Condition category
Digestive System
Date applied
19/12/2011
Date assigned
28/12/2011
Last edited
01/09/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Aspirin is a medicine that reduces the risk of clots forming in your blood. Aspirin use is widespread and increasing in elderly patients. The main side effect is gastrointestinal (digestive tract) bleeding, the incidence of which is rising, probably because of increased aspirin use. We think that the bacterium Helicobacter pylori causes stomach ulcers and aspirin, by thinning the blood, makes the ulcers bleed. If the bacterium is eradicated the patient will not get an ulcer and therefore there is no increased bleeding risk with aspirin. The aim of this study is to find out whether a one-week course of H. pylori eradication will reduce the rate of hospitalisation due to ulcer bleeding.

Who can participate?
Patients over 60 using aspirin daily who are infected with H. pylori.

What does the study involve?
Participants are randomly allocated to either treatment to eradicate H. pylori or placebo (dummy tablets). There will be no follow-up visits for 90% of patients. Instead we will use GP electronic databases to identify hospital admissions for ulcer bleeding. A random sample of participants will be breath tested at the end of the study to ensure that we are achieving similar H. pylori eradication rates to those achieved in our previous study.

What are the possible benefits and risks of participating?
A positive result would increase patient safety, reduce hospitalisations for gastrointestinal bleeding, reduce premature death, decrease medical costs and expand the number of patients for whom aspirin is beneficial.

Where is the study run from?
Nottingham Digestive Diseases Centre (UK)

When is the study starting and how long is it expected to run for?
March 2012 to April 2017

Who is funding the study?
NIHR Health Technology Assessment Programme - HTA (UK)

Who is the main contact?
Jennifer Dumbleton
jennifer.dumbleton@nottingham.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Prof Chris Hawkey

ORCID ID

Contact details

Nottingham Digestive Diseases Centre
University Hospital
Nottingham
NG7 2UH
United Kingdom

Type

Scientific

Additional contact

Ms Jennifer Dumbleton

ORCID ID

http://orcid.org/0000-0001-9099-5555

Contact details

Nottingham Digestive Diseases Centre
University Hospital
Nottingham
NG7 2UH
United Kingdom

Additional identifiers

EudraCT number

2011-003425-96

ClinicalTrials.gov number

NCT01506986

Protocol/serial number

11091

Study information

Scientific title

Helicobacter eradication to prevent ulcer bleeding in aspirin users: a large simple randomised controlled trial

Acronym

HEAT

Study hypothesis

Current hypothesis as of 25/05/2016:
A one week course of Helicobacter pylori (H. pylori) eradication in patients using aspirin (less than 325mg) daily will reduce the incidence of subsequent adjudicated peptic ulcer bleeding which results in hospitalisation.

Previous hypothesis:
A one week course of Helicobacter pylori (H. pylori) eradication in patients using aspirin (325mg) daily will reduce the incidence of subsequent adjudicated peptic ulcer bleeding which results in hospitalisation.

More details can be found at: http://www.nets.nihr.ac.uk/projects/hta/095552
Protocol can be found at: http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0006/54555/PRO-09-55-52.pdf

Ethics approval

East Midlands Research Ethics Committee, 08/12/2011, ref: 11/EM/0434

Study design

Double-blind placebo-controlled randomised multi-centre study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

GP practices

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Patients using aspirin less than 325mg daily

Intervention

Active treatment will consist of seven days of lansoprazole 30mg, clarithromycin 500mg and metronidazole 400mg all given twice daily. This is one of the authorised recommended regimens for H. pylori eradication in adults. The control group will receive placebos to the same regimen:

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

Current interventions as of 25/05/2016:
The trial will continue until 87 adjudicated events have occurred, which would occur after a mean 2.5 patient years of follow-up, if trial assumptions are correct.

Previous interventions:
The trial will continue until 96 adjudicated events have occurred, which would occur after a mean 2.5 patient years of follow-up, if trial assumptions are correct.

Intervention type

Drug

Phase

Not Applicable

Drug names

Clarithromycin, lansoprazole, metronidazole

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. The committee will use definitions validated in the TARGET study.

Secondary outcome measures

1. Other causes of GI bleeding (adjudicated); these are predicted not to be affected by H. pylori eradication and will act as a specificity control
2. Cardiovascular outcomes (APTC endpoint, MI and stroke, unadjudicated); these are predicted not to be affected
3. The incidence of detected uncomplicated ulcers
4. Ulcer site (Duodenal Ulcer vs. Gastric Ulcer)
5. GP-recorded and patient-reported dyspepsia
6. Need for PPI prescription or other antiulcer/dyspepsia medication

Overall trial start date

01/03/2012

Overall trial end date

01/10/2017

Reason abandoned

Eligibility

Participant inclusion criteria

1. Males and females more than 60 years of age at the date of screening
2. Subjects who are taking aspirin less than 325mg daily and who have had 4 or more 28 day prescriptions in the last year
3. Subjects who are concurrently using other anti-platelet agents are allowed to enter the study
4. 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)
5. Subjects who are willing to give permission for their paper and electronic medical records to be accessed and abstracted by trial investigators
6. Subjects who are willing to be contacted and interviewed by trial investigators, should the need arise for adverse event assessment, etc
7. 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

Participant type

Patient

Age group

Senior

Gender

Both

Target number of participants

33,000

Participant exclusion criteria

1. Subjects who are currently prescribed anti-ulcer therapy such as H2-receptor antagonists and proton-pump inhibitors
2. Subjects who are currently prescribed oral non-steroidal anti-inflammatory drugs (NSAIDs)
3. Subjects who have a known intolerance or allergy to H. pylori eradication treatment
4. Subjects who are taking drugs with a clinically significant interaction with H. pylori eradication treatment
5. Subjects who are terminally ill or suffer from a life-threatening co-morbidity
6. 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)
7. Subjects currently participating in another interventional clinical trial or who have taken part in a trial in the previous three months

Recruitment start date

01/03/2012

Recruitment end date

01/04/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Nottingham Digestive Diseases Centre
Nottingham
NG7 2UH
United Kingdom

Trial participating centre

University of Southampton
SO17 1BJ

Trial participating centre

Durham University
DH1 3LE

Trial participating centre

University of Oxford
OX1 2JD

Trial participating centre

University of Birmingham
B15 2TT

Trial participating centre

Queens University Belfast
BT7 1NN

Sponsor information

Organisation

University of Nottingham (UK)

Sponsor details

Research Innovation Services
King's Meadow Campus
Lenton Lane
Nottingham
NG7 2NR
United Kingdom

Sponsor type

University/education

Website

http://www.nottingham.ac.uk/

Funders

Funder type

Government

Funder name

Health Technology Assessment Programme (UK) ref: 09/55/52

Alternative name(s)

NIHR Health Technology Assessment Programme, HTA

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

01/12/2017

Participant level data

Not expected to be available

Results - basic reporting

Publication summary

2015 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/26501118

Publication citations

Additional files

Editorial Notes

01/09/2016: the following changes were made to the trial record: 1. The recruitment end date was changed from 01/10/2016 to 01/04/2017. 2. The overall trial end date was changed from 01/04/2017 to 01/10/2017. 25/05/2016: the following changes were made to the trial record: 1. The overall trial end date was changed from 01/03/2016 to 01/04/2017. 2. The target number of participants was changed from 40,000 to 33,000.