HALT-IT

What was the research question?

Does a high-dose 24-hour infusion of tranexamic acid reduce death and thromboembolic events in patients with acute gastrointestinal bleeding when compared to a placebo?

How did they do it?

• An international, randomized, double-blind, placebo-controlled study conducted in 164 hospitals in 15 countries.

• Adult patients with upper or lower gastrointestinal bleeding with risk of death.

• Patients were randomized to receive either a loading dose of 1 g tranexamic acid in 100 mL infusion bag of 0·9% sodium chloride over 10 minutes, 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 (5956 patients), or placebo with sodium chloride 0·9% (5981 patients).

• The study's primary outcome was death from bleeding within 5 days of randomization, with secondary outcomes including death from bleeding within 24 hours and 28 days of randomization, all-cause and cause-specific mortality at 28 days, rebleeding within 24 hours, 5 days, and 28 days of randomization, surgery or radiological intervention, blood product transfusion, thromboembolic events, seizures, other complications, and days in an intensive care unit.

What did they find?

• Death due to bleeding within 5 days of randomization occurred in 222 (3·7%) of 5956 patients in the tranexamic acid group and in 226 (3·8%) of 5981 patients in the placebo group (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; RR 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).

• Seizures occurred in 38 patients on tranexamic acid and 22 on placebo (0·6% vs 0·4%; 1·73, 1·03–2·93).

• Death due to bleeding within 24 hours and 28 days of randomization, as well as all-cause mortality within 28 days, were similar in both groups.

• The proportion of patients with rebleeding, surgery, radiological intervention, and blood product transfusion was also similar in both groups.

What are the limitations?

• The inability to evaluate the efficacy of tranexamic acid for particular patient subgroups and the exclusion of individuals with high-risk stigmata.

What does it mean?

• The study suggests that a high-dose 24-hour infusion of tranexamic acid does not reduce death within 5 days of randomization in patients with acute gastrointestinal bleeding.

• It cannot, however, rule out minor therapy effects. Individual patient data meta-analyses should be performed to determine the efficacy and safety of tranexamic acid based on the site and source of bleeding.