Metronidazole Pharmacokinetics (PK) in Premature Infants

NCT01222585 | Completed Phase 1 Results DMC

• 2 other identifiers: Pro00024571HHSN27500003I
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Serious Systemic Infections; Necrotizing Enterocolitis

Keywords

Metronidazole; Neonate; Premature; Sepsis; Necrotizing enterocolitis

Outcome Measures

Primary Outcomes (7)

• Area Under the Curve at Steady State

  Area under the curve at steady state (AUCss)

  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

• Loading Dose Maximum Concentration

  Loading Dose Maximum concentration (Cmax)

  2-5 days of study drug administration

• Loading Dose Minimum Concentration

  Loading Dose Minimum Concentration (mg/L)

  2-5 days of study drug administration

• Multiple Dose Maximum Concentration

  Multiple Dose Maximum Concentration (mg/L)

  2-5 days of study drug administration

• Multiple Dose Minimum Concentration

  Multiple Dose Minimum Concentration (mg/L)

  2-5 days of study drug administration

• Clearance

  Clearance (L/h/kg)

  2-5 days of study drug administration

• Volume of Distribution

  Volume of Distribution (L/kg)

  2-5 days of study drug administration

Study Arms (1)

Treatment

EXPERIMENTAL

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

Drug: Metronidazole

Interventions

Metronidazole DRUG

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.

Also known as: Flagyl

Treatment

Eligibility Criteria

• Age: Up to 90 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Michael Cohen-Wolkowiez: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• The Emmes Company, LLC: collaborator

Study Sites (3)

CHOC Children's

Orange, California, 92868, United States

Location

Wesely Medical Center

Wichita, Kansas, 67214, United States

Location

Duke University

Durham, North Carolina, 27715, United States

Location

Related Publications (1)

• 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.

  PMID: 23587979 RESULT

MeSH Terms

Conditions

Enterocolitis, Necrotizing; Premature Birth; Sepsis

Interventions

Metronidazole

Condition Hierarchy (Ancestors)

Enterocolitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Michael Cohen-Wolkowiez, MD
• Organization: Duke Clinical Research Institute

michael.cohenwolkowiez@dm.duke.edu

919668-8812

Study Officials

• Michael Cohen-wolkowiez, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Study Record Dates

• First Submitted: October 6, 2010
• First Posted: October 18, 2010
• Study Start: January 1, 2011
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: February 6, 2014
• Results First Posted: December 18, 2013

Record last verified: 2014-01

Locations

US (3)