Gastrointestinal Ulcer HaemorrhagePhase 4HEATNCT01506986
Helicobacter Eradication Aspirin Trial
A Phase 4 study testing Lansoprazole 30mg, Clarithromycin 500mg, Metronidazole 400mg in people with Gastrointestinal Ulcer Haemorrhage and Bacterial Infection Due to Helicobacter Pylori (H. Pylori), run by University of Nottingham at 6 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Gastrointestinal Ulcer Haemorrhage, Bacterial Infection Due to Helicobacter Pylori (H. Pylori)
- What is being tested?
- Lansoprazole 30mg, Clarithromycin 500mg, Metronidazole 400mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30,024 participants
- Where
- 6 sitesUnited Kingdom
- Study dates
- Mar 2012to 16 Mar 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United Kingdom6 sites
Queen's University
Belfast, BT9 7HR
University of Birmingham
Birmingham, B15 2TT
Durham University
Durham, TS17 6BH
University of Nottingham
Nottingham, NG7 2UH
University of Oxford
Oxford, OX1 2ET
University of Southampton
Southampton, SO16 5ST
About this study
Official title: Helicobacter Eradication to Prevent Ulcer Bleeding in Aspirin Users: a Large Simple Randomised Controlled Trial
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.
Read more
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.
Read the 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)
- Being tested
- Lansoprazole 30mg, Clarithromycin 500mg, Metronidazole 400mg, Placebo lansoprazole 30mg, clarithromycin 500mg, metronidazole 400mg
- Keywords
- Ulcer bleeding, Aspirin, Helicobacter pylori, H. pylori, Hospitalisation for ulcer bleeding
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lansoprazole 30mg, Clarithromycin 500mg, Metronidazole 400mgDrug
Also called Lansoprazole (CAS: 103577-45-3); 30mg capsules., Clarithromycin (CAS: 81103-11-9); 500mg tablets., Metronidazole (CAS: 99616-64-5) 400mg tablets.
All three medications will be taken orally, twice daily, for seven days.
Placebo lansoprazole 30mg, clarithromycin 500mg, metronidazole 400mgDrug
Medication to be taken orally, twice a day, for seven days.
| Study group | Role | What they receive |
|---|---|---|
| H. pylori eradication treatment | Active comparator | Active treatment will consist of seven days of lansoprazole 30mg twice daily, clarithromycin 500mg twice daily and metronidazole 400mg twice daily. Receives: Drug: Lansoprazole 30mg, Clarithromycin 500mg, Metronidazole 400mg |
| Placebo H. pylori eradication treatment | Placebo comparator | Placebos to seven days of lansoprazole 30mg twice daily, clarithromycin 500mg twice daily and metronidazole 400mg twice daily. Receives: Drug: Placebo lansoprazole 30mg, clarithromycin 500mg, metronidazole 400mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 years
Secondary outcomes (6)
Other causes of gastrointestinal bleeding (adjudicated); these are predicted not to be affected by H. pylori eradication and will act as a specificity control.
Measured: 4 years
Cardiovascular outcomes (APTC (Anti Platelet Trialists Collaboration) endpoint, myocardial infarction and stroke, unadjudicated); these are predicted not to be affected.
Measured: 4 years
The incidence of detected uncomplicated ulcers.
Measured: 4 years
Ulcer site (Duodenal Ulcer vs. Gastric Ulcer).
Measured: 4 years
GP-recorded and patient-reported dyspepsia.
Measured: 4 years
Need for proton pump inhibitor prescription or other antiulcer/dyspepsia medication.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2012 (estimated)
- Study startMar 2012
- Primary completion31 Oct 2017
- Study completion16 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Gastrointestinal Ulcer HaemorrhageStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30,024 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Collaborators
- Nottingham University Hospitals NHS Trust, University of Southampton, University of Durham, University of Birmingham, University of Oxford, Queen's University, Belfast
- Responsible party
- Sponsor
- Investigators
- Chris J Hawkey, Principal investigator, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01506986
- Sponsor's protocol ID
- 11091
- Other IDs
- 09/55/52, 2011-003425-96, ISRCTN10134725
- Acronym
- HEAT
- Status last verified
- May 2022
- First submitted
- 5 Jan 2012
- Last updated
- 17 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 26501118Hawkey 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.
PubMed 40844182Stevenson 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.
PubMed 35164864
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Helicobacter Eradication to Prevent Ulcer Bleeding in Aspirin Users: a Large Simple Randomised Controlled Trial
- ClinicalTrials.gov ID
- NCT01506986
- Acronym / sponsor ID
- HEAT / 11091
- Conditions
- Gastrointestinal Ulcer Haemorrhage, Bacterial Infection Due to Helicobacter Pylori (H. Pylori)
- Keywords
- Ulcer bleeding, Aspirin, Helicobacter pylori, H. pylori, Hospitalisation for ulcer bleeding
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30,024 participants (actual)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Collaborators
- Nottingham University Hospitals NHS Trust, University of Southampton, University of Durham, University of Birmingham, University of Oxford, Queen's University, Belfast
- Study start
- Mar 2012 (actual)
- Primary completion
- 31 Oct 2017 (actual)
- Study completion
- 16 Mar 2022 (actual)
- First posted
- 10 Jan 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| H. pylori eradication treatment | Active comparator | Drug: Lansoprazole 30mg, Clarithromycin 500mg, Metronidazole 400mgActive treatment will consist of seven days of lansoprazole 30mg twice daily, clarithromycin 500mg twice daily and metronidazole 400mg twice daily. |
| Placebo H. pylori eradication treatment | Placebo comparator | Drug: Placebo lansoprazole 30mg, clarithromycin 500mg, metronidazole 400mgPlacebos to seven days of lansoprazole 30mg twice daily, clarithromycin 500mg twice daily and metronidazole 400mg twice daily. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lansoprazole 30mg, Clarithromycin 500mg, Metronidazole 400mgAlso: Lansoprazole (CAS: 103577-45-3); 30mg capsules., Clarithromycin (CAS: 81103-11-9); 500mg tablets., Metronidazole (CAS: 99616-64-5) 400mg tablets.All three medications will be taken orally, twice daily, for seven days. | Drug | H. pylori eradication treatment |
| Placebo lansoprazole 30mg, clarithromycin 500mg, metronidazole 400mgMedication to be taken orally, twice a day, for seven days. | Drug | Placebo H. pylori eradication treatment |
Primary outcome
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
6 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2022.
- Background: PubMed 26501118Dumbleton 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.
- Derived from this study: PubMed 40844182Hawkey 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.
- Derived from this study: PubMed 35164864Stevenson 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chris J Hawkey principal investigator
University of Nottingham
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Lansoprazole 30mg, Clarithromycin 500mg, Metronidazole 400mg in people with Gastrointestinal Ulcer Haemorrhage and Bacterial Infection Due to Helicobacter Pylori (H. Pylori), run by University of Nottingham at 6 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01506986, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2022; AzTrials last refreshed its copy on 30 Oct 2026.