Dose-finding study of omeprazole on gastric pH in neonates with gastro-esophageal acid reflux using a bayesian sequential approach

Abstract

Objective Proton pump inhibitors are frequently administered on clinical symptoms in neonates but benefit remains controversial. Clinical trials validating omeprazole dosage in neonates are limited. The objective of this trial was to determine the minimum effective dose (MED) of omeprazole to treat pathological acid reflux in neonates using reflux index as surrogate marker. Design Double blind dose-finding trial with continual reassessment method of individual dose administration using a Bayesian approach, aiming to select drug dose as close as possible to the predefined target level of efficacy (with a credibility interval of 95%). Setting Neonatal Intensive Care unit of the Robert Debré University Hospital in Paris, France. Patients Neonates with a postmenstrual age ô 35 weeks and a pathologic 24-hour intra-esophageal pH monitoring defined by a reflux index ô 5% over 24 hours were considered for participation. Recruitment was stratified to 3 groups according to gestational age at birth. Intervention Five preselected doses of oral omeprazole from 1 to 3 mg/kg/day.