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| ID | Type | Description | Link |
|---|---|---|---|
| R01DK101856 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Oral Viscous Budesonide (OVB) | Active Comparator | 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. |
|
| Active Fluticasone MDI | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oral Viscous Budesonide | Drug | Oral Viscous Budesonide - 1 mg/4 mL, 4 mL of slurry twice daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Post-Treatment Maximum Eosinophil Count (Aim 1) | 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. | 8 weeks |
| Post-treatment Dysphagia Score (Aim 1) | 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. | 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Post-treatment Endoscopic Severity (Aim 1) | 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. | 8 weeks |
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Inclusion criteria are as follows:
Exclusion criteria are as follows:
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| Name | Affiliation | Role |
|---|---|---|
| Evan S Dellon, MD, MPH | University of North Carolina, Chapel Hill | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of North Carolina, Chapel Hill | Chapel Hill | North Carolina | 27599 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33009060 | Derived | Safroneeva E, Cotton CC, Schoepfer AM, Zwahlen M, Woosley JT, Dellon ES. Dilation Modifies Association Between Symptoms and Esophageal Eosinophilia in Adult Patients With Eosinophilic Esophagitis. Am J Gastroenterol. 2020 Dec;115(12):2098-2102. doi: 10.14309/ajg.0000000000000957. | |
| 31499249 | Derived | Dellon ES, Woosley JT, Arrington A, McGee SJ, Covington J, Moist SE, Gebhart JH, Galanko JA, Baron JA, Shaheen NJ. Rapid Recurrence of Eosinophilic Esophagitis Activity After Successful Treatment in the Observation Phase of a Randomized, Double-Blind, Double-Dummy Trial. Clin Gastroenterol Hepatol. 2020 Jun;18(7):1483-1492.e2. doi: 10.1016/j.cgh.2019.08.050. Epub 2019 Sep 6. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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 |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. Oral Viscous Budesonide: Oral Viscous Budesonide - 1mg/4 mL, 4 mL of slurry twice daily Placebo inhaler: Placebo inhaler - 4 puffs twice daily |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Post-Treatment Maximum Eosinophil Count (Aim 1) | 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. | Posted | Mean | Standard Deviation | eosinophils per high-power field | 8 weeks |
|
8 weeks over the initial treatment period.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. Oral Viscous Budesonide: Oral Viscous Budesonide - 1mg/4 mL, 4 mL of slurry twice daily Placebo inhaler: Placebo inhaler - 4 puffs twice daily |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Food impaction | Gastrointestinal disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| esophageal candidiasis | Gastrointestinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Evan S. Dellon, MD MPH | University of North Carolina at Chapel Hill | 919-966-2513 | edellon@med.unc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 14, 2019 | Apr 3, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D057765 | Eosinophilic Esophagitis |
| ID | Term |
|---|---|
| D004941 | Esophagitis |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D019819 | Budesonide |
| D000068298 | Fluticasone |
| C026285 | trichlorosucrose |
| ID | Term |
|---|---|
| D011282 | Pregnenediones |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 |
Not provided
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Not provided
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| Fluticasone MDI | Drug | Fluticasone multi-dose inhaler - 4 puffs twice daily (880 mcg, twice daily) |
|
|
| Placebo slurry | Drug | Slurry of sucralose - 4 mL twice daily |
|
|
| Placebo inhaler | Drug | Placebo inhaler - 4 puffs twice daily |
|
|
| Percentage of Participants With Histologic Response of <15 Eos/Hpf | Percentage with histologic response, with response defined as <15 eos/hpf, will be compared between groups | 8 weeks |
| Post-treatment Symptom Severity (Aim 1) | 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. | 8 weeks |
| Post-treatment Medication Compliance (Aim 1) | 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. | 8 weeks |
| Median Number of Days Until Symptom Recurrence (Aim 2) | 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. | Symptom recurrence or 1 year after completing the initial 8 week treatment |
| Number of Subjects With Histologic Recurrence, Defined as ≥15 Eosinophils Per High-power Field, at Follow-up Endoscopy. | 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. | Symptom recurrence or 1 year after completing the initial 8 week treatment |
| Mean Endoscopic Severity Score at Recurrence (Aim 2) | 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. | Symptom recurrence or 1 year after completing the initial 8 week treatment |
| Mean Peak Eosinophil Count (Aim 2) | This will assess the mean peak level of esophageal eosinophilia on biopsy (measured in peak eosinophil count - eos/hpf) at the time of recurrence | Symptom recurrence or 1 year after completing the initial 8 week treatment |
| 30872104 | Derived | Dellon ES, Woosley JT, Arrington A, McGee SJ, Covington J, Moist SE, Gebhart JH, Tylicki AE, Shoyoye SO, Martin CF, Galanko JA, Baron JA, Shaheen NJ. Efficacy of Budesonide vs Fluticasone for Initial Treatment of Eosinophilic Esophagitis in a Randomized Controlled Trial. Gastroenterology. 2019 Jul;157(1):65-73.e5. doi: 10.1053/j.gastro.2019.03.014. Epub 2019 Mar 11. |
| BG001 | 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. Fluticasone MDI: Fluticasone multi-dose inhaler - 4 puffs twice daily (880 mcg, twice daily) Placebo slurry: Slurry of sucralose - 4 mL twice daily |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | 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. Fluticasone MDI: Fluticasone multi-dose inhaler - 4 puffs twice daily (880 mcg, twice daily) Placebo slurry: Slurry of sucralose - 4 mL twice daily |
|
|
|
| Primary | Post-treatment Dysphagia Score (Aim 1) | 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. | Posted | Mean | Standard Deviation | score on a scale | 8 weeks |
|
|
|
|
| Secondary | Post-treatment Endoscopic Severity (Aim 1) | 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. | Posted | Mean | Standard Deviation | score on a scale | 8 weeks |
|
|
|
| Secondary | Percentage of Participants With Histologic Response of <15 Eos/Hpf | Percentage with histologic response, with response defined as <15 eos/hpf, will be compared between groups | Posted | Number | Percent responders | 8 weeks |
|
|
|
| Secondary | Post-treatment Symptom Severity (Aim 1) | 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. | Posted | Mean | Standard Deviation | score on a scale | 8 weeks |
|
|
|
| Secondary | Post-treatment Medication Compliance (Aim 1) | 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. | Posted | Number | Percentage of medication used | 8 weeks |
|
|
|
| Secondary | Median Number of Days Until Symptom Recurrence (Aim 2) | 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. | 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. | Posted | Median | Standard Error | Days | Symptom recurrence or 1 year after completing the initial 8 week treatment |
|
|
|
|
| Secondary | Number of Subjects With Histologic Recurrence, Defined as ≥15 Eosinophils Per High-power Field, at Follow-up Endoscopy. | 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. | 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. | Posted | Count of Participants | Participants | Symptom recurrence or 1 year after completing the initial 8 week treatment |
|
|
|
|
| Secondary | Mean Endoscopic Severity Score at Recurrence (Aim 2) | 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. | 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. | Posted | Mean | Standard Deviation | score on a scale | Symptom recurrence or 1 year after completing the initial 8 week treatment |
|
|
|
|
| Secondary | Mean Peak Eosinophil Count (Aim 2) | This will assess the mean peak level of esophageal eosinophilia on biopsy (measured in peak eosinophil count - eos/hpf) at the time of recurrence | 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. | Posted | Mean | Standard Deviation | eosinophils per high-power field | Symptom recurrence or 1 year after completing the initial 8 week treatment |
|
|
|
|
| 0 |
| 65 |
| 0 |
| 65 |
| 10 |
| 65 |
| EG001 | 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. Fluticasone MDI: Fluticasone multi-dose inhaler - 4 puffs twice daily (880 mcg, twice daily) Placebo slurry: Slurry of sucralose - 4 mL twice daily | 0 | 64 | 1 | 64 | 15 | 64 |
| oral candidiasis | Gastrointestinal disorders | Non-systematic Assessment |
|
| sore throat | Gastrointestinal disorders | Non-systematic Assessment |
|
| chest pain | Cardiac disorders | Non-systematic Assessment |
|
| pneumonia | Infections and infestations | Non-systematic Assessment |
|
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| D005759 |
| Gastroenteritis |
| D004802 | Eosinophilia |
| D007960 | Leukocyte Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D000730 | Androstadienes |
| D000736 | Androstenes |
| D000731 | Androstanes |