Plain English Summary
Background and study aims
Barrett's oesophagus is a condition where the cells that line the lower part of the (oesophagus) (gullet) are damaged by acid and bile travelling upwards from the stomach. Patients with Barrett’s oesophagus have an increased risk of developing oesophageal cancer. This study uses two drugs with the aim of reducing the risk of progression of Barrett’s oesophagus to oesophageal cancer. All participants receive a drug called a proton pump inhibitor which reduces stomach acidity and may stop the cells in the oesophagus from being damaged more and becoming cancerous. Some participants also receive aspirin because there is some evidence that aspirin reduces the risk of developing oesophageal, stomach and colon cancer.
Who can participate?
Patients aged over 18 with Barrett's oesophagus
What does the study involve?
Participants are randomly allocated to one of four groups to take one of two doses of the proton pump inhibitor either with or without aspirin. Participants take tablets every day for at least 8 years and have annual follow up visits either at the hospital or by telephone. Participants also have endoscopies every 2 years which are the same as the standard monitoring endoscopies for patients with Barrett’s oesophagus, although some additional samples are taken for the study.
What are the possible benefits and risks of participating?
Participants have regular follow up visits and endoscopies and receive their study tablets free of charge. The benefit of the drugs in preventing the progression of Barrett’s oesophagus to oesophageal cancer will not be known until after the end of the study. Both of the study drugs have potential side effects but generally patients tolerate the treatment well. There are small risks to having an endoscopy but there is no greater risk to having an endoscopy in this study than there is to having an endoscopy as part of standard Barrett’s monitoring.
Where is the study run from?
University of Oxford (UK) and 85 hospitals listed at https://aspect.octru.ox.ac.uk/all-sites-3
When is the study starting and how long is it expected to run for?
March 2005 to October 2018
Who is funding the study?
Cancer Research UK (CRUK) (UK)
Who is the main contact?
Prof. Janusz Jankowski
octo-aspect@oncology.ox.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Prof Janusz Jankowski
ORCID ID
Contact details
Oncology Clinical Trials Office (OCTO)
Department of Clinical Pharmacology
Old Road Campus Research Building
University of Oxford
Old Road Campus
Off Roosevelt Drive
Headington
Oxford
OX3 7DQ
United Kingdom
+44 (0)1865 617011
octo-aspect@oncology.ox.ac.uk
Additional identifiers
EudraCT number
2004-003836-77
ClinicalTrials.gov number
NCT00357682
Protocol/serial number
N/A
Study information
Scientific title
A phase III, randomised, study of Aspirin and Esomeprazole Chemoprevention in Barrett's Metaplasia (BM)
Acronym
AspECT
Study hypothesis
Study objectives as of 24/08/2016:
Primary objectives:
1. To assess whether intervention with aspirin result in a decreased mortality or conversion rate from Barretts metaplasia to adenocarcinoma or high grade dysplasia
2. To assess whether high dose PPI therapy decreases the mortality or conversion rate from Barretts Metaplasia to adenocarcinoma or high grade dysplasia
Secondary objectives:
1. To assess whether there are there clinical and molecular risk factors than can be identified in BM for the development of BA
2. To assess the cost effectiveness of aspirin and/or PPI treatment in the prevention of BA.
3. To assess whether intervention with PPI and/or aspirin induces changes in the expression of molecular markers for BA
4. To assess how quality of life is affected by the different treatments
5. To assess what the biological risk factors are for cardiac disease and aspirin resistance
6. To assess gender differences in outcomes
Tertiary/exploratory objectives:
1. To assess aspirin’s role on the development of colorectal adenomas and cancer
2. To collect and bank samples for use in future ethically approved studies
Study objectives from 22/05/2007 to 24/08/2016:
Primary objectives:
1. To assess whether intervention with aspirin result in a decreased mortality or conversion rate from Barretts metaplasia to adenocarcinoma or high grade dysplasia
2. To assess whether high dose PPI therapy decreases the mortality or conversion rate from Barretts Metaplasia to adenocarcinoma or high grade dysplasia
Secondary objectives:
1. To assess whether there are there clinical and molecular risk factors than can be identified in BM for the development of BA
2. To assess the cost effectiveness of aspirin and/or PPI treatment in the prevention of BA.
3. To assess whether intervention with PPI and/or aspirin induces changes in the expression of molecular markers for BA
4. To assess whether molecular markers can be used to monitor disease and identify groups at high risk of conversion
5. To investigate new genes important in the progression of BA, as a unique tissue bank will be available with a complete endoscopic, histological, physiology and pharmaceutical history
6. To investigate host susceptibility genes and environmental (diet) versus gene interactions
7. To investigate how intervention with PPI and/or aspirin influences the timing and severity of acid reflux into the oesophagus and the change in concentrations of bile acids in the oesophageal aspirates
Study hypothesis provided at time of registration:
The aim of this trial is to see if high or low dose esomeprazole alone, or esomeprazole and aspirin together can help stop Barrett's oesophagus developing into oesophageal cancer.
Ethics approval
East London and the City Research Ethics Committee 1, 08/06/2004, ref: 04/Q0603/1
Study design
Phase III multi-centre randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet
Condition
Barrett's oesophagus due to chronic reflux in the gullet
Intervention
Please note that the doses of the drugs below were added as of 22/05/2007:
Arm A (Standard Therapy): 20 mg esomeprazole
Arm B (Strong Acid Suppression): 80 mg esomeprazole
Arm C (Standard Therapy + Aspirin): 20 mg esomeprazole + 300 mg aspirin
Arm D (Strong Acid Suppression + Aspirin): 80 mg esomeprazole + 300 mg aspirin
Intervention type
Drug
Phase
Phase III
Drug names
Aspirin, esomeprazole
Primary outcome measure
Primary outcome measures as of 24/08/2016:
A composite primary endpoint of all-cause mortality and conversion to adenocarcinoma and conversion to high grade dysplasia, assessed after all patients have completed at least 8 years of follow up
Primary outcome measures from 22/05/2007 to 24/08/2016:
The following will be assessed at 4 and 8 years and four yearly until the end of study:
1. Conversion to adenocarcinoma of the oesophagus
2. Conversion to high grade dysplasia
3. Death by all causes
Secondary outcome measures
Secondary outcome measures as of 24/08/2016:
1. All-cause mortality, assessed after all patients have completed at least 8 years of follow up
2. Conversion to oesophageal adenocarcinoma, assessed after all patients have completed at least 8 years of follow up
3. Conversion to high grade dysplasia, assessed after all patients have completed at least 8 years of follow up
4. Death from oesophageal cancer, assessed after all patients have completed at least 8 years of follow up
5. Cost/oesophageal adenocarcinoma prevented, assessed after all patients have completed at least 8 years of follow up
6. Cost/quality adjusted life year saved, assessed after all patients have completed at least 8 years of follow up
7. Molecular markers to be identified at the end of the trial, assessed after the end of the trial following sample analysis
Secondary outcome measures from 20/06/2007 to 24/08/2016:
The following will be assessed at 4 and 8 years and four yearly until the end of study:
1. Incidence of oesophagectomy
2. Stage of adenocarcinoma
3. Incidence of ablation therapy
4. Incidence of endoscopic mucosal resection
5. Quality of life, assessed by The Reflux Disease Questionnaire and the Euroqol-5 Dimensions (EQ-5D) Questionnaire
6. Molecular endpoints including genotype and mutational status
Secondary outcome measures added as of 22/05/2007:
1. Oesophagectomy
2. Stage of adenocarcinoma
3. Ablation therapy
4. Endoscopic mucosal resection
Overall trial start date
01/03/2005
Overall trial end date
31/10/2018
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Inclusion criteria as of 24/08/2016:
1. Patients aged over 18 years
2. Circumferential Barrett’s metaplasia of at least 1 cm in length (≥C1M1) or a tongue of Barrett’s metaplasia of at least 2 cm in length (≥C0M2) (irrespective of the presence now or historically of histologically proven intestinal metaplasia)
3. Patients able to give written consent
4. Patients with World Health Organization (WHO) activity profile of 0 or 1 i.e. fully active and self-caring
Inclusion criteria from 22/05/2007 to 24/08/2016:
1. Patients aged over 18 years
2. Patient with circumferential Barretts Metaplasia at least 1 cm long, and histologically proven intestinal metaplasia in at least one sample
3. Patients able to give written consent
4. Patients with World Health Organization (WHO) activity profile of 0 or 1 i.e. fully active and self-caring
Inclusion criteria provided at time of registration:
1. Male between 40 - 75 years
2. At least 2 cm from the gastro-oesophageal junction of circumferential BM (histologically proven by intestinal metaplasia in at least one sample)
3. Able to give written consent
4. World Health Organization (WHO) activity profile of 0 i.e. fully active and self-caring
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Target number of participants at end of recruitment (Feb 2009): 2,500. Final recruitment: 2,513
Participant exclusion criteria
Exclusion criteria as of 24/08/2016:
1. Patients with high grade dysplasia or carcinoma at enrolment
2. Medical conditions which would make completing endoscopies or completing the trial difficult, including:
2.1. Frequent transient ischaemic attacks (3 or more) or severe cerebral vascular accident in the previous 6 months (patients answering yes were eligible for the PPI-only (non-aspirin) arms of the trial)
2.2. Severe respiratory disease with arterial oxygen saturation of less than 90% at rest
2.3. Severe ischaemic heart disease (exercise tolerance less than 100 yards or life expectancy < 4 years) or myocardial infarction in the previous 3 months
2.4. Severe inflammatory bowel disease requiring at least one hospital admission of 5 days in the last year or bowels open > 6 times/day
3. Patients with absolute contraindications to PPIs, aspirin or their excipients i.e. allergies, ulcers, renal impairment or use of oral anticoagulants.
4. Pregnant or lactating women will not undergo endoscopy and may be given dispensation to stop drug therapy for a year. This should be discussed with the Trial Office.
Exclusion criteria from 22/05/2007 to 24/08/2016:
1. Patients with high grade dysplasia or carcinoma at enrolment;
2. Patients with medical conditions which would make completing endoscopies or the trial difficult to complete including:
2.1. Previous transient ischaemic attacks or cerebral vascular disease
2.2. Severe respiratory disease
2.3. Severe ischaemic heart disease or myocardial infarction in the previous 6 months
2.4. Inflammatory bowel disease
3. Patients who are on continuous aspirin or non-steroidal anti-inflammatories or Cox-2 inhibitors (more than 3 courses/year)
4. Patients with absolute contraindications to PPIs, aspirin or their excipients such as allergies, ulcers, renal impairment or use of oral anticoagulants
5. Pregnant or lactating women
Exclusion criteria provided at time of registration:
1. High grade dysplasia or carcinoma at enrolment
2. Medical conditions which would make endoscopy or the trial difficult or failure to complete including transient ischaemic attacks or cerebral vascular disease, severe respiratory disease, severe ischaemic heart disease or recent myocardial infarction or inflammatory bowel disease
3. Patients who are on continuous aspirin or non-steroidal drugs (more than 3 courses/year)
4. Absolute contraindications (ulcers) or allergies to PPIs or aspirin such as renal impairment and oral anticoagulants
Recruitment start date
01/03/2005
Recruitment end date
28/02/2009
Locations
Countries of recruitment
United Kingdom
Trial participating centre
University of Oxford
Oxford
OX3 7DQ
United Kingdom
Trial participating centre
85 active sites
-
United Kingdom
Funders
Funder type
Charity
Funder name
Cancer Research UK (CRUK) (UK)
Alternative name(s)
CRUK
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Results and Publications
Publication and dissemination plan
The intention is to publish this research in a specialist peer-reviewed scientific journal on completion of the study. The results will also be presented at scientific meetings. The AspECT Chief Investigator and Trial Management Group will be involved in reviewing drafts of the manuscripts, abstracts, press releases and any other publications arising from the trial.
IPD sharing statement
The datasets generated during and/or analysed during the current study are/will be available upon request from Janusz Jankowski (Chief Investigator) (jjankowski@uclan.ac.uk) and Sharon Love (Statistician) (Sharon.Love@csm.ox.ac.uk). The TMG assess applications for the data and the DSMC give permission for distribution of the data. All data may be made available after the study’s laboratory endpoints have been completed.
Intention to publish date
31/10/2018
Participant level data
Available on request
Basic results (scientific)
Publication list
2018 results in: https://www.ncbi.nlm.nih.gov/pubmed/30057104