title: HALT-IT--tranexamic acid for the treatment of gastrointestinal bleeding: study protocol for a randomised controlled trial.
abstract: BACKGROUND
  Gastrointestinal 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.
  
  
  METHODS
  HALT-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%.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN11225767 (registration date: 3 July 2012); Clinicaltrials.gov NCT01658124 (registration date: 26 July 2012).
authors.forename: Ian
authors.initials: I
authors.lastname: Roberts
authors.forename: Timothy
authors.initials: T
authors.lastname: Coats
authors.forename: Phil
authors.initials: P
authors.lastname: Edwards
authors.forename: Ian
authors.initials: I
authors.lastname: Gilmore
authors.forename: Vipul
authors.initials: V
authors.lastname: Jairath
authors.forename: Katharine
authors.initials: K
authors.lastname: Ker
authors.affiliation: Clinical Trials Unit, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK. Daniela.Manno@lshtm.ac.uk.
authors.forename: Daniela
authors.initials: D
authors.lastname: Manno
authors.forename: Haleema
authors.initials: H
authors.lastname: Shakur
authors.forename: Simon
authors.initials: S
authors.lastname: Stanworth
authors.forename: Andrew
authors.initials: A
authors.lastname: Veitch
mesh_terms: D000933:Antifibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001803:Blood Transfusion; D002985:Clinical Protocols; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006471:Gastrointestinal Hemorrhage / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007262:Infusions, Intravenous; D057194:Intention to Treat Analysis; D012008:Recurrence; D012107:Research Design; D013997:Time Factors; D014148:Tranexamic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid