Amikacin Pharmacokinetics to Optimize Dosing Recommendations in Neonates With Perinatal Asphyxia Treated With Hypothermia

• Status: Recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

Summary

As a part of a project on perinatal clinical pharmacology, the primary aim of the present project is to study amikacin pharmacokinetics (PK) and physiology in asphyxiated neonates treated with therapeutic hypothermia and to provide amikacin dosing recommendations, which will be validated prospectively. For this purpose, we aim to first collect retrospective data on amikacin available in neonates treated with hypothermia in the neonatal intensive care unit (NICU)s in Leuven and Amsterdam, and consequently to propose the dosing regimen to be used in the prospective amikacin PK study at our NICU in University Clinical Center (UCC) Sarajevo. At our NICU we aim to collect amikacin PK observations and other covariates in at least 40 neonates while treated with hypothermia and after re-warming period (a paired analysis), and in asphyxiated neonates not treated with hypothermia (control group).

We hereby will use a stepwise approach, as initially used to develop and to validate an amikacin dosing regimen in preterm and term neonates (De Cock RFW et al., 2012, Smits A et al, 2015).

A 3-step approach will be used, of which different parts will be conducted in different contributing hospitals:

1. Retrospective evaluation of amikacin therapeutic drug monitoring (TDM) in asphyxiated neonates treated with hypothermia (University hospital Leuven, VUmc Amsterdam)

2. Development of population PK model derived amikacin dosing recommendation

3. Prospective PK study with validation of the new dosing regimen (UCC Sarajevo, UCC Tuzla)

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Sarajevo
• Collaborators: KU Leuven; Leiden University Medical Center; University Clinical Center Tuzla; VU University Medical Center
• Treatments: Amikacin

Criteria

Inclusion Criteria:

Inclusion criteria for hypothermia group (University Clinical Centre Sarajevo)

• signed parental informed written consent

• newborn with GA ≥36 weeks

• newborn to whom amikacin is administered by intravenous route for clinical indications

• newborn with perinatal asphyxia treated with hypothermia

Inclusion criteria for control group (University Clinical Centre Tuzla)

• signed parental informed written consent

• newborn to whom amikacin is administered by intravenous route for clinical indications

• newborn with GA ≥36 weeks

• newborn with perinatal asphyxia defined following Bristol hypothermia protocol from 2015

• Apgar score of ≤5 at 10 minutes after birth OR

• Continued need for resuscitation, including endotracheal or mask ventilation, at 10 min after birth OR

• Acidosis defined as either umbilical cord pH or any arterial, venous or capillary pH within 60 min of birth pH<7.00 OR

• Base deficit ≥-16 mmol/L in umbilical cord blood sample or any blood sample within 60 minutes of birth (arterial or venous blood)

Non-inclusion criteria for both groups

• no parental informed consent

• the presence of congenital hepatic or renal pathology

• no central venous or arterial line in situ for non-invasive blood sampling procedures

Exclusion criteria for both groups

• parental informed consent withdrawal

• the occurrence of clinical reasons to stop blood sampling