Budesonide Versus Fluticasone for Treatment of Eosinophilic Esophagitis

NCT02019758 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: 13-4047R01DK101856
• Study Type: interventional
• Target: 129
• Locations: 1 country
• Sites: 1

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

Conditions

Eosinophilic Esophagitis

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (8)

• Post-treatment Endoscopic Severity (Aim 1)

  8 weeks

• Percentage of Participants With Histologic Response of <15 Eos/Hpf

  8 weeks

• Post-treatment Symptom Severity (Aim 1)

  8 weeks

• Post-treatment Medication Compliance (Aim 1)

  8 weeks

• Median Number of Days Until Symptom Recurrence (Aim 2)

  Symptom recurrence or 1 year after completing the initial 8 week treatment

Study Arms (2)

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.

Drug: Oral Viscous Budesonide; Drug: Placebo inhaler

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.

Drug: Fluticasone MDI; Drug: Placebo slurry

Interventions

Oral Viscous Budesonide DRUG

Oral Viscous Budesonide - 1 mg/4 mL, 4 mL of slurry twice daily

Also known as: Pulmicort

Oral Viscous Budesonide (OVB)

Fluticasone MDI DRUG

Fluticasone multi-dose inhaler - 4 puffs twice daily (880 mcg, twice daily)

Also known as: Flovent

Active Fluticasone MDI

Placebo slurry DRUG

Slurry of sucralose - 4 mL twice daily

Also known as: Sucralose

Active Fluticasone MDI

Placebo inhaler DRUG

Placebo inhaler - 4 puffs twice daily

Also known as: Placebo

Oral Viscous Budesonide (OVB)

Eligibility Criteria

• Age: 16 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• Pregnancy
• Inability to read or understand English

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

University of North Carolina, Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (3)

• 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.

  PMID: 33009060 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.

  PMID: 31499249 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.

  PMID: 30872104 DERIVED

MeSH Terms

Conditions

Eosinophilic Esophagitis

Interventions

Budesonide; Fluticasone; trichlorosucrose

Condition Hierarchy (Ancestors)

Esophagitis; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Androstadienes; Androstenes; Androstanes

Results Point of Contact

• Title: Evan S. Dellon, MD MPH
• Organization: University of North Carolina at Chapel Hill

edellon@med.unc.edu

919-966-2513

Study Officials

• Evan S Dellon, MD, MPH

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2013
• First Posted: December 24, 2013
• Study Start: January 1, 2015
• Primary Completion: May 1, 2018
• Study Completion: April 1, 2019
• Last Updated: April 27, 2020
• Results First Posted: April 26, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)