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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
University of Oxford
ClinicalTrials.gov Identifier:
NCT00357682
First received: July 26, 2006
Last updated: February 21, 2012
Last verified: February 2012
  Purpose

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.


Condition Intervention Phase
Esophageal Cancer
Precancerous Condition
Drug: Esomeprazole
Drug: Aspirin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase III, Randomized, Study of Aspirin and Esomeprazole Chemoprevention in Barrett's Metaplasia

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • Conversion of Barrett's esophagus to adenocarcinoma of the esophagus or high-grade dysplasia [ Time Frame: assessed every 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • All causes of mortality [ Time Frame: assessed annually ] [ Designated as safety issue: No ]

Enrollment: 2513
Study Start Date: March 2005
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
20mg Esomeprazole
Drug: Esomeprazole
20mg per day
Experimental: Arm B
80mg Esomeprazole
Drug: Esomeprazole
80mg per day
Experimental: Arm C
20mg Esomeprazole + 300mg Aspirin
Drug: Esomeprazole
20mg per day
Drug: Aspirin
300mg per day
Experimental: Arm D
80mg Esomeprazole + 300mg Aspirin
Drug: Esomeprazole
80mg per day
Drug: Aspirin
300mg per day

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 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 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 will be made to CRUK 18 months before the end of the current grant.

A total of 2513 patients have been accrued for this study. They remain on trial medication and follow up.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00357682

Sponsors and Collaborators
University of Oxford
AstraZeneca
Investigators
Principal Investigator: Janusz Jankowski, MD Queen Mary University of London
  More Information

No publications provided

Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT00357682     History of Changes
Other Study ID Numbers: CDR0000491649, OCTO-003, EUDRACT-2004-003836-77, ISRCTN85156844, EU-20628
Study First Received: July 26, 2006
Last Updated: February 21, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Oxford:
esophageal cancer
Barrett's esophagus

Additional relevant MeSH terms:
Barrett Esophagus
Esophageal Neoplasms
Metaplasia
Precancerous Conditions
Digestive System Abnormalities
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Pathologic Processes
Aspirin
Esomeprazole
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on August 20, 2014