Helicobacter Eradication Aspirin Trial (HEAT)

• The rate of hospitalisation due to peptic ulcer bleeding in patients who enter the randomised study (only the first event per patient will be analysed), adjudicated by a blinded Committee as definite or probable. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  

• Other causes of gastrointestinal bleeding (adjudicated); these are predicted not to be affected by H. pylori eradication and will act as a specificity control. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  
• Cardiovascular outcomes (APTC (Anti Platelet Trialists Collaboration) endpoint, myocardial infarction and stroke, unadjudicated); these are predicted not to be affected. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  
• The incidence of detected uncomplicated ulcers. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  
• Ulcer site (Duodenal Ulcer vs. Gastric Ulcer). [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  
• GP-recorded and patient-reported dyspepsia. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  
• Need for proton pump inhibitor prescription or other antiulcer/dyspepsia medication. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  

BACKGROUND: Aspirin use is widespread and increasing in elderly patients. The main hazard is gastrointestinal bleeding, the incidence of which is rising, probably because of increased aspirin use. The proposed trial is based on evidence that peptic ulcer bleeding in aspirin users occurs predominantly in people infected with the ulcerogenic bacterium, Helicobacter pylori. Our 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 Medical Research Council-funded 2525 patient pilot study which had a 47% patient response rate. This enabled us 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.

TRIAL CONDUCT: 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 Hospital Episode Statistics and Office of National Statistics 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 tool, developed to interrogate different GP electronic databases, will be used together with direct patient notification to identify all possible ulcer bleeding admissions. 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.