]. Also, this study is the largest and most recent study of its kind assessing this question and so it was deemed appropriate to include it with the above proviso acknowledged.…”

“…The characteristics of the studies included are detailed in Table 2 . A total of 8 studies were included in this systematic review [ 12 – 19 ]. The number of patients included in the studies ranged from a low of 47 to a high of 12009.…”

Tranexamic acid for acute gastrointestinal bleeding: updated after the HALT‐IT trial

“…Twum‐Barimah et al recently addressed the importance of tranexamic acid in acute gastrointestinal bleeding in their systematic review 1 . The HALT‐IT trial reported contradictory results ‐ that is, tranexamic acid confers no additional survival benefit and is associated with increased harm 2 . Karadaş et al found no statistically significant difference in mortality between patients with gastrointestinal bleeding who received tranexamic acid or placebo 3 .…”

“…Forest plot of tranexamic acid vs placebo on mortality and overall outcome summary, including 24‐hour mortality, 72‐hour mortality, 1‐month mortality and end of follow‐up mortality. ✶ HALT‐IT trial reported 28‐day mortality, which was also included in our 1‐month mortality analysis 2 . † Two studies published in 2020 were added in addition to those included in the meta‐analysis by Erica Twum‐Barimah et al 2,3 ‡ Two studies published in 2020 and one study whose reported outcome was missed were added in addition to those included in the meta‐analysis by Erica Twum‐Barimah et al 2,3,5 § One study published in 2020 and one study whose reported outcome was missed were added in addition to those included in the meta‐analysis by Erica Twum‐Barimah et al 2,6 …”