A Phase 1 interventional study of Metronidazole in Serious Systemic Infections and Necrotizing Enterocolitis, sponsored by Michael Cohen-Wolkowiez. Completed at 3 sites in United States. Open to participants aged Up to 90 Days. Per ClinicalTrials.gov, last updated 2014-02-06.
Sponsored by Michael Cohen-Wolkowiez · Phase 1, Interventional, and Treatment
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.
1,899 studies on the registry are indexed under Sepsis; 462 are open to participants now.
This study's enrollment of 24 is below the median of 105 across 896 interventional studies indexed under Sepsis.
Browse Sepsis studies →Michael Cohen-Wolkowiez is the lead sponsor of 5 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
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.
Also known as: Flagyl
Area Under the Curve at Steady State
Area under the curve at steady state (AUCss)
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
Loading Dose Maximum Concentration
Loading Dose Maximum concentration (Cmax)
Time frame: 2-5 days of study drug administration
Loading Dose Minimum Concentration
Loading Dose Minimum Concentration (mg/L)
Time frame: 2-5 days of study drug administration
Multiple Dose Maximum Concentration
Multiple Dose Maximum Concentration (mg/L)
Time frame: 2-5 days of study drug administration
Multiple Dose Minimum Concentration
Multiple Dose Minimum Concentration (mg/L)
Time frame: 2-5 days of study drug administration
Clearance
Clearance (L/h/kg)
Time frame: 2-5 days of study drug administration
Volume of Distribution
Volume of Distribution (L/kg)
Time frame: 2-5 days of study drug administration
| Milestone | Metronidazole IV |
|---|---|
| Started | 24 |
| Completed | 24 |
| Not completed | 0 |
Area under the curve at steady state (AUCss)
| mg*hr/L | Metronidazole IV |
|---|---|
| Area Under the Curve at Steady State | 178.0 (66.0 to 472.0) |
Loading Dose Maximum concentration (Cmax)
| mg/L | Metronidazole IV |
|---|---|
| Loading Dose Maximum Concentration | 16.54 (9.18 to 19.63) |
Loading Dose Minimum Concentration (mg/L)
| mg/L | Metronidazole IV |
|---|---|
| Loading Dose Minimum Concentration | 9.20 (3.21 to 12.82) |
Multiple Dose Maximum Concentration (mg/L)
| mg/L | Metronidazole IV |
|---|---|
| Multiple Dose Maximum Concentration | 16.51 (8.71 to 34.05) |
Multiple Dose Minimum Concentration (mg/L)
| mg/L | Metronidazole IV |
|---|---|
| Multiple Dose Minimum Concentration | 11.62 (1.29 to 27.05) |
Clearance (L/h/kg)
| L/h/kg | Metronidazole IV |
|---|---|
| Clearance | 0.043 (0.016 to 0.105) |
Volume of Distribution (L/kg)
| L/kg | Metronidazole IV |
|---|---|
| Volume of Distribution | 0.99 (0.38 to 2.67) |
Collected over From first dose through 10 days post dose.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Treatment | — | 5/24 (20.8%) | 17/24 (70.8%) |
| Event | Treatment |
|---|---|
| Necrotising colitisGastrointestinal disorders | 2/24 |
| DeathGeneral disorders | 1/24 |
| Cardiac arrestCardiac disorders | 1/24 |
| Patent ductus arteriosus repairSurgical and medical procedures | 1/24 |
| Septic shockInfections and infestations | 1/24 |
| Renal failure acuteRenal and urinary disorders | 1/24 |
| Event | Treatment |
|---|---|
| Other non-serious, infrequent adverse eventsGeneral disorders | 7/24 |
| Endocrine disorders Adrenal InsufficiencyEndocrine disorders | 4/24 |
| ConvulsionNervous system disorders | 3/24 |
| Dermatitis diaperSkin and subcutaneous tissue disorders | 3/24 |
| Age, Continuous(days) | Treatment |
|---|---|
| Median | 27 (1 to 82) |
| Age, Continuous(weeks) | Treatment |
|---|---|
| Mean | 25 (23 to 31) |
| Sex: Female, Male(Participants) | Treatment |
|---|---|
| Female | 16 |
| Male | 8 |
| Ethnicity (NIH/OMB)(Participants) | Treatment |
|---|---|
| Hispanic or Latino | 6 |
| Not Hispanic or Latino | 18 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Treatment |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 1 |
| Black or African American | 7 |
| White | 16 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(participants) | Treatment |
|---|---|
| United States | 24 |
| Birth Weight(grams) | Treatment |
|---|---|
| Median | 740 (431 to 1466) |
This study is completed, as verified in Jan 2014. You cannot join it, but the record below documents what was studied.
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Michael Cohen-Wolkowiez