Tranexamic acid for acute gastrointestinal bleeding (the HALT-IT trial): statistical analysis plan for an international, randomised, double-blind, placebo-controlled trial.pdf (864.94 kB)
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Tranexamic acid for acute gastrointestinal bleeding (the HALT-IT trial): statistical analysis plan for an international, randomised, double-blind, placebo-controlled trial.

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posted on 07.10.2019, 08:15 by A Brenner, A Afolabi, SM Ahmad, M Arribas, R Chaudhri, T Coats, J Cuzick, I Gilmore, C Hawkey, V Jairath, K Javaid, A Kayani, M Mutti, MA Nadeem, H Shakur-Still, S Stanworth, A Veitch, I Roberts, HALT-IT Trial Collaborators
BACKGROUND: Acute gastrointestinal (GI) bleeding is an important cause of mortality worldwide. Bleeding can occur from the upper or lower GI tract, with upper GI bleeding accounting for most cases. The main causes include peptic ulcer/erosive mucosal disease, oesophageal varices and malignancy. The case fatality rate is around 10% for upper GI bleeding and 3% for lower GI bleeding. Rebleeding affects 5-40% of patients and is associated with a four-fold increased risk of death. Tranexamic acid (TXA) decreases bleeding and the need for blood transfusion in surgery and reduces death due to bleeding in patients with trauma and postpartum haemorrhage. It reduces bleeding by inhibiting the breakdown of fibrin clots by plasmin. Due to the methodological weaknesses and small size of the existing trials, the effectiveness and safety of TXA in GI bleeding is uncertain. The Haemorrhage ALleviation with Tranexamic acid - Intestinal system (HALT-IT) trial aims to provide reliable evidence about the effects of TXA in acute upper and lower GI bleeding. METHODS: The HALT-IT trial is an international, randomised, double-blind, placebo-controlled trial of tranexamic acid in 12,000 adults (increased from 8000) with acute upper or lower GI bleeding. Eligible patients are randomly allocated to receive TXA (1-g loading dose followed by 3-g maintenance dose over 24 h) or matching placebo. The main analysis will compare those randomised to TXA with those randomised to placebo on an intention-to-treat basis, presenting the results as effect estimates (relative risks) and confidence intervals. The primary outcome is death due to bleeding within 5 days of randomisation and secondary outcomes are: rebleeding; all-cause and cause-specific mortality; thromboembolic events; complications; endoscopic, radiological and surgical interventions; blood transfusion requirements; disability (defined by a measure of patient's self-care capacity); and number of days spent in intensive care or high-dependency units. Subgroup analyses for the primary outcome will consider time to treatment, location of bleeding, cause of bleed and clinical Rockall score. DISCUSSION: We present the statistical analysis of the HALT-IT trial. This plan was published before the treatment allocation was unblinded. TRIAL REGISTRATION: Current Controlled Trials, ID: ISRCTN11225767. Registered on 3 July 2012;, ID: NCT01658124. Registered on 26 July 2012.


Funding for the HALT-IT trial is provided by the UK National Institute for Health Research Health Technology Assessment Programme. Funding covers trial materials, meetings and central organisational costs. The funders for the trials had no role in study design, data collection, analysis or interpretation or the writing of this manuscript.



Trials, 2019, volume 20, Article number: 467

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/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Cardiovascular Sciences


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The datasets generated and/or analysed during the current study are not yet publicly available because the trial is ongoing. Once recruitment has stopped and after publication of the planned primary and secondary analyses, the trial data will be made available via our data-sharing portal, The Free Bank of Injury and Emergency Research Data (freeBIRD) website at Additional file 1 Figure S1 Trial profile. Figure S2 Cumulative percentage of death due to bleeding in the tranexamic acid and placebo groups. Figure S3 Distribution of cause of death by days since randomisation. Table S1 Baseline characteristics of participants prior to randomisation. Table S2 Death due to bleeding and rebleeding. Table S3 Other causes of death and all-cause mortality. Table S4 Death due to bleeding by subgroups. Table S5 Need for surgical, endoscopic and radiological interventions and blood transfusion. Table S6 Thromboembolic events, complications and self-care capacity. Table S7 Adverse events. (DOC 355 kb)