Metronidazole Pharmacokinetics (PK) in Premature Infants

Necrotizing Enterocolitis Clinical Trial

— PTN_METRO  

Official title:

Safety and Pharmacokinetics of Multiple Dose Metronidazole in Premature Infants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01222585
• Other study ID #: Pro00024571
• Secondary ID: HHSN27500003I
• Status: Completed
• Phase: Phase 1
• First received: October 6, 2010
• Last updated: January 7, 2014
• Start date: January 2011
• Est. completion date: November 2011

Study information

• Verified date: January 2014
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: November 2011
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 90 Days

Eligibility

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.

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Enterocolitis
• Enterocolitis, Necrotizing
• Necrotizing Enterocolitis
• Sepsis
• Serious Systemic Infections

Intervention

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.

Locations

Country	Name	City	State
United States	Duke University	Durham	North Carolina
United States	CHOC Children's	Orange	California
United States	Wesely Medical Center	Wichita	Kansas

Sponsors (3)

Lead Sponsor	Collaborator
Michael Cohen-Wolkowiez	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), The EMMES Corporation

Country where clinical trial is conducted

United States, 

References & 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 pharmacok — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	Loading Dose Maximum Concentration	Loading Dose Maximum concentration (Cmax)	2-5 days of study drug administration	Yes
Primary	Loading Dose Minimum Concentration	Loading Dose Minimum Concentration (mg/L)	2-5 days of study drug administration	Yes
Primary	Multiple Dose Maximum Concentration	Multiple Dose Maximum Concentration (mg/L)	2-5 days of study drug administration	Yes
Primary	Multiple Dose Minimum Concentration	Multiple Dose Minimum Concentration (mg/L)	2-5 days of study drug administration	Yes
Primary	Clearance	Clearance (L/h/kg)	2-5 days of study drug administration	Yes
Primary	Volume of Distribution	Volume of Distribution (L/kg)	2-5 days of study drug administration	Yes