A Phase III, Randomized, Study of Aspirin and Esomeprazole Chemoprevention in Barrett's Metaplasia (AspECT)

April 29, 2025 updated by: University of Oxford

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of esomeprazole and aspirin may prevent esophageal cancer in patients with Barrett's metaplasia. It is not yet known whether esomeprazole is more effective with or without aspirin in preventing esophageal cancer in patients with Barrett's metaplasia.

PURPOSE: This randomized phase III trial is studying esomeprazole with or without aspirin to compare how well they work in preventing esophageal cancer in patients with Barrett's metaplasia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES

  • To assess whether intervention with aspirin results in a decreased rate of all causes of mortality or conversion rate from Barrett's metaplasia to adenocarcinoma or high grade dysplasia.
  • To assess whether high dose PPI (protein pump inhibitor) therapy results in a decreased rate of all causes of mortality or conversion rate from Barrett's metaplasia to adenocarcinoma or high grade dysplasia.

SECONDARY OBJECTIVES

  • To assess whether intervention with aspirin results in decreased high-grade dysplasia, in decreased all cause mortality, in decreased oesophageal cancer incidence and in decreased cause-specific mortality when each is considered separately
  • To assess whether intervention with high dose PPI results in decreased high-grade dysplasia, in decreased all cause mortality, in decreased oesophageal cancer incidence and in decreased cause-specific mortality when each is considered separately
  • To assess whether there are clinical and molecular risk factors which can be identified in BM (Barrett's Metaplasia) for the development of BA.
  • To assess the cost effectiveness of aspirin and/or PPI treatment in the prevention of BA.
  • To assess whether intervention with PPI and/or aspirin induces changes in the expression of molecular markers for BA.
  • 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.
  • To assess inherited genetic factors for predisposition to oesophagitis above BM, BM, LGD HGD and BA.
  • To assess what the biological risk factors are for cardiac disease and aspirin resistance.
  • To assess gender differences in outcomes.

Cancer Research UK approved the study in 2003 for a 10 year period to run from 1st January 2005 to 31st December 2014. Funding is renewable annually and is dependent on a satisfactory review by an independent committee.

An application for a funding extension was made to CRUK 18 months before the end of the grant and the funding was extended to 31Aug2018.

A total of 2557 patients have been accrued for this study in the UK.

Study Type

Interventional

Enrollment (Actual)

2557

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

INCLUSION CRITERIA

  1. Aged ≥18 years.
  2. Circumferential Barrett's metaplasia of at least 1cm in length (≥C1M1) or a tongue of Barrett's metaplasia of at least 2cm in length (≥C0M2) (irrespective of the presence now or historically of histologically proven intestinal metaplasia).
  3. Able to give written informed consent.
  4. WHO performance status of 0 or 1 i.e. fully active and self-caring.

EXCLUSION CRITERIA

  1. High grade dysplasia or carcinoma at enrolment.

  2. Medical conditions which would make completing endoscopies or completing the trial difficult including:

    1. Frequent transient ischaemic attacks (3 or more) or severe cerebral vascular accident in the previous 6 months*
    2. Severe respiratory disease with arterial oxygen saturation less 90% at rest
    3. Severe ischaemic heart disease (exercise tolerance less than 100 yards or life expectancy < 4 years) or myocardial infarction in the previous 3 months
    4. Severe inflammatory bowel disease requiring at least one hospital admission of 5 days in the last year or bowels open > 6 times/day * Patients answering yes to criterion a. were eligible for the PPI-only (non-aspirin) arms of the trial
  3. Continuous/frequent non-steroidal anti-inflammatory drug use or COX-2 inhibitors (more than 60 days per year in total).
  4. Patients with absolute contraindications to PPIs, aspirin or their excipients i.e. allergies, ulcers, renal impairment or use of oral anticoagulants.
  5. 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.

If a patient was suitable for inclusion but later becomes unsuitable this should be discussed with the Trial Office before they are withdrawn. Only in exceptional circumstances should patients not be followed up i.e. withdrawal of consent or current life threatening disease with poor outcome and therefore unable to tolerate endoscopy. In these circumstances patients should be followed up in outpatient clinics.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A
20mg Esomeprazole
Drug: Esomeprazole
20mg per day
Other Names:
  • Nexium
Drug: Esomeprazole
80mg per day
Other Names:
  • Nexium
Experimental: Arm B
80mg Esomeprazole
Drug: Esomeprazole
20mg per day
Other Names:
  • Nexium
Drug: Esomeprazole
80mg per day
Other Names:
  • Nexium
Experimental: Arm C
20mg Esomeprazole + 300mg Aspirin
Drug: Esomeprazole
20mg per day
Other Names:
  • Nexium
Drug: Esomeprazole
80mg per day
Other Names:
  • Nexium
Drug: Aspirin
300mg per day
Experimental: Arm D
80mg Esomeprazole + 300mg Aspirin
Drug: Esomeprazole
20mg per day
Other Names:
  • Nexium
Drug: Esomeprazole
80mg per day
Other Names:
  • Nexium
Drug: Aspirin
300mg per day

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
First Event of Death, Oesophageal Adenocarcinoma, High Grade Dysplasia
Time Frame: Events are assessed from the date of randomisation to the end of study which can be patient withdrawal, loss to follow up or study end (8 years or 10 years from randomisation, depending on consent)
Death is recorded on a continuous basis through reporting from trial sites. Oesophageal adenocarcinoma is recorded through endoscopies taken every two years or ad-hoc at clinician decision High Grade Dysplasia is recorded through endoscopies taken every two years or ad-hoc at clinician decision
Events are assessed from the date of randomisation to the end of study which can be patient withdrawal, loss to follow up or study end (8 years or 10 years from randomisation, depending on consent)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
All Cause Mortality
Time Frame: Through study completion, an average of 8.9 years.
Accelerated Failure Time (AFT) analysis comparing time to all cause mortality in low dose PPI (20mg) patients to high dose PPI (80mg) patients and in aspirin patients to non-aspirin patients. Included in AFT model are stratification factors (Barrett's length, age group and presence of baseline intestinal metaplasia) and aspirin randomisation group.
Through study completion, an average of 8.9 years.
Adenocarcinoma Oesophageal Cancer
Time Frame: Assessed every 2 years through study completion, an average of 8.9 years
Number of aspirin and non-aspirin patients and low dose PPI and high dose PPI patients with adenocarcinoma oesophageal cancer
Assessed every 2 years through study completion, an average of 8.9 years
High Grade Dysplasia
Time Frame: High Grade Dysplasia is assessed every two years through study completion, an average of 8.9 years.
Diagnosis of high grade dysplasia is compared in aspirin and non-aspirin trial patients, and in high dose PPI and low dose PPI patients.
High Grade Dysplasia is assessed every two years through study completion, an average of 8.9 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Oxford

Collaborators

AstraZeneca

Investigators

  • Principal Investigator: Janusz Jankowski, MD, National Institute for Health and Care Excellence

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 10, 2005

Primary Completion (Actual)

May 31, 2017

Study Completion (Actual)

May 31, 2017

Study Registration Dates

First Submitted

July 26, 2006

First Submitted That Met QC Criteria

July 26, 2006

First Posted (Estimated)

July 27, 2006

Study Record Updates

Last Update Posted (Actual)

May 1, 2025

Last Update Submitted That Met QC Criteria

April 29, 2025

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000491649
  • OCTO-003 (Other Identifier: Oncology Clinical Trials Office)
  • 2004-003836-77 (EudraCT Number)
  • ISRCTN85156844 (Registry Identifier: ISRCTN)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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