Oral Viscous Budesonide in Anastomotic Stricture After Esophageal Atresia Repair (OVB in EA)

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to perform a multicentre, prospective, randomized, placebo controlled, double-blinded study to demonstrate the potential and beneficial effects of OVB in the prevention of recurrence of anastomotic stricture in children operated for esophageal atresia with an anastomotic stricture.

Official Title
-----------------
A Multicentre, Prospective, Randomized, Placebo Controlled, Double-blinded Study to Demonstrate Potential and Beneficial Effects of Oral Viscous Budesonide (OVB) in the Prevention of Recurrence of Anastomotic Stricture in Children Operated on for Esophageal Atresia With Recurrent Anastomotic Strictures

Conditions
-----------------
Esophageal Atresia, Anastomotic Stenosis

Intervention / Treatment
-----------------
* Drug: Budesonide Oral
* Drug: Placebos


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Children aged > 1 month to 3 years Operated for an esophageal atresia of all types except pure TEF. Presence of an anastomotic stricture defined according to experts recommendations : a relative esophageal narrowing at the level of the anastomosis, demonstrated by a contrast study and/or an endoscopy with significant functional impairment and associated symptoms requiring dilation. Symptoms include: feeding or swallowing difficulties, coughing and choking during feeds, food impaction, regurgitation/vomiting of undigested food, drooling. In very young patients: apnea and food refusal. Receiving an ongoing treatment by PPI 1 to 2 mg/kg die Informed parental consent Exclusion Criteria: Known immune deficiency Acute respiratory or intestinal infection Severe respiratory, cardiac or neurological condition precluding OVB or placebo swallowing Child fed exclusively via nasogastric tube or gastrostomy Absence of parental consent

Ages Eligible for Study
-----------------
Minimum Age: 1 Month
Maximum Age: 3 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Budesonide<br>Oral viscous budesonide will be given in apple sauce according to body weight at inclusion: < 10 kg: 250 mcg BID in 5 ml apple sauce 10 kg to <15 kg: 500 mcg BID in 5 ml apple sauce >15 kg: 1000 mcg BID in 5 ml apple sauce | Drug: Budesonide Oral<br>* The subjects will be included at time of the first dilation for an anastomotic stricture. Basal physical exam and clinical evaluation (weight and height, dysphagia score, gastroesophageal reflux, feeding problems, respiratory symptoms, other symptoms). Randomization will be conducted by centre. Because long gap esophageal atresia, high tension anastomosis and history of anastomotic leak are reported as risk factors for occurrence of anastomotic strictures, a stratification at randomization will be performed according to these criteria in each centre. OVB or placebo will be given by the parents and started the day of the dilation at the first meal after recovering of the dilation and anesthesia. Parents will be asked to bring the empty caps which will be counted for assessment of compliance.<br>|
| Placebo Comparator: Placebo<br>Placebo: 5 ml apple sauce BID plus 1 mL saline | Drug: Placebos<br>* Apple Sauce 5 mL+ 1 mL saline<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of dilations needed after randomization (beginning of treatment) | number of dilations needed after randomization (beginning of treatment) | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients needing dilation after randomization (beginning of treatment) | Number of patients needing dilation after randomization (beginning of treatment) | 12 months | 
| Number of patients needing more than 3 dilations after randomization | Number of patients needing more than 3 dilations after randomization | 12 months | 
| Mean time to further dilation | Mean time to further dilation | 12 months | 
| Number of patients treated with an adjuvant therapy | Number of patients treated with an adjuvant therapy | 12 months | 
| Ability to tolerate normal food for age | Ability to tolerate normal food for age | 12 months | 
| Dysphagia score | Dysphagia score | 12 months | 
| Quantification of the anastomostic stricture by the Stricture index (SI) calculated on barium swallow at 12 months of age | Quantification of the anastomostic stricture by the Stricture index (SI) calculated on barium swallow at 12 months of age | 12 months | 
| Side effects/Adverse events | Side effects/Adverse events | 12 months |