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

Phase 3

Completed

• Conditions: Esophageal Cancer; Precancerous Condition
• Interventions: Drug: Esomeprazole; Drug: Aspirin

• Registration Number: NCT00357682
• Lead Sponsor: University of Oxford

Brief Summary

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.

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 Timeline

• Study Start: 2005-03-10
• Study First Submitted: 2006-07-26
• Study First Submitted QC: 2006-07-26
• Study First Posted: 2006-07-27
• Primary Completion: 2017-05-31
• Study Completion: 2017-05-31
• Status Verified: 2018-08
• Results First Submitted: 2018-11-06
• Results First Submitted QC: 2025-04-29
• Last Update Submitted: 2025-04-29
• Results First Posted: 2025-05-01
• Last Update Posted: 2025-05-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2557

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Arm A	Esomeprazole	20mg Esomeprazole
Arm B	Esomeprazole	80mg Esomeprazole
Arm C	Aspirin	20mg Esomeprazole + 300mg Aspirin
Arm C	Esomeprazole	20mg Esomeprazole + 300mg Aspirin
Arm D	Esomeprazole	80mg Esomeprazole + 300mg Aspirin
Arm D	Aspirin	80mg Esomeprazole + 300mg Aspirin

Primary Outcome Measures

Name	Time	Method
First Event of Death, Oesophageal Adenocarcinoma, High Grade Dysplasia	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

Secondary Outcome Measures

Name	Time	Method
All Cause Mortality	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.
Adenocarcinoma Oesophageal Cancer	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
High Grade Dysplasia	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.