Condition category
Digestive System
Date applied
17/01/2005
Date assigned
15/02/2005
Last edited
24/08/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://aspect.octru.ox.ac.uk

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 Barrett’s metaplasia to adenocarcinoma or high grade dysplasia
2. To assess whether high dose PPI therapy decreases the mortality or conversion rate from Barrett’s 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 Barrett’s metaplasia to adenocarcinoma or high grade dysplasia
2. To assess whether high dose PPI therapy decreases the mortality or conversion rate from Barrett’s 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, 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 measures

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, measured 2 yearly

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
2. Conversion to oesophageal adenocarcinoma
3. Conversion to high grade dysplasia
4. Death from oesophageal cancer
5. Cost/oesophageal adenocarcinoma prevented
6. Cost/quality adjusted life year saved
7. Molecular markers to be identified at the end of the trial

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

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. Patient’s able to give written consent
4. Patient’s 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 Barrett’s Metaplasia at least 1 cm long, and histologically proven intestinal metaplasia in at least one sample
3. Patient’s able to give written consent
4. Patient’s 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. Patient’s 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

Sponsor information

Organisation

University of Oxford (UK)

Sponsor details

Clinical Trials and Research Governance
Joint Research Office
Block 60
Churchill Hospital
Oxford
OX3 7LE
United Kingdom

Sponsor type

University/education

Website

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.

Intention to publish date

31/10/2018

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

24/08/2016: the target number of participants was changed from "5500 (5000 male, 500 female)" to “Target number of participants at end of recruitment (Feb 2009): 2,500. Final recruitment: 2,513”. 22/05/2007: the target number of participants was changed from "5000" to "5500 (5000 male, 500 female)".