ISRCTN - ISRCTN85156844: Aspirin Esomeprazole Chemoprevention Trial

Plain English Summary

Not provided at time of registration

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 617000
janusz.jankowski@clinpharm.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 amended as of 22/05/2007:
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

To be submitted as of 22/05/2007. The AspECT Trial Office will submit the study protocol and any amendments to a Main Research Ethics Committee in the UK and obtain favourable ethical opinion. The Investigator will submit this protocol, any supporting documentation and any amendments, to a Local Research Ethics Committee or similar body.

As of 04/02/2008 ethics approval information was added to this record as follows:
Ethics approval received from East London and the City Research Ethics Committee 1 (ref: 04/Q0603/1). Amendment reviewed and approved on the 28th September 2007.

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

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

Please note that as of 22/05/2007 the anticipated start and end dates of this trial have been updated as follows:
Anticipated start of recruitment date: 01/03/2005
Anticipated end of recruitment date: 31/03/2009
Anticipated end of follow-up date: 31/10/2018

The previous anticipated end date of this trial was 01/03/2007.

Intervention type

Drug

Phase

Phase III

Drug names

Aspirin, esomeprazole

Primary outcome measures

Primary outcome measures added as of 22/05/2007:
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 amended as of 20/06/2007:
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 amdended as of 22/05/2007:
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 as of 22/05/2007: 5500 (5000 male, 500 female). Target number of participants provided at time of registration: 5000

Participant exclusion criteria

Exclusion criteria amended as of 22/05/2007:
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

31/10/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Oncology Clinical Trials Office (OCTO)
Oxford
OX3 7DQ
United Kingdom

Sponsor information

Organisation

The University of Oxford (UK)

Sponsor details

Research Services
Wellington Square
Oxford
OX1 2JD
United Kingdom
research services@admin.ox.ac.uk