Optimal Dosing of Omeprazole in Neonates

Phase 2

Completed

• Conditions: Gastroesophageal Reflux Disease (GERD)
• Interventions: Drug: Omeprazole

• Registration Number: NCT01657578
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

"The principal aim of this trial is to determine the minimum effective dose of omeprazole in neonates with GERD objectively diagnosed by a 24-h intra-oesophageal pH monitoring (pHmetry), to obtain a short-term efficacy in the pHmetry of control performed 72 hrs ± 24 after initiation of omeprazole.

The secondary objectives of the study were: (1) to assess the efficacy of omeprazole upon other pHmetry parameters, (2) to characterize the population pharmacokinetics and pharmacogenetics of omeprazole, (3) to evaluate the effect of omeprazole upon oro-pharyngeal pH monitoring and (4) to assess the short-term safety of use of omeprazole in neonates."

Detailed Description

"Omeprazole is a proton pump inhibitor increasingly prescribed in the neonatal population for gastroesophageal reflux disease (GERD) complicated or not by the presence of esophagitis. Although extensively evaluated in adults, optimal dosing schemas, efficacy and safety have not been determined in the neonatal population where its prescription remains off-label. The study is a double blind trial that was designed using a Bayesian sequential analysis approach. The principle of this approach is to identify the adequate drug dosage to obtain a level of efficacy as close as possible to a predetermined target level of efficacy in the population. In this study, five different dosages of omeprazole are tested (1, 1,5, 2, 2,5, 3 mg/kg/day) and a target probability of successful treatment of 95% has been chosen. To assess the influence of gestational age on omeprazole's efficacy, analysis was stratified on 3 groups: (1) neonates of less than 32 weeks gestational age (GA), (2) neonates born between 32 and 35 weeks of GA, (3) neonates of more than 36 weeks of GA.

A total maximum number of 90 neonates is expected to be included (30 neonates per group).

Patients' participation in the study ends after completion of the pHmetry of control that is 72 ±24 hours after omeprazole initiation.

Patients in the study will all benefit for the management of their GERD from non-pharmacological therapies such as adequate positioning and use of available thickening agents for formula The only pharmacologic agent authorised during study for treating GERD is omeprazole. All other available GERD treatments will not be prescribed."

Study Timeline

• Study Start: 2007-06
• Primary Completion: 2010-12
• Study Completion: 2012-02
• Status Verified: 2012-07
• Study First Submitted: 2012-08-02
• Study First Submitted QC: 2012-08-03
• Study First Posted: 2012-08-06
• Last Update Submitted: 2012-10-10
• Last Update Posted: 2012-10-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 55

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
neonates of more than 36 weeks of GA	Omeprazole	omeprazole
neonates born between 32 and 35 weeks of GA	Omeprazole	omeprazole
neonates of less than 32 weeks gestational age	Omeprazole	omeprazole

Primary Outcome Measures

Name	Time	Method
Presence of a normalised control pHmetry Presence of a normalised control pHmetry Presence of a normalised control pHmetry	72±24 hours after initiation of omeprazole treatment	Normalised control pHmetry is defined by a reflux index (duration that the recorded intra-oesophageal pH is less than 4.0, expressed as a percentage of the total duration of pH monitoring) of less than 5%

Secondary Outcome Measures

Name	Time	Method
plasma concentrations of omeprazole and its metabolite, hydroxyl-omeprazole	H0.5 and H4 or between H4 and H12 after the first administration of omeprazole	Plasma concentrations of omeprazole and its metabolite, hydroxyl-omeprazole, After the first administration of omeprazole, blood will be collected either between H0.5 and H4 or between H4 and H12 or both
mean number of reflux episodes per hour	72±24 hours after initiation of omeprazole treatment	mean number of reflux episodes per hour
duration of the longest reflux episode	72±24 hours after initiation of omeprazole treatment	duration of the longest reflux episode
changes in salivary pH monitoring	just before and 3 hours after a meal Under treatment period	changes in salivary pH monitoring Without treatment period: just before and 3 hours after a meal Under treatment period: just before and just after the insertion of the pHmetry catheter
changes in biological parameters	96±24 hours after initiation of omeprazole treatment	changes in biological parameters

Trial Locations

Locations (1)

Hospital Robert Debre; 🇫🇷 Paris, France