A Study of Flovent in Patients With Eosinophilic Esophagitis
Study Details
Study Description
Brief Summary
The purpose of this study is to test the effects (both good and bad) of high dose swallowed fluticasone propionate (Flovent) in subjects with eosinophilic esophagitis (EoE).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Flovent 1760 mcg Fluticasone propionate 880 mcg twice daily for 3 months |
Drug: Flovent
1760 mcg daily
Other Names:
|
| Placebo Comparator: Placebo Placebo twice daily for 3 months |
Other: Placebo
Placebo
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Who Attained Remission. [3 months]
Remission is considered achieved when the highest eosinophil count per high power field (hpf) in all esophageal biopsies is </= 1 eosinophil/hpf after 3 months of therapy.
Secondary Outcome Measures
- Percent of Participants With Decreased Cortisol Levels After 3 Months [3 months]
Blood and saliva cortisol was measured and compared to reference range at 3 months. Participants with measures below the reference range were considered "decreased".
- Association of Subject Age, Body Mass Index Z-score, and Allergic Status to Response to Flovent [3 months]
Strength of the association (odds ratio) of age, body mass index (BMI) z-score , and allergic status with response to Flovent. Allergic status is defined as a history of allergic disease (allergic rhinitis, hay fever, atopic dermatitis, eczema, food anaphylaxis, asthma, or positive skin prick tests). Response is defined as <= 1 eosinophil/high power field in esophageal biopsies.
- EoE Score After 3 Months [3 months]
The gene expression profile is associated with an EoE score algorithm reflecting disease status and severity in a quantifiable number - called the EoE score, based on a core set of 77 diagnostic genes. The EoE score was calculated for Flovent responders and placebo. Higher scores indicate normalization of genes associated with inflammation and fibrosis (disease severity). Therefore higher scores mean a better outcome. The minimum score is zero. There is no maximum score.
- Association of Compliance With Therapy and Response to Flovent [3 months]
Odds ratio was determined to show the strength of the association between compliance with the drug therapy and response to the drug therapy
- Percent of Participants With Abdominal Pain After Therapy [3 months]
Percent of participants responding that they experienced abdominal pain (i.e. they did not respond "never") after therapy. Responses were dichotomized into "Never" and "sometimes".
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Signed informed consent for study by subject, or parent/guardian if subject is a minor. Assent will be obtained from all minors 11 years of age and older.
-
Histological findings on esophageal biopsy to include peak eosinophil density ≥ 24 per high power field (400x) in the proximal or distal esophagus validated by a pathologist at CCHMC.
-
Allergy evaluation including skin-prick testing with multiple food antigens to ensure elimination diet is not indicated.
-
Have undergone a minimum 3 months of elimination diet as indicated by skin-prick testing without detectable resolution by repeat endoscopy with biopsies demonstrating persistent EE OR subject/parental refusal to follow elimination diet. If the subject/parent refuses the elimination diet, they are eligible for this study.
-
Treatment with a proton-pump inhibitor for at least two months (rounded to nearest month) prior to endoscopy OR failure of histological improvement as defined by < 1 eosinophil per HPF after 2 month (rounded to nearest month) trial of proton pump inhibitor documented by prior endoscopy. The PPI must be used prior to endoscopy to rule out the possibility of GERD.
Exclusion Criteria:
-
History of poor tolerance to Fluticasone Propionate (FP), as defined as multiple episodes of oral candidiasis, hypothalamic-pituitary-adrenal axis suppression as evidenced by signs of Cushing syndrome, headaches, or increased respiratory infections during exposure to Flovent
-
Unable to cooperate with use of MDI
-
Pregnant females
-
Concurrent or recent (within 3 months) use of systemic corticosteroids.
-
Unable to swallow medicines (i.e., fed only by gastrostomy tube).
-
Comorbid eosinophilic disorders.
-
Previously treated with swallowed glucocorticoid for EE within 3 months of the screening visit. Nasal glucocorticoids taken for EE are permitted.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Children's Hospital of Denver | Aurora | Colorado | United States | 80045 |
| 2 | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | United States | 45229 |
| 3 | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | United States | 19104 |
| 4 | University of Utah | Salt Lake City | Utah | United States | 84132 |
Sponsors and Collaborators
- Marc Rothenberg, MD
Investigators
- Principal Investigator: Marc E. Rothenberg, M.D., Ph.D., Children's Hospital Medical Center, Cincinnati
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 06-10-07
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Flovent 1760 mcg | Placebo |
|---|---|---|
| Arm/Group Description | Drug Flovent : 1760 mcg daily | Placebo twice daily |
| Period Title: Overall Study | ||
| STARTED | 28 | 14 |
| COMPLETED | 23 | 13 |
| NOT COMPLETED | 5 | 1 |
Baseline Characteristics
| Arm/Group Title | Flovent 1760 mcg | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Drug Flovent : 880 mcg twice daily | Placebo twice daily | Total of all reporting groups |
| Overall Participants | 28 | 14 | 42 |
| Age (Count of Participants) | |||
| <=18 years |
26
92.9%
|
12
85.7%
|
38
90.5%
|
| Between 18 and 65 years |
2
7.1%
|
2
14.3%
|
4
9.5%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
12.15
(6.42)
|
13.54
(7.11)
|
12.6
(6.6)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
6
21.4%
|
1
7.1%
|
7
16.7%
|
| Male |
22
78.6%
|
13
92.9%
|
35
83.3%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
28
100%
|
14
100%
|
42
100%
|
Outcome Measures
| Title | Percentage of Participants Who Attained Remission. |
|---|---|
| Description | Remission is considered achieved when the highest eosinophil count per high power field (hpf) in all esophageal biopsies is </= 1 eosinophil/hpf after 3 months of therapy. |
| Time Frame | 3 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Flovent 1760 mcg | Placebo |
|---|---|---|
| Arm/Group Description | Drug Flovent : 880 mcg twice daily | Placebo twice daily |
| Measure Participants | 23 | 13 |
| Number (95% Confidence Interval) [percentage of participants] |
65.2
232.9%
|
0
0%
|
| Title | Percent of Participants With Decreased Cortisol Levels After 3 Months |
|---|---|
| Description | Blood and saliva cortisol was measured and compared to reference range at 3 months. Participants with measures below the reference range were considered "decreased". |
| Time Frame | 3 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Flovent 1760 mcg | Placebo |
|---|---|---|
| Arm/Group Description | Fluticasone propionate 880 mcg twice daily for 3 months Flovent: 1760 mcg daily | Placebo twice daily |
| Measure Participants | 23 | 13 |
| Number [percentage of participants] |
17.4
62.1%
|
0
0%
|
| Title | Association of Subject Age, Body Mass Index Z-score, and Allergic Status to Response to Flovent |
|---|---|
| Description | Strength of the association (odds ratio) of age, body mass index (BMI) z-score , and allergic status with response to Flovent. Allergic status is defined as a history of allergic disease (allergic rhinitis, hay fever, atopic dermatitis, eczema, food anaphylaxis, asthma, or positive skin prick tests). Response is defined as <= 1 eosinophil/high power field in esophageal biopsies. |
| Time Frame | 3 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population is restricted only to those that were given Flovent for the purpose of determining whether these specific variables are associated with response to drug |
| Arm/Group Title | Flovent 1760 mcg |
|---|---|
| Arm/Group Description | Drug Flovent : 1760 mcg daily |
| Measure Participants | 23 |
| Odds Ratio for Age |
0.907
|
| Odds Ratio for BMI Z-Score |
0.541
|
| Odds Ratio for Allergic Status |
0.572
|
| Title | EoE Score After 3 Months |
|---|---|
| Description | The gene expression profile is associated with an EoE score algorithm reflecting disease status and severity in a quantifiable number - called the EoE score, based on a core set of 77 diagnostic genes. The EoE score was calculated for Flovent responders and placebo. Higher scores indicate normalization of genes associated with inflammation and fibrosis (disease severity). Therefore higher scores mean a better outcome. The minimum score is zero. There is no maximum score. |
| Time Frame | 3 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Population includes only responders to Flovent and all participants finishing the study on Placebo. |
| Arm/Group Title | Flovent 1760 mcg Responders | Placebo |
|---|---|---|
| Arm/Group Description | Drug Flovent : 1760 mcg daily | Placebo twice daily |
| Measure Participants | 15 | 13 |
| Mean (Standard Deviation) [score on a scale] |
382
(47)
|
152
(119)
|
| Title | Association of Compliance With Therapy and Response to Flovent |
|---|---|
| Description | Odds ratio was determined to show the strength of the association between compliance with the drug therapy and response to the drug therapy |
| Time Frame | 3 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population is restricted only to those that were given Flovent for the purpose of determining whether compliance with therapy was associated with response to drug |
| Arm/Group Title | Flovent 1760 mcg |
|---|---|
| Arm/Group Description | Drug Flovent : 1760 mcg daily |
| Measure Participants | 23 |
| Number (95% Confidence Interval) [Odds Ratio] |
1.037
|
| Title | Percent of Participants With Abdominal Pain After Therapy |
|---|---|
| Description | Percent of participants responding that they experienced abdominal pain (i.e. they did not respond "never") after therapy. Responses were dichotomized into "Never" and "sometimes". |
| Time Frame | 3 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Flovent 1760 mcg | Placebo |
|---|---|---|
| Arm/Group Description | Drug Flovent : 1760 mcg daily | Placebo |
| Measure Participants | 23 | 12 |
| Number [percentage of participants] |
63
225%
|
50
357.1%
|
Adverse Events
| Time Frame | From consent to cessation of treatment which was approximately 4 months | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse events were reported according to the MedDRA System Organ Class | |||
| Arm/Group Title | Flovent 1760 mcg | Placebo | ||
| Arm/Group Description | Drug Flovent : 1760 mcg daily | Placebo : daily | ||
All Cause Mortality |
||||
| Flovent 1760 mcg | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/28 (0%) | 0/14 (0%) | ||
Serious Adverse Events |
||||
| Flovent 1760 mcg | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/28 (0%) | 0/14 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Flovent 1760 mcg | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 19/28 (67.9%) | 9/14 (64.3%) | ||
| Eye disorders | ||||
| General Disorders | 0/28 (0%) | 0 | 2/14 (14.3%) | 2 |
| Gastrointestinal disorders | ||||
| General Disorders | 7/28 (25%) | 10 | 2/14 (14.3%) | 2 |
| General disorders | ||||
| General Disorders | 1/28 (3.6%) | 1 | 1/14 (7.1%) | 1 |
| Immune system disorders | ||||
| General Disorders | 2/28 (7.1%) | 3 | 0/14 (0%) | 0 |
| Infections and infestations | ||||
| General Disorders | 3/28 (10.7%) | 4 | 3/14 (21.4%) | 3 |
| Injury, poisoning and procedural complications | ||||
| General Disorders | 1/28 (3.6%) | 1 | 0/14 (0%) | 0 |
| Investigations | ||||
| General Disorders | 5/28 (17.9%) | 5 | 1/14 (7.1%) | 4 |
| Nervous system disorders | ||||
| General Disorders | 4/28 (14.3%) | 5 | 0/14 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| General Disorders | 3/28 (10.7%) | 6 | 3/14 (21.4%) | 3 |
| Skin and subcutaneous tissue disorders | ||||
| General Disorders | 0/28 (0%) | 0 | 1/14 (7.1%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Marc E Rothenberg |
|---|---|
| Organization | Cincinnati Children's Hospital Medical Center |
| Phone | 513-636-7177 |
| rothenberg@cchmc.org |
- 06-10-07