Budesonide Following Endoscopic Dilatation of Esophageal Strictures in Children.

Official title

Single-blinded, Randomized Controlled Trial of Budesonide Following Endoscopic Dilatation of Esophageal Strictures in Children.

Overview

Endoscopic balloon dilatation (EBD) is a common therapeutic procedure performed for esophageal strictures. While the etiologies of esophageal strictures are numerous - including congenital strictures, caustic injuries and eosinophilic esophagitis (EoE) -anastomotic strictures following esophageal atresia and trachea-esophageal fistula repairs is reported as the most frequent cause in children. Stricture dilatation is usually performed under direct endoscopic vision, with graduated balloon dilatation, utilizing increasing balloon diameters deployed until reaching a pre-determined, age-based, dilatation target. Balloon dilatation is repeated every 2-4 weeks until the target is reached. Success is defined as prolonged restoration of effective swallow with no dysphagia or dietary restrictions. Dilatation is repeated if clinical resolution is not obtained, or if symptoms return after initial resolution. In children, a stricture is considered refractory when the age-appropriate esophageal lumen is not achieved with five dilatations within 5 months, or if despite ≥7 dilatations overall an age-appropriate esophageal lumen was not maintained. Several interventions have been studied to improve the efficacy of balloon dilatation, including injecting corticosteroids at the dilatation site, topical Mitomycin C following dilatation, or pre-dilatation endoscopic incisions of the anastomotic scar tissue. All these interventions are performed endoscopically at the time of the dilatation, require advanced endoscopic skills and may potentially have associated additional risk. In this study the investigators aim to test the efficacy and safety of topical budesonide gel following EBD for anastomotic esophageal strictures in a single-blinded, randomized controlled study of children.

Detailed description

This single-blinded randomized controlled trial aims to prospectively evaluate the efficacy of swallowed budesonide gel following EBD of esophageal strictures. Due to the variable nature of congenital strictures and the more disparate features of caustic and EoE strictures, the study is limited to simple strictures at the site of anastomoses.

Patients will be assessed as per the ESPGHAN and NASPGHAN guidelines for the evaluation and treatment of children with esophageal atresia-trachoesophageal fistula, with gastroscopy performed either at one-year of age or earlier in symptomatic patients with dysphagia.

Patients in whom an anastomotic esophageal stricture is identified, dilatations will be performed as per physician discretion regarding diameter and timing of dilatations, guided predominantly by the aforementioned treatment guidelines. Patients will be randomly assigned to either budesonide gel (1mg/8mL) 250mcg orally twice daily for 12 weeks from the first dilatation, or to standard of care with no oral budesonide. Treating physician will be blinded to patient treatment Esophageal stricture characteristics will be recorded at each endoscopy with pre-dilation diameter (estimated based on relative size to pre-measured biopsy forceps placed in proximity to the stricture) and maximal dilatation diameter at each session.

Patients will be assessed clinically routinely at 1, 2, 3, 4 and 6 months following initial dilatation, and at 6 months following the last dilatation in the series, during which dysphagia symptom score and patient weight will be assessed.

Success is defined as restoration of effective swallow with no dysphagia or age-appropriate dietary restrictions for 3 months. Outcome measures will include number of EBD procedures until success is achieved, as well as the rate of restenosis (defined clinically as a dysphagia score of ≥1) after success is achieved 6 months following the last EBD procedure.

The primary aim of the study is to assess the number of dilatations required to achieve clinical success between the treatment and placebo group. Secondary aims include rate of refractory strictures, restenosis rate, dysphagia score, patient weight and safety (including cortisol suppression, oral or esophageal fungal infection, and anthropomorphics).

Interventions

• Drug Budesonide intervention
  Patients will receive budesonide gel (1mg/8mL) 250mcg orally twice daily for 12 weeks from the first dilatation.

Primary outcome measures

• The number of EBD procedures required to achieve clinical success. [Time frame: From the first dilation up to 6 months after the initial dilation.]

Secondary outcome measures (6)

• Restenosis rate 6 months after last EBD performed [Time frame: Up to 6 months after the last dilation.]
• Rate of refractory strictures [Time frame: Up to 5 months from the initial dilatation, or until the 7th dilatation, whichever occurs first.]
• Patient Weight [Time frame: Up to 6 months after the last dilation.]
• Dysphagia score [Time frame: From baseline until 6 months following the last dilation.]
• Pre-dilatation stricture diameter at each procedure [Time frame: From baseline until final dilation, on average 6 months following the first.]
• Procedure complication rate [Time frame: From the first dilation through 6 months after the final dilation.]

Eligibility criteria

Inclusion criteria

• Infants and children < 12 years old with an anastomotic esophageal stricture following repair of congenital esophageal atresia / tracheoesophageal fistula
• Dysphagia score ≥1
• Parental consent

Exclusion criteria

• Additional stricture/s besides anastomotic stricture eg. Congenital stricture
• Complicated stricture - including length >2cm, significant angulation or irregularity
• Neurological impairment or other cause of expected limitation to oral intake
• Previous anastomotic dilatations
• Complicated surgical course including need for re-operation, re-fistularization or surgical anastomotic leak
• Suspected or verified thoracic vascular anomaly affecting esophageal patency or function
• Verified co-diagnosis of eosinophilic esophagitis
• Any contraindication to EBD according to treating physician's planned treatment course

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Israel · 1 center

• Shaare Zedek Medical Centre — Jerusalem

Identifiers

NCT: NCT07560462 · Budesonide following EBD

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗