Clinical trial NCT04867135: Population Pharmacokinetics of Amikacin in Neonates
Official title: Population Pharmacokinetics of Amikacin in Suspected Cases of Neonatal Sepsis: Multicenter Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Neonatal Sepsis, Late-Onset
Keywords: Neonatal Sepsis
Amikacin
Population Pharmacokinetic
Neonate
Lead sponsor: Pontificia Universidad Catolica de Chile
Sponsor class: OTHER
First posted: 2021-04-30
Enrollment: 138
Sex: ALL
Minimum age (years): 3
Maximum age (years): 1
Standard ages: CHILD
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients admitted to neonatal intensive care units of two hospitals of high-complexity in Chile

Brief 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 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.

Eligibility criteria: Inclusion Criteria:

* Receive at least one dose of Amikacin
* Be at least three days old (72 hours)

Exclusion Criteria:

* Receive the first dose of Amikacin in a healthcare center other than those included in the research
* Patient on renal replacement therapy

Primary outcomes:
measure: Volume of Distribution (L/Kg) of Amikacin
timeFrame: first dose amikacin (1 day)
measure: Clearance (L/h) of Amikacin
timeFrame: first dose amikacin (1 day)
measure: PK/PD targets of amikacin
timeFrame: first dose amikacin (1 day)
Secondary outcomes:
Other outcomes:
Locations:
city: Santiago
country: Chile
facility: Hospital Clínico UC-Christus
Study officials:
affiliation: Facultad de Medicina. Pontificia Universidad Católica de Chile
name: Nicolas F Severino, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Sherwin 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.