Population Pharmacokinetics of Amikacin in Neonates

Completed

• Conditions: Neonatal Sepsis, Late-Onset
• Interventions: Drug: Amikacin Sulfate Injection

• Registration Number: NCT04867135
• Lead Sponsor: Pontificia Universidad Catolica de 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.

Study Timeline

• Study Start: 2019-12-01
• Status Verified: 2021-04
• Study First Submitted: 2021-04-27
• Study First Submitted QC: 2021-04-27
• Study First Posted: 2021-04-30
• Primary Completion: 2021-07-31
• Study Completion: 2021-09-03
• Last Update Submitted: 2022-03-29
• Last Update Posted: 2022-04-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 138

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
No Sepsis / Sepsis	Amikacin Sulfate Injection	To compare amikacin PK / PD models of newborns with a confirmed diagnosis of sepsis (clinical or microbiological) and with ruled out sepsis.

Primary Outcome Measures

Name	Time	Method
PK/PD targets of amikacin	first dose amikacin (1 day)	Peak Plasma Concentration (Cmax) over 8 fold Minimum Inhibitory Concentration (MIC) or Cmax: 24-35 mg/L
Volume of Distribution (L/Kg) of Amikacin	first dose amikacin (1 day)	The mean population parameter and their interindividual variability in neonates with suspected sepsis
Clearance (L/h) of Amikacin	first dose amikacin (1 day)	The mean population parameter and their interindividual variability in neonates with suspected sepsis

Trial Locations

Locations (1)

Hospital Clínico UC-Christus; 🇨🇱 Santiago, Chile