Clinical trial NCT01222585: Metronidazole Pharmacokinetics (PK) in Premature Infants
Official title: Safety and Pharmacokinetics of Multiple Dose Metronidazole in Premature Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Serious Systemic Infections
Necrotizing Enterocolitis
Keywords: Metronidazole
Neonate
Premature
Sepsis
Necrotizing enterocolitis
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: The Emmes Company, LLC
First posted: 2010-10-18
Enrollment: 24
Sex: ALL
Maximum age (years): 90
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Area Under the Curve at Steady State
timeFrame: 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
measure: Loading Dose Maximum Concentration
timeFrame: 2-5 days of study drug administration
measure: Loading Dose Minimum Concentration
timeFrame: 2-5 days of study drug administration
measure: Multiple Dose Maximum Concentration
timeFrame: 2-5 days of study drug administration
measure: Multiple Dose Minimum Concentration
timeFrame: 2-5 days of study drug administration
measure: Clearance
timeFrame: 2-5 days of study drug administration
measure: Volume of Distribution
timeFrame: 2-5 days of study drug administration
Secondary outcomes:
Other outcomes:
Locations:
city: Orange
country: United States
facility: CHOC Children's
state: California
city: Wichita
country: United States
facility: Wesely Medical Center
state: Kansas
city: Durham
country: United States
facility: Duke University
state: North Carolina
Study officials:
affiliation: Duke University
name: Michael Cohen-wolkowiez, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.