Metronidazole Pharmacokinetics (PK) in Premature Infants

Brief Summary

Official Title: “Safety and Pharmacokinetics of Multiple Dose Metronidazole in Premature Infants”

Yearly in the United States over 500,000 newborns are delivered prematurely. This population is at high risk of catastrophic bowel disease known as necrotizing enterocolitis. Infants with necrotizing enterocolitis are at high risk of death, and survivors are at increased risk of mental retardation. Metronidazole is an antibiotic that is often administered to infants with suspected or confirmed necrotizing enterocolitis. Unfortunately, the appropriate dose of metronidazole in premature infants has not been established and it is likely to be different from older children and adults.

The investigators will investigate the appropriate metronidazole dose in very premature infants by: 1) determining how premature infants eliminate metronidazole from the body and 2) determining the safest and most effective dose of metronidazole in premature infants.

The investigators hypothesis are: 1) The rate of removal of metronidazole will increase with infant maturity and 2) an appropriate metronidazole dosing regimen will result in necessary drug levels to treat bacteria involved in necrotizing enterocolitis.

  • Study Type: Interventional
  • Study Design: Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
  • Study Primary Completion Date: November 2011

Interventions Used in this Clinical Trial

  • Drug: Metronidazole
    • Metronidazole will be administered intravenously to premature infants as a 15 mg/kg loading dose followed by maintenance doses of 7.5 mg/kg every 12 hours for infants with >=14 postnatal days and every 24 hours for infants <14 postnatal days.

Arms, Groups and Cohorts in this Clinical Trial

  • Experimental: Treatment
    • Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours

Outcome Measures for this Clinical Trial

Primary Measures

  • Area Under the Curve at Steady State
    • Time Frame: pre-dose: 30 min; post-dose:10 min, 3-4,6-8, 12-13, 24-25, 36-37, 48-49, 72-73 hours post dose
      Safety Issue?: Yes
  • Loading Dose Maximum Concentration
    • Time Frame: 2-5 days of study drug administration
      Safety Issue?: Yes
  • Loading Dose Minimum Concentration
    • Time Frame: 2-5 days of study drug administration
      Safety Issue?: Yes
  • Multiple Dose Maximum Concentration
    • Time Frame: 2-5 days of study drug administration
      Safety Issue?: Yes
  • Multiple Dose Minimum Concentration
    • Time Frame: 2-5 days of study drug administration
      Safety Issue?: Yes
  • Clearance
    • Time Frame: 2-5 days of study drug administration
      Safety Issue?: Yes
  • Volume of Distribution
    • Time Frame: 2-5 days of study drug administration
      Safety Issue?: Yes

Criteria for Participation in this Clinical Trial

Inclusion Criteria

  • Gestational age <32 weeks at the time of enrollment.
  • Postnatal age <91 days at the time of enrollment.
  • Sufficient venous access to permit administration of study medication.
  • Infant suspected to have a serious infection and from whom a blood culture has been obtained within 96 hours of study entry.

Exclusion Criteria

  • History of anaphylaxis to metronidazole or other nitroimidazole derivatives (e.g., tinidazole).
  • Previous exposure to metronidazole in the week prior to study.
  • Previous participation in the study.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: 90 Days

Are Healthy Volunteers Accepted for this Clinical Trial: No

Clinical Trial Investigator Information

  • Lead Sponsor
    • Michael Cohen-Wolkowiez
  • Collaborator
    • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  • Provider of Information About this Clinical Study
    • Sponsor-Investigator: Michael Cohen-Wolkowiez, Assistant Professor of Pediatrics – Duke University Medical Center
  • Overall Official(s)
    • Michael Cohen-wolkowiez, MD, Principal Investigator, Duke University

Citations Reporting on Results

Cohen-Wolkowiez M, Sampson M, Bloom BT, Arrieta A, Wynn JL, Martz K, Harper B, Kearns GL, Capparelli EV, Siegel D, Benjamin DK Jr, Smith PB; Best Pharmaceuticals for Children Act–Pediatric Trials Network. Determining population and developmental pharmacokinetics of metronidazole using plasma and dried blood spot samples from premature infants. Pediatr Infect Dis J. 2013 Sep;32(9):956-61. doi: 10.1097/INF.0b013e3182947cf8.

Source

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The URL of this page is:
http://clinicaltrialsfeeds.org/clinical-trials/show/NCT01222585