Optimal Dosing of Omeprazole in Neonates
Information source: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Gastroesophageal Reflux Disease (GERD)
Intervention: Omeprazole (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Assistance Publique - Hôpitaux de Paris Official(s) and/or principal investigator(s): Evelyne Jacqz-Aigrain, MD, PhD, Principal Investigator, Affiliation: Assistance Publique - Hôpitaux de Paris
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."
Clinical Details
Official title: Optimal Dose and Population Pharmacokinetics of Omeprazole in Neonates With Gastroesophageal Reflux Disease (GERD)
Study design: Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Presence of a normalised control pHmetry Presence of a normalised control pHmetry Presence of a normalised control pHmetry
Secondary outcome: mean number of reflux episodes per hourduration of the longest reflux episode plasma concentrations of omeprazole and its metabolite, hydroxyl-omeprazole changes in salivary pH monitoring changes in biological parameters
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."
Eligibility
Minimum age: 35 Weeks.
Maximum age: N/A.
Gender(s): Both.
Criteria:
INCLUSION CRITERIA:
- Full-term neonates or preterm neonates with a postmenstrual age >/= 35 weeks
- Presenting abnormal pHmetry (= percentage of the entire record that intra-oesophageal
pH is <4 is superior or equal to 5%)
- Patient must receive discontinuous oral feedings
- If proton pump inhibitors or other pharmacologic antireflux therapies had already
commenced, these had to be withdrawn 7 days before baseline recordings
- In-patient in Neonatal Intensive Care Unit or Neonatology Unit of the Robert Debré
University Hospital
- Both parents sign written informed consent form
- Affiliated to social security
EXCLUSION CRITERIA:
- Patients under proton pump inhibitors (PPI) treatment or that have discontinued PPI
treatment less than 7 days before inclusion
- Patients with acute gastrointestinal disease (diarrhoea)
- Patients than present leucopenia or thrombocytopenia (value half the normal value for
age)
- Patients that present aspartate and alanine aminotransferase values twice the upper
limit of normal
- Patients that present renal and hepatic failure
- Newborns presenting galactosemia, glucose-galactose malabsorption, deficiency in
lactase enzymes
- Co-administration of atazanavir and ritonavir
- Patients allergic to omeprazole or to any other ingredients in the medicine
Locations and Contacts
Hospital Robert Debre, Paris 75019, France
Additional Information
Starting date: June 2007
Last updated: October 10, 2012
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