Randomized, Double-Blinded Phase II Trial of Esomeprazole Versus Esomeprazole + Two Doses of Aspirin in Barrett's Esophagus Patients
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 122
- Locations
- 1
- Primary Endpoint
- Change in Mean Tissue Prostaglandin E2 (PGE2) Concentration as Determined From Barrett's Research Mucosal Biopsy Samples
Study Overview
Brief Summary
This randomized phase II trial is studying the effect of esomeprazole magnesium and aspirin on tissue PGE2 levels compared with esomeprazole and placebo. This type of chemoprevention treatment investigates the use of certain drugs to assess whether they assist in the prevention of cancer. The use of esomeprazole magnesium with or without aspirin may help prevent esophageal cancer in patients with Barrett esophagus.
Detailed Description
PRIMARY OBJECTIVES:
I. To assess the effects of a 28 day intervention with aspirin 81 mg placebo orally (PO) once daily (QD) + aspirin 325 mg placebo PO QD + esomeprazole 40 mg PO BID versus aspirin 81 mg PO QD + aspirin 325 mg placebo PO QD + esomeprazole 40 mg PO BID versus aspirin 325 mg PO QD + aspirin 81 mg placebo PO QD + esomeprazole 40 mg PO BID on the absolute change in tissue prostaglandin E2 (PGE2) concentration, as determined from Barrett's esophagus mucosal biopsy samples obtained pre- and post-intervention (i.e. two pair-wise comparisons of two different doses of active aspirin regimens versus aspirin placebo group), Specifically, the two active aspirin + esomeprazole arms will be independently analyzed to see if they significantly reduce the mean tissue PGE2 concentration from Pre- to Post-intervention as compared to the aspirin placebo + esomeprazole arm.
SECONDARY OBJECTIVES:
I. To determine if the change in the tissue PGE2 concentration decreases significantly in the aspirin placebo + esomeprazole arm.
II. To compare the change in mean tissue PGE2 concentration between the two active intervention arms to determine which one appears the most promising for further testing.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically confirmed Barrett esophagus, meeting all of the following criteria:
- •Presence of specialized columnar epithelium anywhere in the tubular esophagus with ≥ 2 cm of circumferential involvement
- •No evidence of high-grade dysplasia or cancer by esophagogastroduodenoscopy (EGD)
- •No prior histologically confirmed esophageal dysplasia, including cancer
- •Adequate Barrett mucosa, defined as ≥ 4 of 8 research samples with≥ 50% intestinal metaplasia in research biopsies
- •No ulcer, erosion, plaque, nodule, stricture, or other luminal irregularity within the Barrett's segment or erosive esophagitis (Los Angeles classification > grade A) detected at pre-intervention EGD exam
- •Eastern Cooperative Group (ECOG) performance status 0-2
- •Hemoglobin normal
- •Platelet count ≥ 100,000/mm³
- •Aspartate aminotransferase (AST) ≤ 2.5 times upper limit of normal (ULN)
- •Alkaline phosphatase ≤ 2.5 times ULN
- •Bilirubin ≤ 2.5 times ULN
- •Creatinine ≤ 2.5 times ULN
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No nasal polyps associated with asthma or induced or exacerbated by aspirin
- •No malignancy within the past 5 years except for nonmelanoma skin cancer
- •No history of allergic reactions attributed to compounds of similar chemical or biologic composition to the study agents or rescue medication
- •No history of endoscopically or radiographically diagnosed peptic ulcer disease (bleeding or nonbleeding)
- •No other uncontrolled illness including, but not limited to, any of the following:
- •Ongoing or active infection
- •Symptomatic congestive heart failure
- •Unstable angina pectoris
- •Cardiac arrhythmia
- •Bleeding disorder
- •Vitamin K deficiency
- •Alcohol abuse (defined as ingestion of ≥ 3 drinks per day)
- •Psychiatric illness or social situations that would limit study compliance
- •At least 3 months since prior chronic use (defined as ≥ 7 days during the 3 months preceding the beginning of the Run-in phase) of acetylsalicylic acid (aspirin), nonsteroidal antiinflammatory drug (NSAIDs), or selective cyclooxygenase (COX-2) inhibitors
- •At least 3 months since prior investigational agents except innocuous agents with no known interaction with the study agents (e.g., standard dose multivitamins or topical agents for limited skin conditions)
- •No prior fundoplication, bariatric surgery, or any other major upper gastrointestinal surgery
- •Prior cholecystectomy allowed
- •No other concurrent NSAIDs (including aspirin) or selective COX-2 inhibitor therapy
- •No concurrent anticoagulant drugs including, but not limited to, any of the following:
- •Low-molecular weight heparin
- •Clopidogrel bisulfate
- •Extended-release dipyridamole
Exclusion Criteria
- Not provided
Arms & Interventions
Arm I (placebo, esomeprazole magnesium)
Patients receive two oral placebos once daily and oral esomeprazole magnesium (40 mg, twice daily).
Intervention: esomeprazole magnesium (Drug)
Arm I (placebo, esomeprazole magnesium)
Patients receive two oral placebos once daily and oral esomeprazole magnesium (40 mg, twice daily).
Intervention: placebo (Other)
Arm II (low-dose aspirin, esomeprazole magnesium)
Patients receive both an oral placebo and acetylsalicylic acid (81 mg dose), once daily and oral esomeprazole magnesium (40 mg, twice daily).
Intervention: acetylsalicylic acid (Drug)
Arm II (low-dose aspirin, esomeprazole magnesium)
Patients receive both an oral placebo and acetylsalicylic acid (81 mg dose), once daily and oral esomeprazole magnesium (40 mg, twice daily).
Intervention: esomeprazole magnesium (Drug)
Arm II (low-dose aspirin, esomeprazole magnesium)
Patients receive both an oral placebo and acetylsalicylic acid (81 mg dose), once daily and oral esomeprazole magnesium (40 mg, twice daily).
Intervention: placebo (Other)
Arm III (higher-dose aspirin, esomeprazole magnesium)
Patients receive both an oral placebo and acetylsalicylic acid (325 mg dose), once daily and oral esomeprazole magnesium (40 mg, twice daily).
Intervention: acetylsalicylic acid (Drug)
Arm III (higher-dose aspirin, esomeprazole magnesium)
Patients receive both an oral placebo and acetylsalicylic acid (325 mg dose), once daily and oral esomeprazole magnesium (40 mg, twice daily).
Intervention: esomeprazole magnesium (Drug)
Arm III (higher-dose aspirin, esomeprazole magnesium)
Patients receive both an oral placebo and acetylsalicylic acid (325 mg dose), once daily and oral esomeprazole magnesium (40 mg, twice daily).
Intervention: placebo (Other)
Outcomes
Primary Outcomes
Change in Mean Tissue Prostaglandin E2 (PGE2) Concentration as Determined From Barrett's Research Mucosal Biopsy Samples
Time Frame: Baseline to 30 days after completion of study treatment
The mean tissue PGE2 is reported for each Arm.
Secondary Outcomes
- Toxicity(Up to 30 days after completion of study treatment)