Trial Outcomes & Findings for Budesonide Versus Fluticasone for Treatment of Eosinophilic Esophagitis (NCT NCT02019758)
NCT ID: NCT02019758
Last Updated: 2020-04-27
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
129 participants
Primary outcome timeframe
8 weeks
Results posted on
2020-04-27
Participant Flow
Participant milestones
| Measure |
Oral Viscous Budesonide (OVB)
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
|
Active Fluticasone Metered Dose Inhaler (MDI)
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
|
|---|---|---|
|
Overall Study
STARTED
|
65
|
64
|
|
Overall Study
Received Intervention
|
64
|
63
|
|
Overall Study
Did Not Receive Intervention
|
1
|
1
|
|
Overall Study
Lost to Follow-up
|
8
|
8
|
|
Overall Study
COMPLETED
|
56
|
55
|
|
Overall Study
NOT COMPLETED
|
9
|
9
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Budesonide Versus Fluticasone for Treatment of Eosinophilic Esophagitis
Baseline characteristics by cohort
| Measure |
Oral Viscous Budesonide (OVB)
n=65 Participants
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
|
Active Fluticasone MDI
n=64 Participants
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
n=129 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
36.2 years
STANDARD_DEVIATION 19.1 • n=5 Participants
|
39.0 years
STANDARD_DEVIATION 14.5 • n=7 Participants
|
38.6 years
STANDARD_DEVIATION 14.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
25 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
45 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
40 Participants
n=5 Participants
|
44 Participants
n=7 Participants
|
84 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
63 Participants
n=5 Participants
|
63 Participants
n=7 Participants
|
126 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
65 Participants
n=5 Participants
|
64 Participants
n=7 Participants
|
129 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 8 weeksTo 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.
Outcome measures
| Measure |
Oral Viscous Budesonide (OVB)
n=56 Participants
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
|
Active Fluticasone MDI
n=55 Participants
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
|
|---|---|---|
|
Post-Treatment Maximum Eosinophil Count (Aim 1)
|
14.7 eosinophils per high-power field
Standard Deviation 29.0
|
20.9 eosinophils per high-power field
Standard Deviation 34.3
|
PRIMARY outcome
Timeframe: 8 weeksTo 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.
Outcome measures
| Measure |
Oral Viscous Budesonide (OVB)
n=56 Participants
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
|
Active Fluticasone MDI
n=55 Participants
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
|
|---|---|---|
|
Post-treatment Dysphagia Score (Aim 1)
|
4.8 score on a scale
Standard Deviation 7.3
|
4.2 score on a scale
Standard Deviation 7.5
|
SECONDARY outcome
Timeframe: 8 weeksEndoscopic 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.
Outcome measures
| Measure |
Oral Viscous Budesonide (OVB)
n=56 Participants
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
|
Active Fluticasone MDI
n=55 Participants
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
|
|---|---|---|
|
Post-treatment Endoscopic Severity (Aim 1)
|
2.1 score on a scale
Standard Deviation 1.7
|
2.8 score on a scale
Standard Deviation 2.2
|
SECONDARY outcome
Timeframe: 8 weeksPercentage with histologic response, with response defined as \<15 eos/hpf, will be compared between groups
Outcome measures
| Measure |
Oral Viscous Budesonide (OVB)
n=56 Participants
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
|
Active Fluticasone MDI
n=55 Participants
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
|
|---|---|---|
|
Percentage of Participants With Histologic Response of <15 Eos/Hpf
|
71 Percent responders
|
64 Percent responders
|
SECONDARY outcome
Timeframe: 8 weeksPost-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.
Outcome measures
| Measure |
Oral Viscous Budesonide (OVB)
n=56 Participants
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
|
Active Fluticasone MDI
n=55 Participants
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
|
|---|---|---|
|
Post-treatment Symptom Severity (Aim 1)
|
22.1 score on a scale
Standard Deviation 18.9
|
28.0 score on a scale
Standard Deviation 20.4
|
SECONDARY outcome
Timeframe: 8 weeksMedication 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.
Outcome measures
| Measure |
Oral Viscous Budesonide (OVB)
n=56 Participants
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
|
Active Fluticasone MDI
n=55 Participants
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
|
|---|---|---|
|
Post-treatment Medication Compliance (Aim 1)
|
87 Percentage of medication used
|
85 Percentage of medication used
|
SECONDARY outcome
Timeframe: Symptom recurrence or 1 year after completing the initial 8 week treatmentPopulation: 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.
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.
Outcome measures
| Measure |
Oral Viscous Budesonide (OVB)
n=33 Participants
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
|
Active Fluticasone MDI
n=25 Participants
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
|
|---|---|---|
|
Median Number of Days Until Symptom Recurrence (Aim 2)
|
263 Days
Standard Error 42.0
|
224 Days
Standard Error 66.3
|
SECONDARY outcome
Timeframe: Symptom recurrence or 1 year after completing the initial 8 week treatmentPopulation: 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.
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.
Outcome measures
| Measure |
Oral Viscous Budesonide (OVB)
n=25 Participants
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
|
Active Fluticasone MDI
n=25 Participants
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
|
|---|---|---|
|
Number of Subjects With Histologic Recurrence, Defined as ≥15 Eosinophils Per High-power Field, at Follow-up Endoscopy.
|
22 Participants
|
17 Participants
|
SECONDARY outcome
Timeframe: Symptom recurrence or 1 year after completing the initial 8 week treatmentPopulation: 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.
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.
Outcome measures
| Measure |
Oral Viscous Budesonide (OVB)
n=25 Participants
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
|
Active Fluticasone MDI
n=25 Participants
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
|
|---|---|---|
|
Mean Endoscopic Severity Score at Recurrence (Aim 2)
|
4.8 score on a scale
Standard Deviation 1.7
|
4.3 score on a scale
Standard Deviation 2.0
|
SECONDARY outcome
Timeframe: Symptom recurrence or 1 year after completing the initial 8 week treatmentPopulation: 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.
This will assess the mean peak level of esophageal eosinophilia on biopsy (measured in peak eosinophil count - eos/hpf) at the time of recurrence
Outcome measures
| Measure |
Oral Viscous Budesonide (OVB)
n=25 Participants
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
|
Active Fluticasone MDI
n=25 Participants
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
|
|---|---|---|
|
Mean Peak Eosinophil Count (Aim 2)
|
71.8 eosinophils per high-power field
Standard Deviation 52.9
|
35.0 eosinophils per high-power field
Standard Deviation 29.4
|
Adverse Events
Oral Viscous Budesonide (OVB)
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Active Fluticasone MDI
Serious events: 1 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Oral Viscous Budesonide (OVB)
n=65 participants at risk
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
|
Active Fluticasone MDI
n=64 participants at risk
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
|
|---|---|---|
|
Gastrointestinal disorders
Food impaction
|
0.00%
0/65 • 8 weeks over the initial treatment period.
|
1.6%
1/64 • 8 weeks over the initial treatment period.
|
Other adverse events
| Measure |
Oral Viscous Budesonide (OVB)
n=65 participants at risk
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
|
Active Fluticasone MDI
n=64 participants at risk
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
|
|---|---|---|
|
Gastrointestinal disorders
esophageal candidiasis
|
12.3%
8/65 • 8 weeks over the initial treatment period.
|
15.6%
10/64 • 8 weeks over the initial treatment period.
|
|
Gastrointestinal disorders
oral candidiasis
|
3.1%
2/65 • 8 weeks over the initial treatment period.
|
1.6%
1/64 • 8 weeks over the initial treatment period.
|
|
Gastrointestinal disorders
sore throat
|
0.00%
0/65 • 8 weeks over the initial treatment period.
|
3.1%
2/64 • 8 weeks over the initial treatment period.
|
|
Cardiac disorders
chest pain
|
0.00%
0/65 • 8 weeks over the initial treatment period.
|
1.6%
1/64 • 8 weeks over the initial treatment period.
|
|
Infections and infestations
pneumonia
|
0.00%
0/65 • 8 weeks over the initial treatment period.
|
1.6%
1/64 • 8 weeks over the initial treatment period.
|
Additional Information
Evan S. Dellon, MD MPH
University of North Carolina at Chapel Hill
Phone: 919-966-2513
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place