Eosinophilic Esophagitis
Conditions
Keywords
Eosinophilic Esophagitis, Fluticasone, Dysphagia
Brief summary
This was a randomized controlled trial of swallowed fluticasone vs. placebo for eosinophilic esophagitis. Eosinophilic esophagitis is an inflammatory condition in which the wall of the esophagus becomes filled with large numbers of eosinophils, a type of white blood cell. Patients who have this condition have difficulty in swallowing (dysphagia) solid food. Prior to treatment the patients had biopsies of their esophagus and took questionnaires regarding their symptoms. Treatment was given for 6 weeks, after which biopsies were taken from the esophagus to measure any changes in the tissue from before treatment. The primary endpoint was improvement in dysphagia as measured by the validated Mayo Dysphagia Questionaire. Secondary outcomes included partial symptom response, and histologic (tissue) response to treatment.
Detailed description
This was a double-blind randomized placebo controlled trial to evaluate the effect of aerosolized fluticasone therapy on symptomatic dysphagia and histologic eosinophilia in adults newly diagnosed with eosinophilic esophagitis (EoE). Participants were randomized to receive aerosolized swallowed fluticasone 880 mcg bid or placebo inhaler swallowed bid for 6 weeks. Four mid esophageal biopsies were obtained from 10 cm above the squamo-columnar junction; then formalin-fixed and stained with hematoxylin and eosin. All esophageal biopsies were read and scored by a single expert gastrointestinal pathologist. The formalin-fixed paraffin-embedded esophageal biopsies were retrieved and underwent standard major basic protein (MBP) immunofluorescence staining. All special stain slides were then read and scored by another pathologist. 24-hour urine was collected for free cortisol by the standard technique. The original endoscopy was performed before the patient was enrolled in the trial by standard clinical technique. The endoscopy post treatment was done in the clinical research unit by the principal investigator. Patients kept compliance logs that were reviewed at phone interviews at 2 and 4 weeks time and at the end of study evaluation. Ninety percent compliance was required for study inclusion. At the end of 6 weeks, a 24-hour urine cortisol was done, and patients underwent a repeat endoscopy while still on treatment. Mid-esophageal biopsies were obtained and evaluated for eosinophil density and mast cell degranulation. At this visit the patients returned dysphagia and side effects questionnaires.
Interventions
DRUGFluticasone
Aerosolized swallowed fluticasone 880 mg twice a day
DRUGPlacebo
Placebo inhaler swallowed twice a day for 6 weeks
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* \> 20 eosinophils / hpf on biopsies from mid esophagus (hpf = high-powered field) * Abnormal dysphagia questionnaire (question 1a yes, question 1c \> moderate and question 2 \> less than once a week) on Mayo Dysphagia Questionnaire.
Exclusion criteria
* Clinical evidence of infectious process potentially contributing to dysphagia (e.g., candidiasis, cytomegalovirus, herpes) * Systemic or topical steroid therapy for any reason over the past 3 months * Previous steroid treatment for Eosinophilic Esophagitis * Intolerance to steroid therapy in the past * Other cause of dysphagia identified at endoscopy (e.g., reflux esophagitis, stricture, web, ring, achalasia, esophageal neoplasm) * Dilatation of esophagus at time of index endoscopy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Complete Response to Dysphagia | 2 weeks | Measured by the Mayo Dysphagia Questionnaire, a validated 28 item instrument; 0=no dysphagia, higher levels indicate greater dysphagia severity. A complete symptom response was defined as an answer of no to the question In the past 2 weeks, have you had trouble swallowing, not associated with other cold symptoms (such as strep throat or mono)? |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Partial or Complete Response to Dysphagia | 2 weeks | Measured by the Mayo Dysphagia Questionnaire, a validated 28 item instrument; 0=no dysphagia, higher levels indicate greater dysphagia severity. A complete symptom response was defined as an answer of no to the question In the past 2 weeks, have you had trouble swallowing, not associated with other cold symptoms (such as strep throat or mono)? A partial symptom response was defined as an answer of yes to the above question and a decrease in severity of at least 2 levels, or a decrease in frequency of at least 1 level. |
| Number of Participants With Complete Histologic Response | 2 weeks | A complete histologic response was defined as \>90% decrease in mean eosinophil count/high powered field |
Countries
United States
Participant flow
Recruitment details
Adult patients with a new diagnosis of eosinophilic esophagitis were recruited at the Mayo Clinic Rochester between 10/2005 and 12/2009.
Participants by arm
| Arm | Count |
|---|---|
| Fluticasone Aerosolized swallowed fluticasone 880 mcg bid for 6 weeks | 21 |
| Placebo Placebo inhaler swallowed bid for 6 weeks | 21 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Family Issues | 0 | 2 |
| Overall Study | Scheduling | 1 | 2 |
| Overall Study | Travel | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Fluticasone | Placebo | Total |
|---|---|---|---|
| Age Continuous | 37.5 years | 35 years | 37.5 years |
| Food Impaction > 5 minutes Participants with Food Impaction | 16 participants | 17 participants | 33 participants |
| Food Impaction > 5 minutes Participants without Food Impaction | 5 participants | 4 participants | 9 participants |
| Mean Esophageal Eosinophil Count | 40 eosinophils/high powered field | 40 eosinophils/high powered field | 40 eosinophils/high powered field |
| Region of Enrollment United States | 21 participants | 21 participants | 42 participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Male | 18 Participants | 16 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 19 | 6 / 15 |
| serious Total, serious adverse events | 0 / 19 | 0 / 15 |
Outcome results
Primary
Number of Participants With Complete Response to Dysphagia
Measured by the Mayo Dysphagia Questionnaire, a validated 28 item instrument; 0=no dysphagia, higher levels indicate greater dysphagia severity. A complete symptom response was defined as an answer of no to the question In the past 2 weeks, have you had trouble swallowing, not associated with other cold symptoms (such as strep throat or mono)?
Time frame: 2 weeks
Population: Analysis was run per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fluticasone | Number of Participants With Complete Response to Dysphagia | 9 participants |
| Placebo | Number of Participants With Complete Response to Dysphagia | 6 participants |
p-value: 0.74Fisher Exact
Secondary
Number of Participants With Complete Histologic Response
A complete histologic response was defined as \>90% decrease in mean eosinophil count/high powered field
Time frame: 2 weeks
Population: Analysis was run per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fluticasone | Number of Participants With Complete Histologic Response | 13 participants |
| Placebo | Number of Participants With Complete Histologic Response | 0 participants |
p-value: <0.001Fisher Exact
Secondary
Number of Participants With Partial or Complete Response to Dysphagia
Measured by the Mayo Dysphagia Questionnaire, a validated 28 item instrument; 0=no dysphagia, higher levels indicate greater dysphagia severity. A complete symptom response was defined as an answer of no to the question In the past 2 weeks, have you had trouble swallowing, not associated with other cold symptoms (such as strep throat or mono)? A partial symptom response was defined as an answer of yes to the above question and a decrease in severity of at least 2 levels, or a decrease in frequency of at least 1 level.
Time frame: 2 weeks
Population: Analysis was run per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fluticasone | Number of Participants With Partial or Complete Response to Dysphagia | 12 participants |
| Placebo | Number of Participants With Partial or Complete Response to Dysphagia | 7 participants |
p-value: 0.49Fisher Exact