Helicobacter Eradication Aspirin Trial (HEAT)
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|ClinicalTrials.gov Identifier: NCT01506986|
Recruitment Status : Active, not recruiting
First Posted : January 10, 2012
Last Update Posted : March 24, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|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|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||30024 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Helicobacter Eradication to Prevent Ulcer Bleeding in Aspirin Users: a Large Simple Randomised Controlled Trial|
|Actual Study Start Date :||March 2012|
|Actual Primary Completion Date :||October 31, 2017|
|Estimated Study Completion Date :||April 2021|
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.
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01506986
|Belfast, United Kingdom, BT9 7HR|
|University of Birmingham|
|Birmingham, United Kingdom, B15 2TT|
|Durham, United Kingdom, TS17 6BH|
|University of Nottingham|
|Nottingham, United Kingdom, NG7 2UH|
|University of Oxford|
|Oxford, United Kingdom, OX1 2ET|
|University of Southampton|
|Southampton, United Kingdom, SO16 5ST|
|Principal Investigator:||Chris J Hawkey||University of Nottingham|