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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 : November 30, 2017
Sponsor:
Collaborators:
Nottingham University Hospitals NHS Trust
University of Southampton
University of Durham
University of Birmingham
University of Oxford
Queen's University, Belfast
Information provided by (Responsible Party):
University of Nottingham

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.


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

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 30024 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Helicobacter Eradication to Prevent Ulcer Bleeding in Aspirin Users: a Large Simple Randomised Controlled Trial
Study Start Date : March 2012
Actual Primary Completion Date : October 31, 2017
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding
U.S. FDA Resources

Arm Intervention/treatment
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
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.



Primary Outcome Measures :
  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. [ Time Frame: 4 years ]

Secondary Outcome Measures :
  1. 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 ]
  2. Cardiovascular outcomes (APTC (Anti Platelet Trialists Collaboration) endpoint, myocardial infarction and stroke, unadjudicated); these are predicted not to be affected. [ Time Frame: 4 years ]
  3. The incidence of detected uncomplicated ulcers. [ Time Frame: 4 years ]
  4. Ulcer site (Duodenal Ulcer vs. Gastric Ulcer). [ Time Frame: 4 years ]
  5. GP-recorded and patient-reported dyspepsia. [ Time Frame: 4 years ]
  6. Need for proton pump inhibitor prescription or other antiulcer/dyspepsia medication. [ Time Frame: 4 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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 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.

Information from the National Library of Medicine

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


Locations
United Kingdom
Queen's University
Belfast, United Kingdom, BT9 7HR
University of Birmingham
Birmingham, United Kingdom, B15 2TT
Durham University
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
Sponsors and Collaborators
University of Nottingham
Nottingham University Hospitals NHS Trust
University of Southampton
University of Durham
University of Birmingham
University of Oxford
Queen's University, Belfast
Investigators
Principal Investigator: Chris J Hawkey University of Nottingham

Additional Information:
Publications:
Responsible Party: University of Nottingham
ClinicalTrials.gov Identifier: NCT01506986     History of Changes
Other Study ID Numbers: 11091
09/55/52 ( Other Grant/Funding Number: NIHR HTA )
2011-003425-96 ( EudraCT Number )
ISRCTN10134725 ( Registry Identifier: ISRCTN )
First Posted: January 10, 2012    Key Record Dates
Last Update Posted: November 30, 2017
Last Verified: November 2017

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

Additional relevant MeSH terms:
Ulcer
Hemorrhage
Bacterial Infections
Pathologic Processes
Aspirin
Clarithromycin
Lansoprazole
Dexlansoprazole
Metronidazole
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Anti-Infective Agents
Antiprotozoal Agents
Antiparasitic Agents
Anti-Bacterial Agents
Protein Synthesis Inhibitors
Cytochrome P-450 CYP3A Inhibitors