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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

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.


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Study Type : Interventional  (Clinical Trial)
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 : January 1, 2015
Actual Primary Completion Date : May 2018
Actual Study Completion Date : April 2019


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 Name: Pulmicort

Drug: Placebo inhaler
Placebo inhaler - 4 puffs twice daily
Other Name: 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 Name: Flovent

Drug: Placebo slurry
Slurry of sucralose - 4 mL twice daily
Other Name: Sucralose




Primary Outcome Measures :
  1. Post-treatment Maximum Eosinophil Count (Aim 1) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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. Symptom Recurrence (Aim 2) [ Time Frame: Symptom recurrence or 1 year after completing the initial 8 week treatment ]
    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.

  6. Histologic Recurrence (Aim 2) [ Time Frame: 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 proportion of subjects with ≥15 eos/hpf at follow-up endoscopy in each group will be compared using chi-square.

  7. Endoscopic Severity at Recurrence (Aim 2) [ Time Frame: Symptom recurrence or 1 year after completing the initial 8 week treatment ]
    Measurement of endoscopic severity, using the validated EREFS measure, at the time of recurrence

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


Other Outcome Measures:
  1. Baseline Immunohistochemical (IHC) Staining and Histologic Response (Aim 3) [ Time Frame: Enrollment (Day 1) ]

    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.




Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02019758


Locations
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United States, North Carolina
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
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Principal Investigator: Evan S Dellon, MD, MPH University of North Carolina, Chapel Hill
  Study Documents (Full-Text)

Documents provided by University of North Carolina, Chapel Hill:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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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 Posted: December 24, 2013    Key Record Dates
Results First Posted: April 26, 2019
Last Update Posted: May 15, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Leukocyte Disorders
Hematologic Diseases
Immune System Diseases
Esophagitis
Eosinophilic Esophagitis
Gastroenteritis
Eosinophilia
Hypersensitivity, Immediate
Hypersensitivity
Fluticasone
Budesonide
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists