Eosinophilic Esophagitis, Gastroesophageal Reflux Disease
Conditions
Keywords
Gastroesophageal reflux, Proton pump inhibitor, Eosinophilic esophagitis
Brief summary
Background: Up to 40% of patients who are treated with PPIs for symptoms that are thought to be due to GERD experience only incomplete relief of their symptoms. Those patients are deemed PPI failures. Esophageal pH monitoring studies have shown that PPI failure rarely is due to persistent acid reflux. Recently, heartburn that is refractory to treatment with PPIs has been described in patients with eosinophilic esophagitis, a disorder of unknown etiology in which eosinophils infiltrate the squamous epithelium of the esophagus, where they cause symptoms and tissue injury. Presently, it is not clear how often eosinophilic esophagitis underlies PPI failure for patients with GERD symptoms. Purpose: To estimate the frequency with which eosinophilic esophagitis is the cause of PPI failure in patients thought to have heartburn due to GERD. Methods: Patients referred to the Division of Gastroenterology at the Dallas VA Medical Center for the evaluation of heartburn that is refractory to PPI therapy will be invited to participate in the study. Patients who provide informed consent will have a medical history taken. Women of child bearing potential will have a pregnancy test. The patients' current PPI therapy will be discontinued, and patients will be treated with lansoprazole 30 mg BID for one week. The patient will return to the clinic one week later. Patients who feel that their heartburn has not improved by more than 50% from baseline will have an endoscopic evaluation. During the endoscopic examination, biopsy specimens will be taken as follows: A. Two specimens from the proximal esophagus at 20 cm from the incisor teeth. B. Two specimens from the mid-esophagus at 28 cm from the incisor teeth. C. Two specimens from the distal esophagus, 3 cm above the squamo-columnar junction. D. Two specimens from the distal esophagus, 1 cm above the squamo-columnar junction. E. Two specimens from the second portion of the duodenum (to see if the eosinophilia is confined to the esophagus, or part of a more extensive eosinophilic gastroenteritis). A diagnosis of eosinophilic esophagitis will be made if there is at least one high-power field with \>25 eosinophils, or two or more high-power fields with \>15 eosinophils. Potential Benefits: This study will provide an estimate on the frequency with which eosinophilic esophagitis is the cause of PPI failure in patients thought to have heartburn due to GERD. This has substantial potential importance for patient management.
Interventions
DRUGTreat with lansoprazole 30 mg BID for 2 weeks, endoscopic examination with esophageal biopsy for patients with persistent symptoms
Treat with lansoprazole 30 mg BID for 2 weeks, perform endoscopic examination with esophageal biopsy
Sponsors
TAP Pharmaceutical Products Inc.
Dallas VA Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Male and female patients ages 18 years and older who are referred to the Division of Gastroenterology at the Dallas VA Medical Center for the evaluation of heartburn that is refractory to PPI therapy
Exclusion criteria
1. Patients unwilling or unable to provide informed consent. 2. Allergy to lansoprazole. 3. Patients taking warfarin. 4. Coagulopathy that precludes safe biopsy of the esophagus. 5. Comorbidity that precludes safe participation in the study. 6. Pregnancy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Eosinophilic Esophagitis | 8 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Had Resolution of Heartburn With Lansoprazole | After 8 weeks of treatment | Resolution of heartburn defined as \>50% improvement in symptoms |
Countries
United States
Participant flow
Recruitment details
Consecutive patients referred to a general GI clinic at our VA hospital for the evaluation of PPI-resistant heartburn were invited to participate.
Pre-assignment details
102 patients agreed to participate. For 10 patients the symptom described was not consistent with heartburn and another 27 described heartburn that was not refractory to therapy. 65 patient had PPI-resistant heartburn; 33 were taking PPI incorrectly; 11 taking insufficient dose of omeprazole.
Participants by arm
| Arm | Count |
|---|---|
| Patients Whose PPI Was Changed to Lansoprazole In 21 patients taking omeprazole ≥80 mg/day, the PPI was changed to lansoprazole 30 mg BID before breakfast and dinner. | 21 |
| Total | 21 |
Baseline characteristics
| Characteristic | Patients Whose PPI Was Changed to Lansoprazole |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants |
| Region of Enrollment United States | 21 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 21 |
| serious Total, serious adverse events | 0 / 21 |
Outcome results
Primary
Number of Participants With Eosinophilic Esophagitis
Time frame: 8 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients Whose PPI Was Changed to Lansoprazole | Number of Participants With Eosinophilic Esophagitis | 0 participants |
Secondary
Number of Patients Who Had Resolution of Heartburn With Lansoprazole
Resolution of heartburn defined as \>50% improvement in symptoms
Time frame: After 8 weeks of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients Whose PPI Was Changed to Lansoprazole | Number of Patients Who Had Resolution of Heartburn With Lansoprazole | 9 participants |