HALT-IT - tranexamic acid for the treatment of gastrointestinal bleeding: study protocol for a randomised controlled trial

Abstract

BackgroundGastrointestinal bleeding is a common emergency that causes substantial mortality worldwide. Acute upper and lower gastrointestinal bleeding accounts for about 75,000 hospital admissions each year in the UK and causes the death of about 10% of these patients.Tranexamic acid has been shown to reduce the need for blood transfusion in surgical patients and to reduce mortality in bleeding trauma patients, with no apparent increase in thromboembolic events.A systematic review of clinical trials of upper gastrointestinal bleeding shows a reduction in the risk of death with tranexamic acid but the quality of the trials was poor and the estimates are imprecise. The trials were also too small to assess the effect of tranexamic acid on thromboembolic events.MethodsHALT-IT is a pragmatic, randomised, double-blind, placebo-controlled trial which will determine the effect of tranexamic acid on mortality, morbidity (re-bleeding, non-fatal vascular events), blood transfusion, surgical intervention, and health status in patients with acute gastrointestinal bleeding. Eight thousand adult patients who fulfil the eligibility criteria will be randomised to receive tranexamic acid or placebo.Adults with significant acute upper or lower gastrointestinal bleeding can be included if the responsible doctor is substantially uncertain as to whether or not to use tranexamic acid in that particular patient.Trial treatment consists of a loading dose of tranexamic acid (1 g by intravenous injection) or placebo (sodium chloride 0.9%) given as soon as possible after randomisation, followed by an intravenous infusion of 3 g tranexamic acid or placebo (sodium chloride 0.9%) over 24 hours.The main analyses will compare those allocated tranexamic acid with those allocated placebo, on an intention-to-treat basis. Results will be presented as effect estimates with a measure of precision (95% confidence intervals). Subgroup analyses for the primary outcome will be based on time to treatment, source of bleeding (upper versus lower), suspected variceal bleeding and severity of bleeding. A study with 8,000 patients will have over 90% power to detect a 25% reduction in mortality from 10% to 7.5%.Trial registrationCurrent Controlled Trials ISRCTN11225767 (registration date: 3 July 2012); Clinicaltrials.gov NCT01658124 (registration date: 26 July 2012).Electronic supplementary materialThe online version of this article (doi:10.1186/1745-6215-15-450) contains supplementary material, which is available to authorized users.

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

“…Bearing in mind that even a large trial such as ours would have limited power to detect a time to treatment interaction for death due to bleeding, setting the trial results in the context of the totality of the available evidence seemed to be the most sensible approach. Although there are on-going trials of tranexamic acid in life threatening bleeding, the CRASH-2 trial is the only trial to date that provides such evidence 24, 25Figure 5 shows the results of the WOMAN trial in the context of the CRASH-2 results.…”

Transfusion strategies in patients with cirrhosis

“…They recommended additional prospective, randomized, double‐blinded studies in order to determine the effects of TXA in the setting of acute UGIB. Several randomized controlled trials are underway to determine whether TXA effectively reduces bleeding, rebleeding, or mortality in UGIB in all‐comers and patients with cirrhosis …”

Pharmacotherapeutic Management of Gastrointestinal Bleeding in Patients with Continuous‐Flow Left Ventricular Assist Devices

“…The authors analyzed seven double‐blind trials and did not find a significant difference between TXA and placebo on bleeding, surgery, or transfusion requirements. The Hemorrhage Alleviation with Tranexamic Acid – Intestinal System (HALT‐IT) study is an ongoing analysis evaluating whether early administration of TXA in patients with acute GIB lowers the risk of death . Although the study does not mention the inclusion of patients with CF‐LVADs, any potential benefits from the study could provide an alternative management strategy for management of acute GIB.…”