Helicobacter Eradication Aspirin Trial

NCT ID: NCT01506986

Last Updated: 2022-05-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 30024 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-31
• Study Completion Date: 2022-03-16

Brief Summary

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.

Detailed Description

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.

Conditions

Gastrointestinal Ulcer Haemorrhage; Bacterial Infection Due to Helicobacter Pylori (H. Pylori)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Lansoprazole 30mg, Clarithromycin 500mg, Metronidazole 400mg

Intervention Type: DRUG

All three medications will be taken orally, twice daily, for seven days.

Placebo H. pylori eradication treatment

Placebos to seven days of lansoprazole 30mg twice daily, clarithromycin 500mg twice daily and metronidazole 400mg twice daily.

Group Type: PLACEBO_COMPARATOR

Placebo lansoprazole 30mg, clarithromycin 500mg, metronidazole 400mg

Intervention Type: DRUG

Medication to be taken orally, twice a day, for seven days.

Interventions

Lansoprazole 30mg, Clarithromycin 500mg, Metronidazole 400mg

All three medications will be taken orally, twice daily, for seven days.

Intervention Type: DRUG

Placebo lansoprazole 30mg, clarithromycin 500mg, metronidazole 400mg

Medication to be taken orally, twice a day, for seven days.

Intervention Type: DRUG

Other Intervention Names

Lansoprazole (CAS: 103577-45-3); 30mg capsules.; Clarithromycin (CAS: 81103-11-9); 500mg tablets.; Metronidazole (CAS: 99616-64-5) 400mg tablets.

Eligibility Criteria

Inclusion Criteria

• Males and females ≥ 60 years of age at the date of screening.
• Subjects who are taking aspirin ≤325mg daily and who have had 4 or more 28-day prescriptions in the last year.
• Subjects who are concurrently using other anti-platelet agents are allowed to enter the study.
• Subjects who are willing and able to undergo a breath test for H. pylori, including fasting for 6 hours, and whose result is unequivocally positive (results of breath test will be determined post-screening).
• Subjects who are willing to give permission for their paper and electronic medical records to be accessed and abstracted by trial investigators.
• Subjects who are willing to be contacted and interviewed by trial investigators, should the need arise for adverse event assessment, etc.
• Subjects must be able to communicate well with the investigator or designee, to understand and comply with the requirements of the study and to understand and sign the written informed consent.

Exclusion Criteria

• Subjects who are currently prescribed anti-ulcer therapy such as H2-receptor antagonists and proton-pump inhibitors.
• Subjects who are currently prescribed oral non-steroidal anti-inflammatory drugs (NSAIDs).
• Subjects who have a known intolerance or allergy to H. pylori eradication treatment.
• Subjects who are taking drugs with a clinically significant interaction with H. pylori eradication treatment.
• Subjects who are terminally ill or suffer from a life-threatening co-morbidity.
• Subjects whose behaviour or lifestyle would render them less likely to comply with study medication (eg. alcoholism, substance abuse, debilitating psychiatric conditions or inability to provide informed consent).
• Subjects currently participating in another interventional clinical trial or who have taken part in a trial in the previous three months.

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nottingham University Hospitals NHS Trust

OTHER

Sponsor Role: collaborator

University of Southampton

OTHER

Sponsor Role: collaborator

University of Durham

OTHER

Sponsor Role: collaborator

University of Birmingham

OTHER

Sponsor Role: collaborator

University of Oxford

OTHER

Sponsor Role: collaborator

Queen's University, Belfast

OTHER

Sponsor Role: collaborator

University of Nottingham

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chris J Hawkey

Role: PRINCIPAL_INVESTIGATOR

University of Nottingham

Locations

Queen's University

Belfast, , United Kingdom

University of Birmingham

Birmingham, , United Kingdom

Durham University

Durham, , United Kingdom

University of Nottingham

Nottingham, , United Kingdom

University of Oxford

Oxford, , United Kingdom

University of Southampton

Southampton, , United Kingdom

Countries

United Kingdom

References

Dumbleton JS, Avery AJ, Coupland C, Hobbs FD, Kendrick D, Moore MV, Morris C, Rubin GP, Smith MD, Stevenson DJ, Hawkey CJ. The Helicobacter Eradication Aspirin Trial (HEAT): A Large Simple Randomised Controlled Trial Using Novel Methodology in Primary Care. EBioMedicine. 2015 Jul 10;2(9):1200-4. doi: 10.1016/j.ebiom.2015.07.012. eCollection 2015 Sep.

Reference Type: BACKGROUND

PMID: 26501118 (View on PubMed)

Hawkey CJ, Avery AJ, Coupland CA, Crooks CJ, Dumbleton JS, Hobbs FR, Kendrick D, Moore M, Morris C, Rubin G, Smith M, Stevenson D; HEAT trialists. Eradication of Helicobacter pylori for prevention of aspirin-associated peptic ulcer bleeding in adults over 65 years: the HEAT RCT. Health Technol Assess. 2025 Aug;29(42):1-62. doi: 10.3310/LLKF7871.

Reference Type: DERIVED

PMID: 40844182 (View on PubMed)

Stevenson DJ, Avery AJ, Coupland C, Hobbs FDR, Kendrick D, Moore MV, Morris C, Rubin GP, Smith MD, Hawkey CJ, Dumbleton JS. Recruitment to a large scale randomised controlled clinical trial in primary care: the Helicobacter Eradication Aspirin Trial (HEAT). Trials. 2022 Feb 14;23(1):140. doi: 10.1186/s13063-022-06054-w.

Reference Type: DERIVED

PMID: 35164864 (View on PubMed)

Other Identifiers

09/55/52

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2011-003425-96

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ISRCTN10134725

Identifier Type: REGISTRY

Identifier Source: secondary_id

11091

Identifier Type: -

Identifier Source: org_study_id