Helicobacter Eradication Aspirin Trial (HEAT)
HEAT (Helicobacter Eradication Aspirin Trial) is a large simple double-blind placebo controlled outcomes study of Helicobacter pylori (H. pylori) eradication to prevent ulcer bleeding in aspirin users. It will be run by the University of Nottingham, with recruiting centres across the UK. This trial is funded by the National Institute of Health Research Health Technology Assessment (NIHR HTA) Programme.
Aspirin use is widespread and increasing in elderly patients. The main hazard is gastrointestinal bleeding, which may be increasing because of increasing aspirin use. This trial is based on evidence that peptic ulcer bleeding in aspirin users occurs predominantly in H. pylori positive people.
Patients will be identified by their GPs, then asked to attend an appointment with a Research Nurse to consent to the trial and take a H. pylori breath test. Those with a positive result will be randomised to receive a one week course of either eradication treatment or placebo. No follow-up visits are required, but instead information will be extracted from the patients' electronic medical record using the MiQuest search tool.
The trial will continue until 87 adjudicated events (hospitalisation because of definite or probable peptic ulcer bleeding) have occurred, which would occur after a mean 2.5 patient years of follow-up, if trial assumptions are correct.
|Gastrointestinal Ulcer Haemorrhage Bacterial Infection Due to Helicobacter Pylori (H. Pylori)||Drug: Lansoprazole 30mg, Clarithromycin 500mg, Metronidazole 400mg Drug: Placebo lansoprazole 30mg, clarithromycin 500mg, metronidazole 400mg||Phase 4|
|Study Design:||Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Helicobacter Eradication to Prevent Ulcer Bleeding in Aspirin Users: a Large Simple Randomised Controlled Trial|
- 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 ]
- 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 ]
- Cardiovascular outcomes (APTC (Anti Platelet Trialists Collaboration) endpoint, myocardial infarction and stroke, unadjudicated); these are predicted not to be affected. [ Time Frame: 4 years ]
- The incidence of detected uncomplicated ulcers. [ Time Frame: 4 years ]
- Ulcer site (Duodenal Ulcer vs. Gastric Ulcer). [ Time Frame: 4 years ]
- GP-recorded and patient-reported dyspepsia. [ Time Frame: 4 years ]
- Need for proton pump inhibitor prescription or other antiulcer/dyspepsia medication. [ Time Frame: 4 years ]
|Study Start Date:||March 2012|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||April 2017 (Final data collection date for primary outcome measure)|
Active Comparator: H. pylori eradication treatment
Active treatment will consist of seven days of lansoprazole 30mg twice daily, clarithromycin 500mg twice daily and metronidazole 400mg twice daily.
Drug: Lansoprazole 30mg, Clarithromycin 500mg, Metronidazole 400mg
All three medications will be taken orally, twice daily, for seven days.
Placebo Comparator: Placebo H. pylori eradication treatment
Placebos to seven days of lansoprazole 30mg twice daily, clarithromycin 500mg twice daily and metronidazole 400mg twice daily.
Drug: Placebo lansoprazole 30mg, clarithromycin 500mg, metronidazole 400mg
Medication to be taken orally, twice a day, for seven days.
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 (~170,000), using aspirin <326 mg daily will be invited to participate. Suitable respondents (~33,000) who are H. pylori positive (~6,600) 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 87 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01506986
|Contact: Chris J Hawkey||+44(0)firstname.lastname@example.org|
|Contact: Jennifer S Dumbleton||+44(0)email@example.com|
|Belfast, United Kingdom, BT9 7HR|
|Contact: Margaret Cupples 02890 204252 firstname.lastname@example.org|
|Contact: Claire Leathem 02890 204316 email@example.com|
|Principal Investigator: Margaret Cupples|
|University of Birmingham||Recruiting|
|Birmingham, United Kingdom, B15 2TT|
|Contact: Richard Hobbs +44(0)1865289288 firstname.lastname@example.org|
|Contact: Rachel Iles email@example.com|
|Durham, United Kingdom, TS17 6BH|
|Contact: Greg Rubin +44(0)1913340031 firstname.lastname@example.org|
|Contact: Andrew Moreton 0191 3340343 email@example.com|
|Principal Investigator: Greg Rubin|
|University of Nottingham||Recruiting|
|Nottingham, United Kingdom, NG7 2UH|
|Contact: Chris J Hawkey +44(0)1158231031 firstname.lastname@example.org|
|Contact: Jennifer S Dumbleton +44(0)1158231053 email@example.com|
|Principal Investigator: Chris J Hawkey|
|University of Oxford||Recruiting|
|Oxford, United Kingdom, OX1 2ET|
|Contact: Richard Hobbs +44(0)1865289288 firstname.lastname@example.org|
|Contact: Mina Davoudianfar 01865 289336 email@example.com|
|Principal Investigator: Richard Hobbs|
|University of Southampton||Recruiting|
|Southampton, United Kingdom, SO16 5ST|
|Contact: Michael Moore +44(0)2380241055 firstname.lastname@example.org|
|Contact: Wendy O'Brien 02380 241054 email@example.com|
|Principal Investigator: Michael Moore|
|Principal Investigator:||Chris J Hawkey||University of Nottingham|