Budesonide Versus Fluticasone for Treatment of Eosinophilic Esophagitis

• Sponsor: University of North Carolina, Chapel Hill (Other)
• Overall Status: Completed
• CT.gov ID: NCT02019758
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 129
• Location: 1
• Arms: 2
• Actual Duration (Months): 51
• Patients Per Site Per Month: 2.5

Study Details

Study Description

Brief Summary

Purpose: To determine whether oral viscous budesonide (OVB) or fluticasone metered dose inhaler (MDI) most effectively treats EoE by improving histologic findings and symptoms, which medication provides a more durable treatment response, and whether biomarkers can predict treatment response.

Participants: A total of up to 200 16-80 year old patients with a new diagnosis of eosinophilic esophagitis (EoE) who are referred for upper endoscopy will be consented with a target of 122 randomized.

Procedures: This will be a prospective, randomized, double-blind, double-dummy, clinical trial comparing OVB to fluticasone MDI for treatment of EoE. This overall study design will generate data for all three Aims

Condition or Disease	Intervention/Treatment	Phase
Eosinophilic Esophagitis	Drug: Oral Viscous Budesonide; Drug: Fluticasone MDI; Drug: Placebo slurry; Drug: Placebo inhaler	Phase 4

Detailed Description

This will be a prospective, randomized, double-blind, double-dummy, clinical trial comparing oral viscous budesonide (OVB) to fluticasone metered dose inhaler (MDI) for treatment of EoE. A total of 122 subjects aged 16-80 years old will be randomized in a 1:1 fashion to one of two active treatment arms: OVB + placebo inhaler or fluticasone MDI + placebo slurry.

In the first arm, subjects will be treated with OVB at a dose of 1 mg twice daily, and they will also be instructed to use a placebo inhaler identical to the fluticasone MDI, with instructions to swallow 4 puffs twice daily. The OVB is a slurry equivalent to what is used clinically: 1 mg/4 mL aqueous budesonide mixed with 10 g of sucralose. Rather than asking the subjects to mix the slurry on their own and risk inconsistent formulations, the University of North Carolina (UNC) investigational drug pharmacy (IDP) will provide pre-mixed OVB to all patients. The IDP will also provide placebo inhalers to all patients. The dose for OVB has been chosen because it is the most commonly studied dose, including one prior study led by this Principal Investigator, so we can accurately estimate response rates.

In the second arm, subjects will be treated with fluticasone MDI at a dose of 880 mcg twice daily (4 puffs of a 220 mcg inhaler twice daily), and they will also be instructed to take 4 mL twice daily of a placebo slurry of sucralose identical in consistency and taste to the OVB. The UNC investigational drug pharmacy (IDP) will provide the fluticasone MDIs and pre-mixed placebo slurries to all patients. The dose for fluticasone MDI has been chosen because this is the most commonly used dose in adolescents and adults with EoE, so effect estimates are also available.

For both arms, the slurry will be administered first, the MDI will be administered 15 minutes later, and patients will take nothing by mouth for an additional 30 minutes.

Subjects will receive 8 weeks of treatment and will then be monitored for up to 52 weeks for recurrence of symptoms.

Study Design

• Study Type: Interventional
• Actual Enrollment: 129 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Budesonide Versus Fluticasone for Treatment of Eosinophilic Esophagitis
• Actual Study Start Date: Jan 1, 2015
• Actual Primary Completion Date: May 1, 2018
• Actual Study Completion Date: Apr 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Oral Viscous Budesonide (OVB) Subjects will be treated with OVB at a dose of 1 mg twice daily, and they will also be instructed to use a placebo inhaler identical to the fluticasone MDI, with instructions to swallow 4 puffs twice daily.	Drug: Oral Viscous Budesonide; Oral Viscous Budesonide - 1 mg/4 mL, 4 mL of slurry twice daily; Other Names: Pulmicort ; Drug: Placebo inhaler; Placebo inhaler - 4 puffs twice daily; Other Names: Placebo
Active Comparator: Active Fluticasone MDI Subjects will be treated with fluticasone MDI at a dose of 880 mcg twice daily (4 puffs of a 220 mcg inhaler twice daily), and they will also be instructed to take 4 mL twice daily of a placebo slurry of sucralose identical in consistency and taste to the OVB.	Drug: Fluticasone MDI; Fluticasone multi-dose inhaler - 4 puffs twice daily (880 mcg, twice daily); Other Names: Flovent ; Drug: Placebo slurry; Slurry of sucralose - 4 mL twice daily; Other Names: Sucralose

Outcome Measures

Primary Outcome Measures

1. Post-Treatment Maximum Eosinophil Count (Aim 1) [8 weeks]

   To determine whether viscous budesonide is more effective than fluticasone MDI for improving post-treatment maximum esophageal eosinophil counts (measured in eosinophils per high powered field (eos/hpf)) in patients with eosinophilic esophagitis (EoE). The mean post-treatment maximum eosinophil count will be compared between the OVB and MDI groups using a two-sample t-test.

2. Post-treatment Dysphagia Score (Aim 1) [8 weeks]

   To determine whether viscous budesonide is more effective than fluticasone MDI for improving dysphagia (measured by the Daily Symptoms Questionnaire (DSQ)) in patients with EoE. The mean DSQ scores will be compared between the OVB and MDI groups using a two-sample t-test. The DSQ is a dysphagia severity score which ranges from 0-84, with higher numbers indicating more severe symptoms.

Secondary Outcome Measures

1. Post-treatment Endoscopic Severity (Aim 1) [8 weeks]

   Endoscopic severity will be quantified using the EoE Endoscopic Reference Score (EREFS) and compared between the two treatment arms. EREFS is a validated endoscopic severity score of key EoE endoscopic features (exudates, rings, edema, furrows, and strictures), and ranges from 0-9 with higher scores indicating higher endoscopic severity.

2. Percentage of Participants With Histologic Response of <15 Eos/Hpf [8 weeks]

   Percentage with histologic response, with response defined as <15 eos/hpf, will be compared between groups

3. Post-treatment Symptom Severity (Aim 1) [8 weeks]

   Post-treatment symptoms severity will be assessed with the EoE Symptom Activity Index (EEsAI), a validated dysphagia severity measure. The EEsAI ranges from 0-100, with higher scores indicating more severe symptoms; symptom remission is defined by a score <20.

4. Post-treatment Medication Compliance (Aim 1) [8 weeks]

   Medication compliance as measured by the percentage of medication appropriately used in each arm. For the slurry, this percentage is calculated after measuring the residual volume. For the inhaler, this percentage is calculated after measured using the residual weight.

5. Median Number of Days Until Symptom Recurrence (Aim 2) [Symptom recurrence or 1 year after completing the initial 8 week treatment]

   To test whether OVB results in less symptomatic recurrence than fluticasone MDI, the median number of days until symptom occurrence will be quantified between treatment end (week 8) and recurrent symptoms or study end (week 60) as the time of interest. Hazard ratio will be calculated using Cox proportional modeling.

6. Number of Subjects With Histologic Recurrence, Defined as ≥15 Eosinophils Per High-power Field, at Follow-up Endoscopy. [Symptom recurrence or 1 year after completing the initial 8 week treatment]

   To test whether OVB results in less histologic recurrence than fluticasone MDI, the number of subjects with ≥15 eosinophils per high-power field at follow-up endoscopy in each group will be compared using chi-square.

7. Mean Endoscopic Severity Score at Recurrence (Aim 2) [Symptom recurrence or 1 year after completing the initial 8 week treatment]

   Measurement of endoscopic severity, using the EoE Endoscopic Reference Score (EREFS) measure, at the time of recurrence. EREFS is a validated endoscopic severity score of key EoE endoscopic features (exudates, rings, edema, furrows, and strictures), and ranges from 0-9 with higher scores indicating higher endoscopic severity.

8. Mean Peak Eosinophil Count (Aim 2) [Symptom recurrence or 1 year after completing the initial 8 week treatment]

   This will assess the mean peak level of esophageal eosinophilia on biopsy (measured in peak eosinophil count - eos/hpf) at the time of recurrence

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria are as follows:

• Age: 16 - 80 years

• Subject is having a clinically indicated endoscopy for suspicious EoE and has been on twice daily (BID) proton pump inhibitor (PPI) for at least 8 weeks OR New diagnosis of EoE as per consensus guidelines. Cases must have symptoms of dysphagia, persistent esophageal eosinophilia (≥ 15 eosinophils in at least one high-power field) after 8 weeks of treatment with a twice daily proton-pump inhibitor, and other competing causes of esophageal eosinophilia excluded.

Exclusion criteria are as follows:

• Medical instability that precludes safely performing upper endoscopy

• Ongoing or recent symptoms of intestinal bleeding (throwing up blood, passing blood in the stool)

• Concomitant eosinophilic gastroenteritis

• Esophageal narrowing or stricturing that will not allow a standard 9 mm upper endoscopy scope to pass

• Cancer in the esophagus, stomach, or intestine

• Previous esophageal surgery

• Esophageal varices (dilated blood vessels in the esophagus)

• Current use of blood thinners like Plavix or Coumadin that are not stopped prior to endoscopy procedures

• Any corticosteroid exposure within the 4 weeks prior to their baseline endoscopic exam. Exclusionary corticosteroid exposure is defined as any swallowed topical steroids for EoE or systemic steroids for any condition within the four weeks prior to the baseline endoscopy. Corticosteroids used for asthma or intranasal corticosteroids are not an exclusion and are allowable.

• Pregnancy

• Inability to read or understand English

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of North Carolina, Chapel Hill	Chapel Hill	North Carolina	United States	27599

Sponsors and Collaborators

• University of North Carolina, Chapel Hill
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Evan S Dellon, MD, MPH, University of North Carolina, Chapel Hill

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 14, 2019

More Information

Publications

None provided.

• Responsible Party: University of North Carolina, Chapel Hill
• ClinicalTrials.gov Identifier: NCT02019758
• Other Study ID Numbers: 13-4047; R01DK101856
• First Posted: Dec 24, 2013
• Last Update Posted: Apr 27, 2020
• Last Verified: May 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Esophagitis; Eosinophilic Esophagitis; Fluticasone; Budesonide

Study Results

Participant Flow

Arm/Group Title	Oral Viscous Budesonide (OVB)	Active Fluticasone Metered Dose Inhaler (MDI)
Arm/Group Description	Subjects will be treated with Oral Viscous Budesonide (OVB) at a dose of 1 mg twice daily, and they will also be instructed to use a placebo inhaler identical to the fluticasone MDI, with instructions to swallow 4 puffs twice daily. Oral Viscous Budesonide: Oral Viscous Budesonide - 1mg/4 mL, 4 mL of slurry twice daily Placebo inhaler: Placebo inhaler - 4 puffs twice daily	Subjects will be treated with fluticasone Metered Dose Inhaler (MDI) at a dose of 880 mcg twice daily (4 puffs of a 220 mcg inhaler twice daily), and they will also be instructed to take 4 mL twice daily of a placebo slurry of sucralose identical in consistency and taste to the OVB. Fluticasone MDI: Fluticasone multi-dose inhaler - 4 puffs twice daily (880 mcg, twice daily) Placebo slurry: Slurry of sucralose - 4 mL twice daily
Period Title: Overall Study
STARTED	65	64
Received Intervention	64	63
Did Not Receive Intervention	1	1
Lost to Follow-up	8	8
COMPLETED	56	55
NOT COMPLETED	9	9

Baseline Characteristics

Arm/Group Title	Oral Viscous Budesonide (OVB)	Active Fluticasone MDI	Total
Arm/Group Description	Subjects will be treated with OVB at a dose of 1 mg twice daily, and they will also be instructed to use a placebo inhaler identical to the fluticasone MDI, with instructions to swallow 4 puffs twice daily. Oral Viscous Budesonide: Oral Viscous Budesonide - 1mg/4 mL, 4 mL of slurry twice daily Placebo inhaler: Placebo inhaler - 4 puffs twice daily	Subjects will be treated with fluticasone MDI at a dose of 880 mcg twice daily (4 puffs of a 220 mcg inhaler twice daily), and they will also be instructed to take 4 mL twice daily of a placebo slurry of sucralose identical in consistency and taste to the OVB. Fluticasone MDI: Fluticasone multi-dose inhaler - 4 puffs twice daily (880 mcg, twice daily) Placebo slurry: Slurry of sucralose - 4 mL twice daily	Total of all reporting groups
Overall Participants	65	64	129
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.2 (19.1)	39.0 (14.5)	38.6 (14.9)
Sex: Female, Male (Count of Participants)
Female	25 38.5%	20 31.3%	45 34.9%
Male	40 61.5%	44 68.8%	84 65.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 1.5%	1 1.6%	2 1.6%
White	63 96.9%	63 98.4%	126 97.7%
More than one race	1 1.5%	0 0%	1 0.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	65 100%	64 100%	129 100%

Outcome Measures

1. Primary Outcome

Title	Post-Treatment Maximum Eosinophil Count (Aim 1)
Description	To determine whether viscous budesonide is more effective than fluticasone MDI for improving post-treatment maximum esophageal eosinophil counts (measured in eosinophils per high powered field (eos/hpf)) in patients with eosinophilic esophagitis (EoE). The mean post-treatment maximum eosinophil count will be compared between the OVB and MDI groups using a two-sample t-test.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Viscous Budesonide (OVB)	Active Fluticasone MDI
Arm/Group Description	Subjects will be treated with OVB at a dose of 1 mg twice daily, and they will also be instructed to use a placebo inhaler identical to the fluticasone MDI, with instructions to swallow 4 puffs twice daily. Oral Viscous Budesonide: Oral Viscous Budesonide - 1mg/4 mL, 4 mL of slurry twice daily Placebo inhaler: Placebo inhaler - 4 puffs twice daily	Subjects will be treated with fluticasone MDI at a dose of 880 mcg twice daily (4 puffs of a 220 mcg inhaler twice daily), and they will also be instructed to take 4 mL twice daily of a placebo slurry of sucralose identical in consistency and taste to the OVB. Fluticasone MDI: Fluticasone multi-dose inhaler - 4 puffs twice daily (880 mcg, twice daily) Placebo slurry: Slurry of sucralose - 4 mL twice daily
Measure Participants	56	55
Mean (Standard Deviation) [eosinophils per high-power field]	14.7 (29.0)	20.9 (34.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral Viscous Budesonide (OVB), Active Fluticasone MDI
	Comments	The mean post-treatment maximum eosinophil count will be compared between the OVB and MDI groups using a two-sample t-test.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.31
	Comments
	Method	t-test, 2 sided
	Comments

2. Primary Outcome

Title	Post-treatment Dysphagia Score (Aim 1)
Description	To determine whether viscous budesonide is more effective than fluticasone MDI for improving dysphagia (measured by the Daily Symptoms Questionnaire (DSQ)) in patients with EoE. The mean DSQ scores will be compared between the OVB and MDI groups using a two-sample t-test. The DSQ is a dysphagia severity score which ranges from 0-84, with higher numbers indicating more severe symptoms.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Viscous Budesonide (OVB)	Active Fluticasone MDI
Arm/Group Description	Subjects will be treated with OVB at a dose of 1 mg twice daily, and they will also be instructed to use a placebo inhaler identical to the fluticasone MDI, with instructions to swallow 4 puffs twice daily. Oral Viscous Budesonide: Oral Viscous Budesonide - 1mg/4 mL, 4 mL of slurry twice daily Placebo inhaler: Placebo inhaler - 4 puffs twice daily	Subjects will be treated with fluticasone MDI at a dose of 880 mcg twice daily (4 puffs of a 220 mcg inhaler twice daily), and they will also be instructed to take 4 mL twice daily of a placebo slurry of sucralose identical in consistency and taste to the OVB. Fluticasone MDI: Fluticasone multi-dose inhaler - 4 puffs twice daily (880 mcg, twice daily) Placebo slurry: Slurry of sucralose - 4 mL twice daily
Measure Participants	56	55
Mean (Standard Deviation) [score on a scale]	4.8 (7.3)	4.2 (7.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral Viscous Budesonide (OVB), Active Fluticasone MDI
	Comments	The mean DSQ scores will be compared between the OVB and MDI groups using a two-sample t-test.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.70
	Comments
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Post-treatment Endoscopic Severity (Aim 1)
Description	Endoscopic severity will be quantified using the EoE Endoscopic Reference Score (EREFS) and compared between the two treatment arms. EREFS is a validated endoscopic severity score of key EoE endoscopic features (exudates, rings, edema, furrows, and strictures), and ranges from 0-9 with higher scores indicating higher endoscopic severity.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Viscous Budesonide (OVB)	Active Fluticasone MDI
Arm/Group Description	Subjects will be treated with OVB at a dose of 1 mg twice daily, and they will also be instructed to use a placebo inhaler identical to the fluticasone MDI, with instructions to swallow 4 puffs twice daily. Oral Viscous Budesonide: Oral Viscous Budesonide - 1mg/4 mL, 4 mL of slurry twice daily Placebo inhaler: Placebo inhaler - 4 puffs twice daily	Subjects will be treated with fluticasone MDI at a dose of 880 mcg twice daily (4 puffs of a 220 mcg inhaler twice daily), and they will also be instructed to take 4 mL twice daily of a placebo slurry of sucralose identical in consistency and taste to the OVB. Fluticasone MDI: Fluticasone multi-dose inhaler - 4 puffs twice daily (880 mcg, twice daily) Placebo slurry: Slurry of sucralose - 4 mL twice daily
Measure Participants	56	55
Mean (Standard Deviation) [score on a scale]	2.1 (1.7)	2.8 (2.2)

4. Secondary Outcome

Title	Percentage of Participants With Histologic Response of <15 Eos/Hpf
Description	Percentage with histologic response, with response defined as <15 eos/hpf, will be compared between groups
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Viscous Budesonide (OVB)	Active Fluticasone MDI
Arm/Group Description	Subjects will be treated with OVB at a dose of 1 mg twice daily, and they will also be instructed to use a placebo inhaler identical to the fluticasone MDI, with instructions to swallow 4 puffs twice daily. Oral Viscous Budesonide: Oral Viscous Budesonide - 1mg/4 mL, 4 mL of slurry twice daily Placebo inhaler: Placebo inhaler - 4 puffs twice daily	Subjects will be treated with fluticasone MDI at a dose of 880 mcg twice daily (4 puffs of a 220 mcg inhaler twice daily), and they will also be instructed to take 4 mL twice daily of a placebo slurry of sucralose identical in consistency and taste to the OVB. Fluticasone MDI: Fluticasone multi-dose inhaler - 4 puffs twice daily (880 mcg, twice daily) Placebo slurry: Slurry of sucralose - 4 mL twice daily
Measure Participants	56	55
Number [Percent responders]	71	64

5. Secondary Outcome

Title	Post-treatment Symptom Severity (Aim 1)
Description	Post-treatment symptoms severity will be assessed with the EoE Symptom Activity Index (EEsAI), a validated dysphagia severity measure. The EEsAI ranges from 0-100, with higher scores indicating more severe symptoms; symptom remission is defined by a score <20.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Viscous Budesonide (OVB)	Active Fluticasone MDI
Arm/Group Description	Subjects will be treated with OVB at a dose of 1 mg twice daily, and they will also be instructed to use a placebo inhaler identical to the fluticasone MDI, with instructions to swallow 4 puffs twice daily. Oral Viscous Budesonide: Oral Viscous Budesonide - 1mg/4 mL, 4 mL of slurry twice daily Placebo inhaler: Placebo inhaler - 4 puffs twice daily	Subjects will be treated with fluticasone MDI at a dose of 880 mcg twice daily (4 puffs of a 220 mcg inhaler twice daily), and they will also be instructed to take 4 mL twice daily of a placebo slurry of sucralose identical in consistency and taste to the OVB. Fluticasone MDI: Fluticasone multi-dose inhaler - 4 puffs twice daily (880 mcg, twice daily) Placebo slurry: Slurry of sucralose - 4 mL twice daily
Measure Participants	56	55
Mean (Standard Deviation) [score on a scale]	22.1 (18.9)	28.0 (20.4)

6. Secondary Outcome

Title	Post-treatment Medication Compliance (Aim 1)
Description	Medication compliance as measured by the percentage of medication appropriately used in each arm. For the slurry, this percentage is calculated after measuring the residual volume. For the inhaler, this percentage is calculated after measured using the residual weight.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Viscous Budesonide (OVB)	Active Fluticasone MDI
Arm/Group Description	Subjects will be treated with OVB at a dose of 1 mg twice daily, and they will also be instructed to use a placebo inhaler identical to the fluticasone MDI, with instructions to swallow 4 puffs twice daily. Oral Viscous Budesonide: Oral Viscous Budesonide - 1mg/4 mL, 4 mL of slurry twice daily Placebo inhaler: Placebo inhaler - 4 puffs twice daily	Subjects will be treated with fluticasone MDI at a dose of 880 mcg twice daily (4 puffs of a 220 mcg inhaler twice daily), and they will also be instructed to take 4 mL twice daily of a placebo slurry of sucralose identical in consistency and taste to the OVB. Fluticasone MDI: Fluticasone multi-dose inhaler - 4 puffs twice daily (880 mcg, twice daily) Placebo slurry: Slurry of sucralose - 4 mL twice daily
Measure Participants	56	55
Number [Percentage of medication used]	87	85

7. Secondary Outcome

Title	Median Number of Days Until Symptom Recurrence (Aim 2)
Description	To test whether OVB results in less symptomatic recurrence than fluticasone MDI, the median number of days until symptom occurrence will be quantified between treatment end (week 8) and recurrent symptoms or study end (week 60) as the time of interest. Hazard ratio will be calculated using Cox proportional modeling.
Time Frame	Symptom recurrence or 1 year after completing the initial 8 week treatment

Outcome Measure Data

Analysis Population Description

This population reflects only those patients who achieved histologic remission (<15 eosinophils per high-power field) after the blinded phase, entered the observation phase, and had symptom outcome data.

Arm/Group Title	Oral Viscous Budesonide (OVB)	Active Fluticasone MDI
Arm/Group Description	Subjects will be treated with OVB at a dose of 1 mg twice daily, and they will also be instructed to use a placebo inhaler identical to the fluticasone MDI, with instructions to swallow 4 puffs twice daily. Oral Viscous Budesonide: Oral Viscous Budesonide - 1mg/4 mL, 4 mL of slurry twice daily Placebo inhaler: Placebo inhaler - 4 puffs twice daily	Subjects will be treated with fluticasone MDI at a dose of 880 mcg twice daily (4 puffs of a 220 mcg inhaler twice daily), and they will also be instructed to take 4 mL twice daily of a placebo slurry of sucralose identical in consistency and taste to the OVB. Fluticasone MDI: Fluticasone multi-dose inhaler - 4 puffs twice daily (880 mcg, twice daily) Placebo slurry: Slurry of sucralose - 4 mL twice daily
Measure Participants	33	25
Median (Standard Error) [Days]	263 (42.0)	224 (66.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral Viscous Budesonide (OVB), Active Fluticasone MDI
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.52 to 2.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Number of Subjects With Histologic Recurrence, Defined as ≥15 Eosinophils Per High-power Field, at Follow-up Endoscopy.
Description	To test whether OVB results in less histologic recurrence than fluticasone MDI, the number of subjects with ≥15 eosinophils per high-power field at follow-up endoscopy in each group will be compared using chi-square.
Time Frame	Symptom recurrence or 1 year after completing the initial 8 week treatment

Outcome Measure Data

Analysis Population Description

This population reflects only those patients who achieved histologic remission (<15 eosinophils per high-power field) after the blinded phase, entered the observation phase, and had endoscopic and histologic data available.

Arm/Group Title	Oral Viscous Budesonide (OVB)	Active Fluticasone MDI
Arm/Group Description	Subjects will be treated with OVB at a dose of 1 mg twice daily, and they will also be instructed to use a placebo inhaler identical to the fluticasone MDI, with instructions to swallow 4 puffs twice daily. Oral Viscous Budesonide: Oral Viscous Budesonide - 1mg/4 mL, 4 mL of slurry twice daily Placebo inhaler: Placebo inhaler - 4 puffs twice daily	Subjects will be treated with fluticasone MDI at a dose of 880 mcg twice daily (4 puffs of a 220 mcg inhaler twice daily), and they will also be instructed to take 4 mL twice daily of a placebo slurry of sucralose identical in consistency and taste to the OVB. Fluticasone MDI: Fluticasone multi-dose inhaler - 4 puffs twice daily (880 mcg, twice daily) Placebo slurry: Slurry of sucralose - 4 mL twice daily
Measure Participants	25	25
Count of Participants [Participants]	22 33.8%	17 26.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral Viscous Budesonide (OVB), Active Fluticasone MDI
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Chi-squared
	Comments

9. Secondary Outcome

Title	Mean Endoscopic Severity Score at Recurrence (Aim 2)
Description	Measurement of endoscopic severity, using the EoE Endoscopic Reference Score (EREFS) measure, at the time of recurrence. EREFS is a validated endoscopic severity score of key EoE endoscopic features (exudates, rings, edema, furrows, and strictures), and ranges from 0-9 with higher scores indicating higher endoscopic severity.
Time Frame	Symptom recurrence or 1 year after completing the initial 8 week treatment

Outcome Measure Data

Analysis Population Description

This population reflects only those patients who achieved histologic remission (<15 eosinophils per high-power field) after the blinded phase, entered the observation phase, and had endoscopic and histologic outcome data.

Arm/Group Title	Oral Viscous Budesonide (OVB)	Active Fluticasone MDI
Arm/Group Description	Subjects will be treated with OVB at a dose of 1 mg twice daily, and they will also be instructed to use a placebo inhaler identical to the fluticasone MDI, with instructions to swallow 4 puffs twice daily. Oral Viscous Budesonide: Oral Viscous Budesonide - 1mg/4 mL, 4 mL of slurry twice daily Placebo inhaler: Placebo inhaler - 4 puffs twice daily	Subjects will be treated with fluticasone MDI at a dose of 880 mcg twice daily (4 puffs of a 220 mcg inhaler twice daily), and they will also be instructed to take 4 mL twice daily of a placebo slurry of sucralose identical in consistency and taste to the OVB. Fluticasone MDI: Fluticasone multi-dose inhaler - 4 puffs twice daily (880 mcg, twice daily) Placebo slurry: Slurry of sucralose - 4 mL twice daily
Measure Participants	25	25
Mean (Standard Deviation) [score on a scale]	4.8 (1.7)	4.3 (2.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral Viscous Budesonide (OVB), Active Fluticasone MDI
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	t-test, 2 sided
	Comments

10. Secondary Outcome

Title	Mean Peak Eosinophil Count (Aim 2)
Description	This will assess the mean peak level of esophageal eosinophilia on biopsy (measured in peak eosinophil count - eos/hpf) at the time of recurrence
Time Frame	Symptom recurrence or 1 year after completing the initial 8 week treatment

Outcome Measure Data

Analysis Population Description

This population reflects only those patients who achieved histologic remission (<15 eosinophils per high-power field) after the blinded phase, entered the observation phase, and had endoscopic and histologic outcome data.

Arm/Group Title	Oral Viscous Budesonide (OVB)	Active Fluticasone MDI
Arm/Group Description	Subjects will be treated with OVB at a dose of 1 mg twice daily, and they will also be instructed to use a placebo inhaler identical to the fluticasone MDI, with instructions to swallow 4 puffs twice daily. Oral Viscous Budesonide: Oral Viscous Budesonide - 1mg/4 mL, 4 mL of slurry twice daily Placebo inhaler: Placebo inhaler - 4 puffs twice daily	Subjects will be treated with fluticasone MDI at a dose of 880 mcg twice daily (4 puffs of a 220 mcg inhaler twice daily), and they will also be instructed to take 4 mL twice daily of a placebo slurry of sucralose identical in consistency and taste to the OVB. Fluticasone MDI: Fluticasone multi-dose inhaler - 4 puffs twice daily (880 mcg, twice daily) Placebo slurry: Slurry of sucralose - 4 mL twice daily
Measure Participants	25	25
Mean (Standard Deviation) [eosinophils per high-power field]	71.8 (52.9)	35.0 (29.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral Viscous Budesonide (OVB), Active Fluticasone MDI
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	8 weeks over the initial treatment period.
Arm/Group Title	Oral Viscous Budesonide (OVB)		Active Fluticasone MDI
Arm/Group Description	Subjects will be treated with OVB at a dose of 1 mg twice daily, and they will also be instructed to use a placebo inhaler identical to the fluticasone MDI, with instructions to swallow 4 puffs twice daily. Oral Viscous Budesonide: Oral Viscous Budesonide - 1mg/4 mL, 4 mL of slurry twice daily Placebo inhaler: Placebo inhaler - 4 puffs twice daily		Subjects will be treated with fluticasone MDI at a dose of 880 mcg twice daily (4 puffs of a 220 mcg inhaler twice daily), and they will also be instructed to take 4 mL twice daily of a placebo slurry of sucralose identical in consistency and taste to the OVB. Fluticasone MDI: Fluticasone multi-dose inhaler - 4 puffs twice daily (880 mcg, twice daily) Placebo slurry: Slurry of sucralose - 4 mL twice daily
All Cause Mortality
	Oral Viscous Budesonide (OVB)		Active Fluticasone MDI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/65 (0%)		0/64 (0%)
Serious Adverse Events
	Oral Viscous Budesonide (OVB)		Active Fluticasone MDI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/65 (0%)		1/64 (1.6%)
Gastrointestinal disorders
Food impaction	0/65 (0%)		1/64 (1.6%)
Other (Not Including Serious) Adverse Events
	Oral Viscous Budesonide (OVB)		Active Fluticasone MDI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/65 (15.4%)		15/64 (23.4%)
Cardiac disorders
chest pain	0/65 (0%)		1/64 (1.6%)
Gastrointestinal disorders
esophageal candidiasis	8/65 (12.3%)		10/64 (15.6%)
oral candidiasis	2/65 (3.1%)		1/64 (1.6%)
sore throat	0/65 (0%)		2/64 (3.1%)
Infections and infestations
pneumonia	0/65 (0%)		1/64 (1.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.