HEAT Helicobacter Eradication Aspirin Trial

This trial is based on evidence that peptic ulcer bleeding in aspirin users occurs predominantly in people infected with the ulcerogenic bacterium, Helicobacter pylori. The hypothesis is that low doses of aspirin do not cause ulcers in the way that high doses do. Instead we think that H. pylori causes the ulcer and aspirin, by thinning the blood, makes it bleed. If the bacterium is eradicated the patient will not get an ulcer and therefore there is no increased bleeding risk with aspirin.

Development of the trial protocol has been based on results of a preparatory MRC-funded 2525 patient pilot study which had a 47% patient response rate. This enabled the research team to design the currently proposed large simple outcomes study to investigate directly the hypothesis that a one week course of H. pylori eradication will halve the rate of hospitalisation due to ulcer bleeding over ~2.5 years in aspirin users.

A large number of patients (~120,000), using aspirin <326 mg daily will be invited to participate. Suitable respondents (~40,000) who are H. pylori positive (~10,000) will give consent (including access to HES and ONS mortality data) and be randomised to eradication treatment or placebo. There will be no follow-up trial visits for 90% of patients. Instead the MiQuest (Morbidity Information Query and Export Syntax) tool, developed to interrogate different GP electronic databases, will be used together with direct patient notification to identify all possible ulcer bleeding admissions. A random 10% sample will be identified in advance to report quality of life information and be breath tested at the end of the trial, to ensure that we are achieving similar eradication rates to those achieved in our pilot study (91%).

An expert panel will use validated methodology to adjudicate whether patients have suffered ulcer bleeding (primary endpoint). The trial will continue until 96 positively adjudicated events have occurred, to ensure it has the power to answer the question of whether H. pylori eradication reduces the risk of ulcer bleeding.