Neonatal Sepsis, Late-OnsetNCT04867135
Population Pharmacokinetics of Amikacin in Neonates
An observational study of Neonatal Sepsis, Late-Onset, run by Pontificia Universidad Catolica de Chile at 1 site in Chile.
Trial summary
Aminoglycosides such as Amikacin are routinely used in newborns for the treatment of neonatal sepsis due to gram-negative bacilli. Despite the frequency of this indication, it has not yet been possible to establish definitive dosage schedules that ensure effectiveness and low risk of toxicity, due to the high… Read more about this study
- Who is it for?
- Ages 3 days to 1 month
- Conditions the study is for
- Neonatal Sepsis, Late-Onset
- What is being tested?
- Amikacin Sulfate Injection
- Type of treatment
- Injection or infusion
- How many people
- 138 participants
- Where
- 1 siteChile
- Study dates
- 1 Dec 2019to 3 Sep 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
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 3 days to 1 month
- All sexes
- Child
Study population: Patients admitted to neonatal intensive care units of two hospitals of high-complexity in Chile
Who may be able to join
- Receive at least one dose of Amikacin
- Be at least three days old (72 hours)
Who cannot join
- Receive the first dose of Amikacin in a healthcare center other than those included in the research
- Patient on renal replacement therapy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Population Pharmacokinetics of Amikacin in Suspected Cases of Neonatal Sepsis: Multicenter Study
Aminoglycosides such as Amikacin are routinely used in newborns for the treatment of neonatal sepsis due to gram-negative bacilli. Despite the frequency of this indication, it has not yet been possible to establish definitive dosage schedules that ensure effectiveness and low risk of toxicity, due to the high pharmacokinetic variability observed in this population.
In addition to anthropometric variables, evidence from retrospective studies suggests that sepsis could be capable of significantly modifying the pharmacokinetics of aminoglycosides in neonates, but the investigators suggest conducting prospective studies of higher methodological quality to verify this hypothesis.
Due to the lack of pharmacokinetic and pharmacodynamic (PK / PD) studies of Amikacin in this group of patients, the investigators have raised the need to develop a prospective observational study; describing a PK / PD model of amikacin in newborns with suspected sepsis.
Read the detailed description
Three blood samples will be taken from each of the 138 participants. As a standard of care, a sample will always be taken at 0.5h (Cmax) after the first dose and a sample before the second dose, which can be at 24h, 36h, or 48h as per physician indication. The third sample will be collected according to what has been assigned by a block randomization method, in one of the following moments: 1, 2, 4, 8, 12 or 18 hours after the administration of the first dose of Amikacin.
The methods used to analyze the samples will be: Particle Enhanced Turbidimetric Immunoassay (PETIA), Architect C8000; and Homogeneous Microparticle Immunoassay in Solution (KIMS), Roche systems. The determination of the susceptibility and minimum Inhibitory Concentration (MIC) will be carried out by the laboratories of each hospital by agar dilution method.
PK/PD profile of amikacin will be evaluated with NONMEM (non-linear mixed effects modelling) software for the analysis.
- Conditions
- Neonatal Sepsis, Late-Onset
- Being tested
- Amikacin Sulfate Injection
- Keywords
- Neonatal Sepsis, Amikacin, Population Pharmacokinetic, Neonate
- Medical subject headings
- Neonatal Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Amikacin Sulfate InjectionDrug
Also called Amikacin
The dose and frequency of amikacin was defined by each hospital.
| Study group | Role | What they receive |
|---|---|---|
| No Sepsis / Sepsis | To compare amikacin PK / PD models of newborns with a confirmed diagnosis of sepsis (clinical or microbiological) and with ruled out sepsis. Receives: Drug: Amikacin Sulfate Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Volume of Distribution (L/Kg) of Amikacin
The mean population parameter and their interindividual variability in neonates with suspected sepsis
Measured: first dose amikacin (1 day)
Clearance (L/h) of Amikacin
The mean population parameter and their interindividual variability in neonates with suspected sepsis
Measured: first dose amikacin (1 day)
PK/PD targets of amikacin
Peak Plasma Concentration (Cmax) over 8 fold Minimum Inhibitory Concentration (MIC) or Cmax: 24-35 mg/L
Measured: first dose amikacin (1 day)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2021
- Study start1 Dec 2019
- Primary completion31 Jul 2021
- Study completion3 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Neonatal Sepsis, Late-OnsetStudies of the same condition, open and under way.
- More trials run by Pontificia Universidad Catolica de ChileThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 138 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pontificia Universidad Catolica de Chile
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nicolas F Severino, PharmD, Principal investigator, Facultad de Medicina. Pontificia Universidad Católica de Chile
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04867135
- Sponsor's protocol ID
- 190325002
- Status last verified
- Apr 2021
- First submitted
- 27 Apr 2021
- Last updated
- 7 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lingvall M, Reith D, Broadbent R. The effect of sepsis upon gentamicin pharmacokinetics in neonates. Br J Clin Pharmacol. 2005 Jan;59(1):54-61. doi: 10.1111/j.1365-2125.2005.02260.x.
PubMed 15606440Sherwin CM, Svahn S, Van der Linden A, Broadbent RS, Medlicott NJ, Reith DM. Individualised dosing of amikacin in neonates: a pharmacokinetic/pharmacodynamic analysis. Eur J Clin Pharmacol. 2009 Jul;65(7):705-13. doi: 10.1007/s00228-009-0637-4. Epub 2009 Mar 21.
PubMed 19305985
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Population Pharmacokinetics of Amikacin in Suspected Cases of Neonatal Sepsis: Multicenter Study
- ClinicalTrials.gov ID
- NCT04867135
- Acronym / sponsor ID
- 190325002
- Conditions
- Neonatal Sepsis, Late-Onset
- Keywords
- Neonatal Sepsis, Amikacin, Population Pharmacokinetic, Neonate
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 138 participants (actual)
- Lead sponsor
- Pontificia Universidad Catolica de ChileUniversity, hospital or other
- Study start
- 1 Dec 2019 (actual)
- Primary completion
- 31 Jul 2021 (actual)
- Study completion
- 3 Sep 2021 (actual)
- First posted
- 30 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Aminoglycosides such as Amikacin are routinely used in newborns for the treatment of neonatal sepsis due to gram-negative bacilli. Despite the frequency of this indication, it has not yet been possible to establish definitive dosage schedules that ensure effectiveness and low risk of toxicity, due to the high pharmacokinetic variability observed in this population.
In addition to anthropometric variables, evidence from retrospective studies suggests that sepsis could be capable of significantly modifying the pharmacokinetics of aminoglycosides in neonates, but the investigators suggest conducting prospective studies of higher methodological quality to verify this hypothesis.
Due to the lack of pharmacokinetic and pharmacodynamic (PK / PD) studies of Amikacin in this group of patients, the investigators have raised the need to develop a prospective observational study; describing a PK / PD model of amikacin in newborns with suspected sepsis.
Detailed description
Three blood samples will be taken from each of the 138 participants. As a standard of care, a sample will always be taken at 0.5h (Cmax) after the first dose and a sample before the second dose, which can be at 24h, 36h, or 48h as per physician indication. The third sample will be collected according to what has been assigned by a block randomization method, in one of the following moments: 1, 2, 4, 8, 12 or 18 hours after the administration of the first dose of Amikacin.
The methods used to analyze the samples will be: Particle Enhanced Turbidimetric Immunoassay (PETIA), Architect C8000; and Homogeneous Microparticle Immunoassay in Solution (KIMS), Roche systems. The determination of the susceptibility and minimum Inhibitory Concentration (MIC) will be carried out by the laboratories of each hospital by agar dilution method.
PK/PD profile of amikacin will be evaluated with NONMEM (non-linear mixed effects modelling) software for the analysis.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| No Sepsis / Sepsis | – | Drug: Amikacin Sulfate InjectionTo compare amikacin PK / PD models of newborns with a confirmed diagnosis of sepsis (clinical or microbiological) and with ruled out sepsis. |
Who may qualify
- Ages
- 3 days to 1 month
- Sex
- All
- Age groups
- Child
- Study population
- Patients admitted to neonatal intensive care units of two hospitals of high-complexity in Chile
Key inclusion criteria (2 listed)
- Receive at least one dose of Amikacin
- Be at least three days old (72 hours)
Key exclusion criteria (2 listed)
- Receive the first dose of Amikacin in a healthcare center other than those included in the research
- Patient on renal replacement therapy
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 |
|---|---|---|
| Amikacin Sulfate InjectionAlso: AmikacinThe dose and frequency of amikacin was defined by each hospital. | Drug | No Sepsis / Sepsis |
Primary outcome
Volume of Distribution (L/Kg) of Amikacin
Time frame: first dose amikacin (1 day)
The mean population parameter and their interindividual variability in neonates with suspected sepsis
Clearance (L/h) of Amikacin
Time frame: first dose amikacin (1 day)
The mean population parameter and their interindividual variability in neonates with suspected sepsis
PK/PD targets of amikacin
Time frame: first dose amikacin (1 day)
Peak Plasma Concentration (Cmax) over 8 fold Minimum Inhibitory Concentration (MIC) or Cmax: 24-35 mg/L
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2022.
- Background: PubMed 15606440Lingvall M, Reith D, Broadbent R. The effect of sepsis upon gentamicin pharmacokinetics in neonates. Br J Clin Pharmacol. 2005 Jan;59(1):54-61. doi: 10.1111/j.1365-2125.2005.02260.x.
- Background: PubMed 19305985Sherwin CM, Svahn S, Van der Linden A, Broadbent RS, Medlicott NJ, Reith DM. Individualised dosing of amikacin in neonates: a pharmacokinetic/pharmacodynamic analysis. Eur J Clin Pharmacol. 2009 Jul;65(7):705-13. doi: 10.1007/s00228-009-0637-4. Epub 2009 Mar 21.
- Individual participant dataSharing planned: No
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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.
Nicolas F Severino, PharmD principal investigator
Facultad de Medicina. Pontificia Universidad Católica de Chile
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Neonatal Sepsis, Late-Onset, run by Pontificia Universidad Catolica de Chile at 1 site in Chile.
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 2 inclusion and 2 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 7 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Chile. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Volume of Distribution (L/Kg) of Amikacin (time frame: first dose amikacin (1 day)). The study lists 3 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 NCT04867135, which also lists 2 linked publications.
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 7 Apr 2022.