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Optimal Dosing of Omeprazole in Neonates (OMEPRAZOLE-1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01657578
First received: August 2, 2012
Last updated: October 10, 2012
Last verified: July 2012
  Purpose

"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."


Condition Intervention Phase
Gastroesophageal Reflux Disease (GERD)
Drug: Omeprazole
Phase 2

Study Type: Interventional
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
Official Title: Optimal Dose and Population Pharmacokinetics of Omeprazole in Neonates With Gastroesophageal Reflux Disease (GERD)

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Presence of a normalised control pHmetry Presence of a normalised control pHmetry Presence of a normalised control pHmetry [ Time Frame: 72±24 hours after initiation of omeprazole treatment ] [ Designated as safety issue: No ]
    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:
  • mean number of reflux episodes per hour [ Time Frame: 72±24 hours after initiation of omeprazole treatment ] [ Designated as safety issue: No ]
    mean number of reflux episodes per hour

  • duration of the longest reflux episode [ Time Frame: 72±24 hours after initiation of omeprazole treatment ] [ Designated as safety issue: No ]
    duration of the longest reflux episode

  • plasma concentrations of omeprazole and its metabolite, hydroxyl-omeprazole [ Time Frame: H0.5 and H4 or between H4 and H12 after the first administration of omeprazole ] [ Designated as safety issue: No ]
    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

  • changes in salivary pH monitoring [ Time Frame: just before and 3 hours after a meal Under treatment period ] [ Designated as safety issue: No ]
    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 [ Time Frame: 96±24 hours after initiation of omeprazole treatment ] [ Designated as safety issue: Yes ]
    changes in biological parameters


Enrollment: 55
Study Start Date: June 2007
Study Completion Date: February 2012
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: neonates of less than 32 weeks gestational age
omeprazole
Drug: Omeprazole
administration of Omeprazole
Other Name: administration of Omeprazole
Experimental: neonates born between 32 and 35 weeks of GA
omeprazole
Drug: Omeprazole
administration of Omeprazole
Other Name: administration of Omeprazole
Experimental: neonates of more than 36 weeks of GA
omeprazole
Drug: Omeprazole
administration of Omeprazole
Other Name: administration of Omeprazole

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

Ages Eligible for Study:   35 Weeks and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01657578

Locations
France
Hospital Robert Debre
Paris, France, 75019
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Evelyne Jacqz-Aigrain, MD, PhD Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01657578     History of Changes
Other Study ID Numbers: P 051043, 2006-005335-16
Study First Received: August 2, 2012
Last Updated: October 10, 2012
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
neonates
reflux disease
population pharmacokinetics, omeprazole

Additional relevant MeSH terms:
Gastroesophageal Reflux
Deglutition Disorders
Digestive System Diseases
Esophageal Diseases
Esophageal Motility Disorders
Gastrointestinal Diseases
Omeprazole
Anti-Ulcer Agents
Enzyme Inhibitors
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Proton Pump Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014