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A drug called tranexamic acid is used to control severe bleeding caused by injury or childbirth. Some doctors had also started using it to treat patients with severe gastrointestinal (GI) bleeding, which is a common medical emergency. Evidence from small trials had suggested it could reduce deaths.

The HALT-IT (Haemorrhage alleviation with tranexamic acid-Intestinal system) trial is the largest ever to investigate the safety and effectiveness of the drug for treating patients with severe GI bleeding. It included more than 12,000 patients, with half receiving tranexamic acid and the others receiving a dummy drug (placebo).

The results showed that tranexamic acid does not improve outcomes but increases side effects for this group of patients.

This study shows that a treatment that is proven to work for certain types of severe bleeding doesn’t necessarily work for all causes. It also highlights the importance of large, randomised clinical trials for assessing the safety and effectiveness of a medicine.

What’s the issue?

Gastrointestinal (GI) bleeding is a common medical emergency that causes hundreds of thousands of deaths worldwide. In the UK, at least 50,000 people are admitted into hospital every year due to severe bleeding from the upper GI tract. The major causes are stomach ulcers, dilated veins in the food pipe, or cancer.

Around one in ten people with severe upper GI bleeding will die.  People whose bleeding is initially controlled but starts again a short while later are at particularly high risk. Treatments include blood transfusion and emergency endoscopy or surgery to locate and tie off the bleeding vessels. Drugs might also be used to reduce stomach acid or the pressure in internal veins.

Tranexamic acid is a medicine that reduces bleeding in surgery and reduces death due to bleeding after trauma and childbirth. It works by reducing the breakdown of blood clots.

Only a few small trials have looked at the safety and effectiveness of tranexamic acid for patients with severe GI bleeding. These suggested that it might help reduce deaths by up to 40%, but the evidence was not conclusive. A large trial was needed to find out whether tranexamic acid was beneficial for patients with severe GI bleeding.

What’s new?

Between 2013 and 2019, the HALT-IT trial involved more than 12,000 patients admitted into hospital with severe GI bleeding, recruited from 164 hospitals across 15 countries.

Patients were randomly assigned into two groups. Half received tranexamic acid while the others received a placebo, in addition to standard treatments. Patients, caregivers, and those assessing outcomes were unaware of which drug each patient had received.

At the end of the study, the researchers looked for differences in outcomes between the two groups. They found that tranexamic acid does not reduce deaths from GI bleeding but increases the risk of thromboembolic events (clots in the veins of the legs that can move to the lungs). There were also more seizures with tranexamic acid. There was no difference between the groups in the risk of a bleed occurring again a short while later.

Why is this important?

HALT-IT is the largest ever randomised controlled trial of tranexamic acid for patients with severe GI bleeding. The results provide no evidence that tranexamic acid improves outcomes and may increase side effects.

Some doctors had felt that the drug was too effective to withhold for people with severe GI bleeding. But this study demonstrates that the safety and effectiveness of the drug might vary according to the site and cause of bleeding.

What’s next?

Further research is now needed to understand more about the biological mechanisms underlying severe GI bleeding. This could generate new leads for the development of effective new treatments for patients with this life-threatening symptom.

You may be interested to read

The full paper: The 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;395:1927-1936

Ronellenfitsch U. In people with upper gastrointestinal bleeding, what are the effects of tranexamic acid? Cochrane Clinical Answers 2019. DOI: 10.1002/cca.1128

Bennett C, and others. Tranexamic acid for upper gastrointestinal bleeding. Cochrane Database Syst Rev 2014;11

The CRASH-2 collaborators. The importance of early tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. The Lancet 2011;377:1096–1101.

The NIHR HTA report on the HALT-IT trial: Roberts I, and others. A high-dose 24-hour tranexamic acid infusion for the treatment of significant gastrointestinal bleeding: HALT-IT RCT. Health Technology Assessment 2021;25:58


Funding: This research was funded by the NIHR Health Technology Assessment Programme.

Conflicts of Interest: The study authors declare no conflicts of interest.

Disclaimer: NIHR Alerts are not a substitute for professional medical advice. They provide information about research which is funded or supported by the NIHR. Please note that views expressed in NIHR Alerts are those of the author(s) and reviewer(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

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Study author

People had already made up their minds before the results of the trial. There was a groundswell of opinion that tranexamic acid would work for these patients. Although I was disappointed that we did not find a beneficial effect, it shows that big trials are the best way to assess the safety and effectiveness of a medicine. Combining the results from a series of smaller trials can generate hypotheses, but they’re not good enough evidence on which to base clinical practice.Ian Roberts, Professor in Epidemiology, London School of Hygiene & Tropical Medicine

Specialist Clinician

This is a surprising result. Although tranexamic acid is not part of gastrointestinal bleed guidelines, it is often prescribed for these patients as it is perceived to be safe and, up to now, potentially beneficial. The results of this well-conducted study will change this practice since it has now been shown that the drug is not beneficial and potentially harmful.Simon Anderson, Consultant Physician and Gastroenterologist, Guy’s and St Thomas’ NHS Foundation Trust
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