Asphyxia Neonatorum Clinical Trial
— AmicoolOfficial title:
Amikacin Pharmacokinetics to Optimize Dosing Recommendations and Patho(Physiological) Considerations in Neonates With Perinatal Asphyxia Treated With Hypothermia
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)
Status | Recruiting |
Enrollment | 80 |
Est. completion date | December 2022 |
Est. primary completion date | August 2022 |
Accepts healthy volunteers | No |
Gender | All |
Age group | N/A to 1 Day |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
Bosnia and Herzegovina | Pediatric Clinic, University Clinical Centre Sarajevo | Sarajevo |
Lead Sponsor | Collaborator |
---|---|
University of Sarajevo | KU Leuven, Leiden University Medical Center, University Clinical Center Tuzla, VU University Medical Center |
Bosnia and Herzegovina,
De Cock RF, Allegaert K, Schreuder MF, Sherwin CM, de Hoog M, van den Anker JN, Danhof M, Knibbe CA. Maturation of the glomerular filtration rate in neonates, as reflected by amikacin clearance. Clin Pharmacokinet. 2012 Feb 1;51(2):105-17. doi: 10.2165/11595640-000000000-00000. — View Citation
Smits A, De Cock RF, Allegaert K, Vanhaesebrouck S, Danhof M, Knibbe CA. Prospective Evaluation of a Model-Based Dosing Regimen for Amikacin in Preterm and Term Neonates in Clinical Practice. Antimicrob Agents Chemother. 2015 Oct;59(10):6344-51. doi: 10.1128/AAC.01157-15. Epub 2015 Jul 27. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Maximum Plasma Concentration [Cmax] | the first plasma concentration measured after the dosing | 5 years | |
Primary | Minimum Plasma concentration (Ctrough) | the last plasma concentration measured after the dosing | 5 years | |
Primary | Area under the plasma concentration versus time curve (AUC) | Area under the plasma concentration versus time curve calculated based on a trapezoidal rule | 5 years | |
Primary | Clearance (CL) | Clearance of the drug, seen from the last part of the concentration-time curve | 5 years | |
Primary | Volume of distribution (Vd) | Volume of distribution of the drug, seen from the early part of the concentration-time curve | 5 years | |
Primary | Minumum inhibitory concentration (MIC 90) | concentration of the drug needed to inhibit the growth of 90% of isolates | 5 years | |
Primary | Creatinine clearance | clearance of the creatinine calculated by different formulas | 5 years | |
Secondary | adverse effects of hypothermia | adverse outcomes of hypothermia | 5 years |
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