HALT-IT--tranexamic acid for the treatment of gastrointestinal bleeding: study
protocol for a randomised controlled trial.
Author(s): Roberts I, Coats T, Edwards P, Gilmore I, Jairath V, Ker K, Manno D(1), Shakur H,
Stanworth S, Veitch A.
Affiliation(s): Author information:
(1)Clinical Trials Unit, London School of Hygiene & Tropical Medicine, Keppel
Street, London WC1E 7HT, UK. Daniela.Manno@lshtm.ac.uk.
Publication date & source: 2014, Trials. , 15:450
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%.
TRIAL REGISTRATION: Current Controlled Trials ISRCTN11225767 (registration date:
3 July 2012); Clinicaltrials.gov NCT01658124 (registration date: 26 July 2012).
|