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| ID | Type | Description | Link |
|---|---|---|---|
| HHSN27500003I | Other Grant/Funding Number | NICHD |
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| Name | Class |
|---|---|
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
| The Emmes Company, LLC | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment | Experimental | Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael Cohen-wolkowiez, MD | Duke University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHOC Children's | Orange | California | 92868 | United States | ||
| Wesely Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23587979 | Result | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Metronidazole IV | Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment | Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Post Natal Age (Days) |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Curve at Steady State | Area under the curve at steady state (AUCss) | The PK analysis was conducted using samples from 23 subjects. One subject died soon after the loading dose and was excluded from the analysis. Two subjects had no multiple dose samples. Thus data from 20 subjects were used to estimate this PK parameter. | Posted | Median | Full Range | mg*hr/L | 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 |
|
|
From first dose through 10 days post dose.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment | Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Death | General disorders | MedDra | Systematic Assessment | Not related to study drug |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Endocrine disorders Adrenal Insufficiency | Endocrine disorders | MedDra | Systematic Assessment | Not related to study drug |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Michael Cohen-Wolkowiez, MD | Duke Clinical Research Institute | 919668-8812 | michael.cohenwolkowiez@dm.duke.edu |
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| ID | Term |
|---|---|
| D020345 | Enterocolitis, Necrotizing |
| D047928 | Premature Birth |
| D018805 | Sepsis |
| ID | Term |
|---|---|
| D004760 | Enterocolitis |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D008795 | Metronidazole |
| ID | Term |
|---|---|
| D009593 | Nitroimidazoles |
| D009574 | Nitro Compounds |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
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|
| Wichita |
| Kansas |
| 67214 |
| United States |
| Duke University | Durham | North Carolina | 27715 | United States |
| Full Range |
| days |
|
| Age, Continuous | Gestational age (weeks) | Mean | Full Range | weeks |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Birth Weight | Median | Full Range | grams |
|
| Participants |
|
|
| Primary | Loading Dose Maximum Concentration | Loading Dose Maximum concentration (Cmax) | The sample size contains the number of subjects that had the sample of interest collected. | Posted | Median | Full Range | mg/L | 2-5 days of study drug administration |
|
|
|
| Primary | Loading Dose Minimum Concentration | Loading Dose Minimum Concentration (mg/L) | The sample size contains the number of subjects that had the sample of interest collected. | Posted | Median | Full Range | mg/L | 2-5 days of study drug administration |
|
|
|
| Primary | Multiple Dose Maximum Concentration | Multiple Dose Maximum Concentration (mg/L) | The PK analysis was conducted using samples from 23 subjects. One subject died soon after the loading dose and was excluded from the analysis. Two subjects had no multiple dose samples. Thus data from 20 subjects were used to estimate the multiple dose PK parameter. | Posted | Median | Full Range | mg/L | 2-5 days of study drug administration |
|
|
|
| Primary | Multiple Dose Minimum Concentration | Multiple Dose Minimum Concentration (mg/L) | The sample size contains the number of subjects that had the sample of interest collected. | Posted | Median | Full Range | mg/L | 2-5 days of study drug administration |
|
|
|
| Primary | Clearance | Clearance (L/h/kg) | The PK analysis was conducted using samples from 23 subjects. One subject died soon after the loading dose and was excluded from the analysis. Two subjects had no multiple dose samples. Thus data from 20 subjects were used to estimate the PK parameter. | Posted | Median | Full Range | L/h/kg | 2-5 days of study drug administration |
|
|
|
| Primary | Volume of Distribution | Volume of Distribution (L/kg) | The PK analysis was conducted using samples from 23 subjects. One subject died soon after the loading dose and was excluded from the analysis. Two subjects had no multiple dose samples. Thus data from 20 subjects were used to estimate the PK parameter. | Posted | Median | Full Range | L/kg | 2-5 days of study drug administration |
|
|
|
| 5 |
| 24 |
| 17 |
| 24 |
| Cardiac arrest | Cardiac disorders | MedDra | Systematic Assessment | Not related to study drug |
|
| Necrotising colitis | Gastrointestinal disorders | MedDra | Systematic Assessment | Not related to study drug |
|
| Patent ductus arteriosus repair | Surgical and medical procedures | MedDra | Systematic Assessment | Not related to study drug |
|
| Septic shock | Infections and infestations | MedDra | Systematic Assessment | Not related to study drug |
|
| Renal failure acute | Renal and urinary disorders | MedDra | Systematic Assessment | Not related to study drug |
|
|
| Convulsion | Nervous system disorders | MedDra | Systematic Assessment | Not related to study drug |
|
| Dermatitis diaper | Skin and subcutaneous tissue disorders | MedDra | Systematic Assessment | Not related to study drug |
|
| Other non-serious, infrequent adverse events | General disorders | MedDra | Systematic Assessment | Not related to study drug |
|
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| D007410 |
| Intestinal Diseases |
| D007752 | Obstetric Labor, Premature |
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001393 |
| Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |