Title: HALT-IT trial (Haemorrhage Alleviation with Tranexamic acid–Intestinal System), a large randomised placebo controlled trial among patients with acute gastrointestinal haemorrhage of the effects of tranexamic acid on death and transfusion requirement
Funder: Department of Health and Social Care

Abstract: The HALT-IT trial is a randomised double-blind placebo controlled trial to evaluate the safety and cost-effectiveness of giving tranexamic acid (TXA) to adults with acute severe gastrointestinal (GI) bleeding. TXA is widely used to treat menorrhagia and is used in surgery to reduce bleeding. In 2010, the CRASH-2 trial showed that TXA reduces mortality in bleeding trauma patients. TXA reduces death due to bleeding (RR=0.85, 95% CI 0.76 to 0.96; p=0.008) and all cause mortality (RR=0.91, 95% CI 0.85 to 0.97; p=0.004), with no apparent increase in vascular occlusive events. TXA could also reduce mortality in GI bleeding. When combined, previous trials of TXA in GI bleeding show a mortality reduction (RR=0.67, 95% CI 0.47 to 0.95; p=0.02), although the quality of the trials is poor. Most previous trials were conducted in the 1970s and 80s before the use of endoscopy and proton pump inhibitors (PPI). The poor quality of the evidence and concerns about its applicability probably explain why few patients with GI bleeding are treated with TXA. The HALT-IT trial will randomly allocate 8,000 patients with GI bleeding to receive a loading dose of 1 g of TXA infused over 10 minutes, followed by an intravenous infusion of 3 g over 24 hours, or matching placebo. TXA or placebo will be administered in addition to the normal medical or surgical treatment for acute severe GI bleeding. We will assess the effect of TXA on all-cause mortality, side effects and health-related quality-of-life. The trial design and outcomes were decided upon following discussion with user groups. The trial is coordinated by a CTU with experience in clinical trials in emergency situations. We work with an established international network of doctors who have a proven track record of recruitment to emergency care trials. To ensure that the results of the trial apply to patients in the NHS, there will be a strong focus on UK recruitment which will contribute about 2,000 patients. The clinical leadership provided by the applicants Professor Ian Gilmore (president of British Society of Gastroenterology) and Dr Andrew Veitch (Chair of the UK Endoscopy Research Network) and the support of the relevant CLRN will help with this.

Lay abstract: About 50,000 people each year end up in British hospitals because of really bad gut bleeding. About 5,000 patients of them die. Gut bleeding is usually caused by stomach ulcers. Liver damage from alcohol is another cause and with more and more people hitting the bottle in the UK, this is a growing problem. A very big clinical trial in bleeding accident victims found that a cheap drug called tranexamic acid reduces the chances of bleeding to death without any increase in side effects. If this drug also works in severe gut bleeding, this would be important to know because it could save lives at very low cost. Researchers have already done some studies to see if tranexamic acid helps people with gut bleeding. When all the research is gathered together, the results look reasonably encouraging. However, the research is not of very good quality and was done about thirty years ago and might be out of date now. Very few NHS doctors give tranexamic acid for gut bleeding but if a new clinical trial showed it worked this could change really quickly. We will find out if tranexamic acid saves lives and improves quality of life for patients with bad gut bleeding. We plan to study 8,000 patients with severe gut bleeding from Britain (about 2,000 patients) and other countries. We will give half of them tranexamic acid and the other half a dummy medicine called a placebo. To make sure that the two groups are the same apart from tranexamic acid, we will decide who gets tranexamic acid and who gets placebo using the modern equivalent of the toss of a coin (this is called randomisation). Everyone will of course get all the treatments that doctors usually give for this condition. At the end of the trial we will then see if giving tranexamic acid on top of all the usual treatments improves survival and other patient outcomes. In emergency situations like this it is difficult for patients to give written informed consent to be in a trial because they are often too sick. We will therefore ask the ethics committee for permission to put patients into the trial without written consent, and we will explain to patients later what happened to them and how the information from the trial will be used. We have asked the opinions of members of the public about this and they agree that this is the only way we can do good research on life threatening emergency problems. The study will be carried out by a team of researchers with lots of experience in doing research on emergency conditions. In fact, it will be the same team that did the successful study of tranexamic acid in accident victims. The trial will cost around three million pounds but if it shows (as we hope it will) that tranexamic acid works, we will have a very cheap way of helping people with this nasty condition. In fact, it could end up being one of the best buys in the whole NHS. It might even save money if it reduces the need for expensive blood transfusions or operations.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: ORAL AND GASTROINTESTINAL