Serious Systemic InfectionsPhase 1PTN_METRONCT01222585
Metronidazole Pharmacokinetics (PK) in Premature Infants
A Phase 1 study testing Metronidazole in people with Serious Systemic Infections and Necrotizing Enterocolitis, run by Michael Cohen-Wolkowiez at 3 sites in United States.
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. Read more about this study
- Who is it for?
- Ages Up to 90 days
- Conditions the study is for
- Serious Systemic Infections, Necrotizing Enterocolitis
- What is being tested?
- Metronidazole
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 3 sitesUnited States
- Study dates
- Jan 2011to Nov 2011
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 90 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Duke University
Durham, North Carolina, 27715
CHOC Children's
Orange, California, 92868
Wesely Medical Center
Wichita, Kansas, 67214
About this study
Official title: Safety and Pharmacokinetics of Multiple Dose Metronidazole in Premature Infants
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.
- Being tested
- Metronidazole
- Keywords
- Metronidazole, Neonate, Premature, Sepsis, Necrotizing enterocolitis
- Medical subject headings
- Enterocolitis, Necrotizing, Premature Birth, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetronidazoleDrug
Also called Flagyl
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.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours Receives: Drug: Metronidazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Curve at Steady State
Area under the curve at steady state (AUCss)
Measured: 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)
Measured: 2-5 days of study drug administration
Loading Dose Minimum Concentration
Loading Dose Minimum Concentration (mg/L)
Measured: 2-5 days of study drug administration
Multiple Dose Maximum Concentration
Multiple Dose Maximum Concentration (mg/L)
Measured: 2-5 days of study drug administration
Multiple Dose Minimum Concentration
Multiple Dose Minimum Concentration (mg/L)
Measured: 2-5 days of study drug administration
Clearance
Clearance (L/h/kg)
Measured: 2-5 days of study drug administration
Volume of Distribution
Volume of Distribution (L/kg)
Measured: 2-5 days of study drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2010 (estimated)
- Study startJan 2011
- Primary completionNov 2011
- Study completionNov 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Serious Systemic InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michael Cohen-Wolkowiez
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), The Emmes Company, LLC
- Responsible party
- Sponsor-investigator, Michael Cohen-Wolkowiez, Duke University
- Investigators
- Michael Cohen-wolkowiez, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01222585
- Sponsor's protocol ID
- Pro00024571
- Other IDs
- HHSN27500003I
- Acronym
- PTN_METRO
- Status last verified
- Jan 2014
- First submitted
- 6 Oct 2010
- Last updated
- 6 Feb 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 23587979
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Pharmacokinetics of Multiple Dose Metronidazole in Premature Infants
- ClinicalTrials.gov ID
- NCT01222585
- Acronym / sponsor ID
- PTN_METRO / Pro00024571
- Keywords
- Metronidazole, Neonate, Premature, Sepsis, Necrotizing enterocolitis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Michael Cohen-WolkowiezUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), The Emmes Company, LLC
- Study start
- Jan 2011
- Primary completion
- Nov 2011 (actual)
- Study completion
- Nov 2011 (actual)
- First posted
- 18 Oct 2010 (estimated)
- Results
- Posted 18 Dec 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: MetronidazoleIntravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours |
Who may qualify
- Ages
- Up to 90 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetronidazoleAlso: FlagylMetronidazole 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. | Drug | Treatment |
Primary outcome
Area Under the Curve at Steady State
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
Area under the curve at steady state (AUCss)
Loading Dose Maximum Concentration
Time frame: 2-5 days of study drug administration
Loading Dose Maximum concentration (Cmax)
Loading Dose Minimum Concentration
Time frame: 2-5 days of study drug administration
Loading Dose Minimum Concentration (mg/L)
Multiple Dose Maximum Concentration
Time frame: 2-5 days of study drug administration
Multiple Dose Maximum Concentration (mg/L)
Multiple Dose Minimum Concentration
Time frame: 2-5 days of study drug administration
Multiple Dose Minimum Concentration (mg/L)
Clearance
Time frame: 2-5 days of study drug administration
Clearance (L/h/kg)
Volume of Distribution
Time frame: 2-5 days of study drug administration
Volume of Distribution (L/kg)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23587979Cohen-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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Cohen-wolkowiez, MD principal investigator
Duke University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Metronidazole in people with Serious Systemic Infections and Necrotizing Enterocolitis, run by Michael Cohen-Wolkowiez at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Dec 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Curve at Steady State (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). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01222585, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2014.