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Budesonide Versus Fluticasone for Treatment of Eosinophilic Esophagitis

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ClinicalTrials.gov Identifier: NCT02019758
Recruitment Status : Completed
First Posted : December 24, 2013
Results First Posted : April 26, 2019
Last Update Posted : May 15, 2019
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Eosinophilic Esophagitis
Interventions Drug: Oral Viscous Budesonide
Drug: Fluticasone MDI
Drug: Placebo slurry
Drug: Placebo inhaler
Enrollment 129
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Oral Viscous Budesonide (OVB) Active Fluticasone Metered Dose Inhaler (MDI)
Hide 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 [1] 64 [2]
Received Intervention 64 63
Did Not Receive Intervention 1 1
Lost to Follow-up 8 [3] 8 [3]
Completed 56 55 [3]
Not Completed 9 9
[1]
64 received intervention; 1 did not receive intervention
[2]
63 received intervention; 1 did not receive intervention
[3]
8 were lost to follow-up and did not undergo week 8 endoscopy or other outcome assessments
Arm/Group Title Oral Viscous Budesonide (OVB) Active Fluticasone MDI Total
Hide 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 Number of Baseline Participants 65 64 129
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 65 participants 64 participants 129 participants
36.2  (19.1) 39.0  (14.5) 38.6  (14.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 64 participants 129 participants
Female
25
  38.5%
20
  31.3%
45
  34.9%
Male
40
  61.5%
44
  68.8%
84
  65.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 64 participants 129 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
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
   0.0%
1
   0.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 65 participants 64 participants 129 participants
65
 100.0%
64
 100.0%
129
 100.0%
1.Primary Outcome
Title Post-treatment Maximum Eosinophil Count (Aim 1)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oral Viscous Budesonide (OVB) Active Fluticasone MDI
Hide 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

Overall Number of Participants Analyzed 56 55
Mean (Standard Deviation)
Unit of Measure: eosinophils per high-power field
14.7  (29.0) 20.9  (34.3)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.31
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
2.Primary Outcome
Title Post-treatment Dysphagia Score (Aim 1)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oral Viscous Budesonide (OVB) Active Fluticasone MDI
Hide 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

Overall Number of Participants Analyzed 56 55
Mean (Standard Deviation)
Unit of Measure: score on a scale
4.8  (7.3) 4.2  (7.5)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.70
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
3.Secondary Outcome
Title Post-treatment Endoscopic Severity (Aim 1)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oral Viscous Budesonide (OVB) Active Fluticasone MDI
Hide 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

Overall Number of Participants Analyzed 56 55
Mean (Standard Deviation)
Unit of Measure: 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
Hide Description Percentage with histologic response, with response defined as <15 eos/hpf, will be compared between groups
Time Frame 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oral Viscous Budesonide (OVB) Active Fluticasone MDI
Hide 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

Overall Number of Participants Analyzed 56 55
Measure Type: Number
Unit of Measure: Percent responders
71 64
5.Secondary Outcome
Title Post-treatment Symptom Severity (Aim 1)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oral Viscous Budesonide (OVB) Active Fluticasone MDI
Hide 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

Overall Number of Participants Analyzed 56 55
Mean (Standard Deviation)
Unit of Measure: score on a scale
22.1  (18.9) 28.0  (20.4)
6.Secondary Outcome
Title Post-treatment Medication Compliance (Aim 1)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Oral Viscous Budesonide (OVB) Active Fluticasone MDI
Hide 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

Overall Number of Participants Analyzed 56 55
Measure Type: Number
Unit of Measure: Percentage of medication used
87 85
7.Secondary Outcome
Title Symptom Recurrence (Aim 2)
Hide Description To test whether OVB results in less symptomatic recurrence than fluticasone MDI, survival analysis will be performed with the interval between treatment end (week 8) and recurrent symptoms or study end (week 60) as the time of interest. A Kaplan-Meier curve will be constructed comparing the time until symptom recurrence in both study groups using the log-rank test.
Time Frame Symptom recurrence or 1 year after completing the initial 8 week treatment
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Histologic Recurrence (Aim 2)
Hide Description To test whether OVB results in less histologic recurrence than fluticasone MDI, the proportion of subjects with ≥15 eos/hpf 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 Not Reported
9.Secondary Outcome
Title Endoscopic Severity at Recurrence (Aim 2)
Hide Description Measurement of endoscopic severity, using the validated EREFS measure, at the time of recurrence
Time Frame Symptom recurrence or 1 year after completing the initial 8 week treatment
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Peak Eosinophil Count (Aim 2)
Hide Description This will assess the 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 Not Reported
11.Other Pre-specified Outcome
Title Baseline Immunohistochemical (IHC) Staining and Histologic Response (Aim 3)
Hide Description

To determine whether baseline immunohistochemical (IHC) staining of esophageal biopsies for major basic protein (MBP), eotaxin-3, and mast cell tryptase (MCT) is associated with histologic response in EoE patients treated with topical corticosteroid therapy. The mean baseline cellular staining for each biomarker (MBP, eotaxin-3, and MCT) will be compared between the responder and non-responder groups using a two-sample t-test.

Note: Results are not yet available for this outcome, as these samples will be batch processed together with other histologic data being collected for this trial which may be collected up until 1 year after completing the initial 8-week treatment and are still being collected.

Time Frame Enrollment (Day 1)
Outcome Measure Data Not Reported
Time Frame 8 weeks over the initial treatment period.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Oral Viscous Budesonide (OVB) Active Fluticasone MDI
Hide 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 (%) Affected / at Risk (%)
Total   0/65 (0.00%)   0/64 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Oral Viscous Budesonide (OVB) Active Fluticasone MDI
Affected / at Risk (%) Affected / at Risk (%)
Total   0/65 (0.00%)   1/64 (1.56%) 
Gastrointestinal disorders     
Food impaction *  0/65 (0.00%)  1/64 (1.56%) 
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Oral Viscous Budesonide (OVB) Active Fluticasone MDI
Affected / at Risk (%) Affected / at Risk (%)
Total   10/65 (15.38%)   15/64 (23.44%) 
Cardiac disorders     
chest pain *  0/65 (0.00%)  1/64 (1.56%) 
Gastrointestinal disorders     
esophageal candidiasis *  8/65 (12.31%)  10/64 (15.63%) 
oral candidiasis *  2/65 (3.08%)  1/64 (1.56%) 
sore throat *  0/65 (0.00%)  2/64 (3.13%) 
Infections and infestations     
pneumonia *  0/65 (0.00%)  1/64 (1.56%) 
*
Indicates events were collected by non-systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Evan S. Dellon, MD MPH
Organization: University of North Carolina at Chapel Hill
Phone: 919-966-2513
Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT02019758     History of Changes
Other Study ID Numbers: 13-4047
R01DK101856 ( U.S. NIH Grant/Contract )
First Submitted: December 18, 2013
First Posted: December 24, 2013
Results First Submitted: April 3, 2019
Results First Posted: April 26, 2019
Last Update Posted: May 15, 2019