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Phase 1 Intravenous Citrulline for the Prevention of Bronchopulmonary Dysplasia in Preterm Infants

Phase 1
Withdrawn
Conditions
Bronchopulmonary Dysplasia
Registration Number
NCT00742534
Lead Sponsor
Vanderbilt University
Brief Summary

Premature infants are at risk for developing bronchopulmonary dysplasia (BPD). L-citrulline may decrease that risk, but we do not know the safety or dose of this drug for use in premature babies. The purpose of this study is to determine the safety and optimal dose of intravenous L-citrulline in premature infants.

Detailed Description

This is a prospective phase I study of the safety, pharmacokinetics, and optimal dose of intravenously administered L-citrulline in premature infants born at 24 to 29 weeks estimated gestational age (EGA) and who are at risk for bronchopulmonary dysplasia (BPD). This is a classic dose escalation using initial doses of 10 mg/kg of intravenous citrulline and advancing the dose by 10 mg/kg every 3 patients for a target peak plasma citrulline concentration of 100 umol/L. These infants will undergo intense hemodynamic monitoring and have intermittent blood sampling to determine levels of amino acids and nitric oxide metabolites. From this, we will determine citrulline pharmacokinetics including half life, clearance, and volume of distribution. Intravenous L-citrulline will be provided by Asklepion Pharmaceuticals and mixed by the Investigational Drug Service of the Vanderbilt Hospital Clinical Pharmacy. The study will be monitored closely by a data safety monitoring board (DSMB) consisting of clinicians not involved with this study.

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
Inclusion Criteria
  • 24-29 Weeks Gestation
  • Respiratory Distress requiring intubation and mechanical ventilation or positive pressure oxygen at 24 hours of life
  • Parents willing and able to sign consent
Exclusion Criteria
  • Congenital malformation
  • Suspected genetic or metabolic syndrome
  • Surgical condition
  • Life expectancy < 24 hours
  • Pre-existing, sustained hypotension
  • Birth weight < 500 grams
  • Any condition which, in the opinion of the investigator, will interfere with the study objectives.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Primary Outcome Measures
NameTimeMethod
Pharmacokinetics and dose finding in preterm infants with BPDSurrounding Dose
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Monroe Carell Jr. Children's Hospital at Vanderbilt

🇺🇸

Nashville, Tennessee, United States

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