Clinical trial NCT02069847: Prospective Evaluation of Budesonide for Prevention of Esophageal Strictures After Endotherapy
Official title: Prospective Evaluation of the Clinical Utility of Budesonide for the Prevention of Esophageal Strictures After Endotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Esophageal Stricture
Keywords: Esophageal stricture formation
Endoscopic mucosal resection
Endoscopic submucosal dissection
Budesonide
Radical endoscopic mucosal resection
EMR
ESD
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2014-02-24
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Surgery has been historically the mainstay treatment for advanced pre-malignant lesions and early esophageal cancers. However, esophagectomy is associated with significant morbidity and mortality. With the advance of therapeutic endoscopy, there has been a growing interest and application of endoscopic resection and mucosal ablative techniques for the treatment of these diseases. Esophageal stricture (ES) formation has become an increasingly recognized complication of extensive endoscopic mucosal ablation and/or resection. The resultant symptomatic stricture development can significantly impair a patient's quality of life. Endoscopic therapy of esophageal strictures with balloon dilation and/or local steroid injection is invasive, costly, and associated with the potential risk of perforation. Recently, oral corticosteroids have been introduced for the prevention of esophageal stricture after endoscopic submucosal dissection.

Budesonide is a synthetic steroid with topical anti-inflammatory properties and high first-pass metabolism; thus, potentially less systemic absorption and side effects.

Hypothesis: Oral budesonide prevents esophageal stricture formation in patients who underwent radical endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) for advanced premalignant esophageal lesions or superficial esophageal cancers.

Detailed description: Esophageal stricture (ES) formation is a widely recognized adverse event of radical EMR and ESD. Indeed, ES is the most common complication of radiofrequency ablation (RFA) for Barrett's esophagus (BE), with a reported incidence ranging from 5% to 12%. A single-center retrospective study reported ES formation in 67% of 73 patients with EMR of at least 50% of their esophageal circumference. Similarly, the incidence of ES development after ESD is between 70-90% when the mucosal defect involves more than three-quarters of the esophageal circumference. In aggregate, the extent of the esophageal mucosal defect following endotherapy appears to be the most consistent predictor of ES formation. Prevention of ES development following endotherapy can significantly improve a patient's quality of life and possibly reduce the potential risks and costs associated with treatment of ES with repeated endoscopic balloon dilations (EBD). Glucocorticoids have been evaluated as a potential preventive therapy for ES based on their anti-inflammatory properties and inhibitory effects on collagen deposition. Oral prednisolone has been shown to be effective as a preventive strategy for ES formation. However, prolonged use of systemic oral steroids can be associated with multiple adverse effects.

Budesonide is a synthetic steroid with topical anti-inflammatory properties and high first-pass metabolism; thus, potentially less systemic absorption and side effects. Most recently Mayo Clinic Rochester developed a new budesonide capsule formulation. Alike viscous budesonide the budesonide capsule can be opened and the powder can be mixed with honey or pancake syrup. A similar formulation is currently used in pilot studies for treatment of eosinophilic esophagitis. The advantage of budesonide capsule is the improve taste in comparison to viscous budesonide originating from budesonide respules which is unpalatable.

Study aims:

1. The aim of this study is to prospectively record our experience with budesonide for the prevention of esophageal stricture formation after endotherapy (mucosal resection, submucosal dissection) as part of routine medical care.
2. The data will be compared with outcomes with well-annotated historical controls that underwent similar procedure with similar follow up but without budesonide exposure.
3. If sufficient efficacy is seen, these data will be used to plan a prospective controlled clinical trial. All patients in the study group will receive standard medical care and no experimental interventions will be performed.

Eligibility criteria: Inclusion Criteria:

* Age 18 years or older
* Diagnosis of esophageal lesion treated with ESD or EMR which involves ≥ 50% of the esophageal circumference.

Exclusion Criteria:

* Locally advanced disease
* Prior esophageal surgery
* Participation in another research protocol that could interfere or influence the outcome measures of the present study.
* The subject or legal representative is unable/unwilling to give informed consent. (study group)
* Medications or conditions for which there is a contraindication to use of budesonide (see pharmacology section below)
* Concomitant use of systemic steroids or other immune suppressive medication for a different condition 9. Pregnant women

Primary outcomes:
measure: Dysplasia in Barrett Esophagus (BE)
timeFrame: 3 months
Secondary outcomes:
measure: Rate of Esophageal Stricture
timeFrame: 3 months
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
Study officials:
affiliation: Mayo Clinic
name: Michael Wallace, MD
role: PRINCIPAL_INVESTIGATOR
References: