Helicobacter Eradication Aspirin Trial

NCT01506986 | Completed Phase 4 DMC

• 4 other identifiers: 1109109/55/522011-003425-96ISRCTN10134725
• Study Type: interventional
• Target: 30,024
• Locations: 1 country
• Sites: 6

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.

Conditions

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

Keywords

Ulcer bleeding; Aspirin; Helicobacter pylori; H. pylori; Hospitalisation for ulcer bleeding

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  4 years

• Cardiovascular outcomes (APTC (Anti Platelet Trialists Collaboration) endpoint, myocardial infarction and stroke, unadjudicated); these are predicted not to be affected.

  4 years

• The incidence of detected uncomplicated ulcers.

  4 years

• Ulcer site (Duodenal Ulcer vs. Gastric Ulcer).

  4 years

• GP-recorded and patient-reported dyspepsia.

  4 years

Study Arms (2)

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.

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.

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

Interventions

Lansoprazole 30mg, Clarithromycin 500mg, Metronidazole 400mg DRUG

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

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

H. pylori eradication treatment

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

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

Placebo H. pylori eradication treatment

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Nottingham: lead
• Nottingham University Hospitals NHS Trust: collaborator
• University of Southampton: collaborator
• University of Durham: collaborator
• University of Birmingham: collaborator
• University of Oxford: collaborator
• Queen's University, Belfast: collaborator

Study Sites (6)

Queen's University

Belfast, BT9 7HR, United Kingdom

Location

University of Birmingham

Birmingham, B15 2TT, United Kingdom

Location

Durham University

Durham, TS17 6BH, United Kingdom

Location

University of Nottingham

Nottingham, NG7 2UH, United Kingdom

Location

University of Oxford

Oxford, OX1 2ET, United Kingdom

Location

University of Southampton

Southampton, SO16 5ST, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 26501118 BACKGROUND

• 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.

  PMID: 40844182 DERIVED

• 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.

  PMID: 35164864 DERIVED

MeSH Terms

Interventions

Lansoprazole; Clarithromycin; Metronidazole

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Erythromycin; Macrolides; Polyketides; Lactones; Nitroimidazoles; Nitro Compounds; Imidazoles; Azoles

Study Officials

• Chris J Hawkey

  University of Nottingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2012
• First Posted: January 10, 2012
• Study Start: March 1, 2012
• Primary Completion: October 31, 2017
• Study Completion: March 16, 2022
• Last Updated: May 17, 2022

Record last verified: 2022-05

Locations

GB (6)