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Metronidazole Pharmacokinetics (PK) in Premature Infants (PTN_METRO)

This study has been completed.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
The EMMES Corporation
Information provided by (Responsible Party):
Michael Cohen-Wolkowiez, Duke University Medical Center Identifier:
First received: October 6, 2010
Last updated: January 7, 2014
Last verified: January 2014

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.

Condition Intervention Phase
Serious Systemic Infections
Necrotizing Enterocolitis
Drug: Metronidazole
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety and Pharmacokinetics of Multiple Dose Metronidazole in Premature Infants

Resource links provided by NLM:

Further study details as provided by Duke University:

Primary Outcome 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 ]
    Area under the curve at steady state (AUCss)

  • Loading Dose Maximum Concentration [ Time Frame: 2-5 days of study drug administration ]
    Loading Dose Maximum concentration (Cmax)

  • Loading Dose Minimum Concentration [ Time Frame: 2-5 days of study drug administration ]
    Loading Dose Minimum Concentration (mg/L)

  • Multiple Dose Maximum Concentration [ Time Frame: 2-5 days of study drug administration ]
    Multiple Dose Maximum Concentration (mg/L)

  • Multiple Dose Minimum Concentration [ Time Frame: 2-5 days of study drug administration ]
    Multiple Dose Minimum Concentration (mg/L)

  • Clearance [ Time Frame: 2-5 days of study drug administration ]
    Clearance (L/h/kg)

  • Volume of Distribution [ Time Frame: 2-5 days of study drug administration ]
    Volume of Distribution (L/kg)

Enrollment: 24
Study Start Date: January 2011
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours
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.
Other Name: Flagyl


Ages Eligible for Study:   up to 90 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.
  Contacts and Locations
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Please refer to this study by its identifier: NCT01222585

United States, California
CHOC Children's
Orange, California, United States, 92868
United States, Kansas
Wesely Medical Center
Wichita, Kansas, United States, 67214
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27715
Sponsors and Collaborators
Michael Cohen-Wolkowiez
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
The EMMES Corporation
Principal Investigator: Michael Cohen-wolkowiez, MD Duke University
  More Information

Responsible Party: Michael Cohen-Wolkowiez, Assistant Professor of Pediatrics, Duke University Medical Center Identifier: NCT01222585     History of Changes
Other Study ID Numbers: Pro00024571
HHSN27500003I ( Other Grant/Funding Number: NICHD )
Study First Received: October 6, 2010
Results First Received: July 23, 2013
Last Updated: January 7, 2014

Keywords provided by Duke University:
Necrotizing enterocolitis

Additional relevant MeSH terms:
Premature Birth
Enterocolitis, Necrotizing
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Systemic Inflammatory Response Syndrome
Pathologic Processes
Anti-Infective Agents
Antiprotozoal Agents
Antiparasitic Agents processed this record on May 22, 2017