Helicobacter Eradication Aspirin Trial (HEAT)

This study is currently recruiting participants.
Verified January 2014 by University of Nottingham
Sponsor:
Collaborators:
Nottingham University Hospitals NHS Trust
University of Southampton
University of Durham
University of Birmingham
University of Oxford
Information provided by (Responsible Party):
University of Nottingham
ClinicalTrials.gov Identifier:
NCT01506986
First received: January 5, 2012
Last updated: January 16, 2014
Last verified: January 2014
  Purpose

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 will take place in approximately 57 Primary Care Trusts (PCTs) and 12 Comprehensive Local Research Networks (CLRNs), and 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 96 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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Helicobacter Eradication to Prevent Ulcer Bleeding in Aspirin Users: a Large Simple Randomised Controlled Trial

Resource links provided by NLM:


Further study details as provided by University of Nottingham:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • Cardiovascular outcomes (APTC (Anti Platelet Trialists Collaboration) endpoint, myocardial infarction and stroke, unadjudicated); these are predicted not to be affected. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  • The incidence of detected uncomplicated ulcers. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  • Ulcer site (Duodenal Ulcer vs. Gastric Ulcer). [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  • GP-recorded and patient-reported dyspepsia. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  • Need for proton pump inhibitor prescription or other antiulcer/dyspepsia medication. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40000
Study Start Date: March 2012
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Other Names:
  • Lansoprazole (CAS: 103577-45-3); 30mg capsules.
  • Clarithromycin (CAS: 81103-11-9); 500mg tablets.
  • Metronidazole (CAS: 99616-64-5) 400mg tablets.
Placebo Comparator: Placebo H. pylori eradication treatment
Exact matching 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.

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 (~120,000), using aspirin <326 mg daily will be invited to participate. Suitable respondents (~40,000) who are H. pylori positive (~10,000) 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 96 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.

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 taking anti-ulcer therapy such as H2-receptor antagonists and proton-pump inhibitors.
  • Subjects who are currently taking 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01506986

Contacts
Contact: Chris J Hawkey +44(0)1158231031 cj.hawkey@nottingham.ac.uk
Contact: Jennifer S Dumbleton +44(0)1158231053 jennifer.dumbleton@nottingham.ac.uk

Locations
United Kingdom
University of Birmingham Recruiting
Birmingham, United Kingdom, B15 2TT
Contact: Richard Hobbs    +44(0)1865289288    richard.hobbs@phc.ox.ac.uk   
Contact: Rachel Iles       r.iles@bham.ac.uk   
Durham University Recruiting
Durham, United Kingdom, TS17 6BH
Contact: Greg Rubin    +44(0)1913340031    g.p.rubin@durham.ac.uk   
Principal Investigator: Greg Rubin         
University of Nottingham Recruiting
Nottingham, United Kingdom, NG7 2UH
Contact: Chris J Hawkey    +44(0)1158231031    cj.hawkey@nottingham.ac.uk   
Contact: Jennifer S Dumbleton    +44(0)1158231053    jennifer.dumbleton@nottingham.ac.uk   
Principal Investigator: Chris J Hawkey         
University of Oxford Recruiting
Oxford, United Kingdom, OX1 2ET
Contact: Richard Hobbs    +44(0)1865289288    richard.hobbs@phc.ox.ac.uk   
Contact: Maria Breen       maria.breen@phc.ox.ac.uk   
Principal Investigator: Richard Hobbs         
University of Southampton Recruiting
Southampton, United Kingdom, SO16 5ST
Contact: Mike Moore    +44(0)2380241055    mvm198@soton.ac.uk   
Principal Investigator: Mike Moore         
Sponsors and Collaborators
University of Nottingham
Nottingham University Hospitals NHS Trust
University of Southampton
University of Durham
University of Birmingham
University of Oxford
Investigators
Principal Investigator: Chris J Hawkey University of Nottingham
  More Information

Additional Information:
No publications provided

Responsible Party: University of Nottingham
ClinicalTrials.gov Identifier: NCT01506986     History of Changes
Other Study ID Numbers: 11091, 09/55/52, 2011-003425-96, ISRCTN10134725
Study First Received: January 5, 2012
Last Updated: January 16, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Institute for Health Research
United Kingdom: Research Ethics Committee

Keywords provided by University of Nottingham:
Ulcer bleeding
Aspirin
Helicobacter pylori
H. pylori
Hospitalisation for ulcer bleeding

Additional relevant MeSH terms:
Bacterial Infections
Hemorrhage
Ulcer
Pathologic Processes
Aspirin
Lansoprazole
Clarithromycin
Metronidazole
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Central Nervous System Agents
Radiation-Sensitizing Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on April 15, 2014