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Budesonide Versus Fluticasone for Treatment of Eosinophilic Esophagitis

This study is currently recruiting participants.
See Contacts and Locations
Verified May 2017 by University of North Carolina, Chapel Hill
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT02019758
First received: December 18, 2013
Last updated: May 15, 2017
Last verified: May 2017
  Purpose

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 Intervention
Eosinophilic Esophagitis Drug: Oral Viscous Budesonide Drug: Fluticasone MDI Drug: Placebo slurry Drug: Placebo inhaler

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Budesonide Versus Fluticasone for Treatment of Eosinophilic Esophagitis

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Histologic effectiveness of viscous budesonide versus fluticasone MDI [ 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 EoE. The mean post-treatment maximum eosinophil count will be compared between the OVB and MDI groups using a two-sample t-test. The pre- and post-treatment counts will also be compared within study groups using a paired t-test.

  • Symptomatic effectiveness of viscous budesonide versus fluticasone MDI [ Time Frame: 2 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, and within groups using a paired t-test.


Secondary Outcome Measures:
  • Symptom recurrence [ Time Frame: Symptom recurrence or 1 year after enrollment ]
    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.

  • Histologic recurrence [ Time Frame: Symptom recurrence or 1 year after enrollment ]
    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.


Other Outcome Measures:
  • Baseline immunohistochemical (IHC) staining and histologic response [ 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.

  • Endoscopic findings of EoE [ Time Frame: 8 weeks ]
    To measure the EoE Endoscopic Reference Score (EREFS) based on esophageal findings: esophageal exudates, rings, edema, furrows, and stricture.

  • Levels of histologic response [ Time Frame: 8 weeks ]
    To measure the levels of histologic response defined as complete responders (< 5 eos/hpf), partial responders (5-14 eos/hpf) and non-responders (≥ 15 eos/hpf).

  • Medication compliance [ Time Frame: 8 weeks ]
    To measure medication compliance by residual OVB slurry left over and the actuation counter on the MDI

  • Baseline immunohistochemical (IHC) staining and other levels of histologic response [ 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 other levels of histologic response (partial response with 5-14 eos/hpf and non-response with ≥15 eos/hpf) in EoE patients treated with topical corticosteroid therapy.


Estimated Enrollment: 200
Study Start Date: October 2014
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 - 1mg/4mL, 4mL 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 - 4mL twice daily
Other Name: Sucralose

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 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.

  Eligibility

Ages Eligible for Study:   16 Years to 80 Years   (Child, Adult, Senior)
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 BID 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02019758

Contacts
Contact: Susan Moist, MPH 919-966-7655 susan_moist@med.unc.edu
Contact: Evan Dellon, MD, MPH evan_dellon@med.unc.edu

Locations
United States, North Carolina
University of North Carolina, Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Susan Moist, MPH    919-966-7655    susan_moist@med.unc.edu   
Contact: Sarah McGee    919-966-4591    smcgee@med.unc.edu   
Principal Investigator: Evan S Dellon, MD, MPH         
Sub-Investigator: Nicholas Shaheen, MD, MPH         
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
  More Information

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 )
Study First Received: December 18, 2013
Last Updated: May 15, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Esophagitis
Eosinophilic Esophagitis
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastroenteritis
Eosinophilia
Leukocyte Disorders
Hematologic Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
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

ClinicalTrials.gov processed this record on September 19, 2017