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

NCT04867993 | Unknown

• 1 other identifier: 0901-2-864/18
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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. 1.Retrospective evaluation of amikacin therapeutic drug monitoring (TDM) in asphyxiated neonates treated with hypothermia (University hospital Leuven, VUmc Amsterdam)
2. 2.Development of population PK model derived amikacin dosing recommendation
3. 3.Prospective PK study with validation of the new dosing regimen (UCC Sarajevo, UCC Tuzla)

Conditions

Asphyxia Neonatorum

Keywords

Amikacin; Pharmacokinetics; Hypothermia; Newborn

Outcome Measures

Primary Outcomes (7)

• Maximum Plasma Concentration [Cmax]

  the first plasma concentration measured after the dosing

  5 years

• Minimum Plasma concentration (Ctrough)

  the last plasma concentration measured after the dosing

  5 years

• 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

• Clearance (CL)

  Clearance of the drug, seen from the last part of the concentration-time curve

  5 years

• Volume of distribution (Vd)

  Volume of distribution of the drug, seen from the early part of the concentration-time curve

  5 years

• Minumum inhibitory concentration (MIC 90)

  concentration of the drug needed to inhibit the growth of 90% of isolates

  5 years

• Creatinine clearance

  clearance of the creatinine calculated by different formulas

  5 years

Secondary Outcomes (1)

• adverse effects of hypothermia

  5 years

Study Arms (2)

asphyxiated neonates treated with amikacin and hypothermia

ACTIVE COMPARATOR

Amikacin (Likacin®; 500 mg/2mL vial; Lisapharma S.p.A., Erba, Italy) is given to the neonate, as an IV infusion via umbilical vein over 20 min by use of a syringe-pump (Braun; B. Braun Medical Inc., Bethlehem, PA USA). Infusion is followed by slow 0.5 mL Sodium chloride 0.9% flush.

Drug: Amikacin

asphyxiated neonates treated with amikacin

PLACEBO COMPARATOR

Amikacin (Likacin®; 500m g/2mL vial; Lisapharma S.p.A., Erba, Italy) is given to the neonate, as an IV infusion via umbilical vein over 20 min by use of a syringe-pump (Braun; B. Braun Medical Inc., Bethlehem, PA USA). Infusion is followed by slow 0.5 mL Sodium chloride 0.9% flush.

Drug: Amikacin

Interventions

Amikacin DRUG

15 mg/kg/36h

asphyxiated neonates treated with amikacin; asphyxiated neonates treated with amikacin and hypothermia

Eligibility Criteria

• Age: Up to 1 Day
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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
• 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)
• 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

You may not qualify if:

• parental informed consent withdrawal
• the occurrence of clinical reasons to stop blood sampling

Sponsors & Collaborators

• University of Sarajevo: lead
• KU Leuven: collaborator
• Amsterdam UMC, location VUmc: collaborator
• Leiden University Medical Center: collaborator
• University Clinical Center Tuzla: collaborator

Study Sites (1)

Pediatric Clinic, University Clinical Centre Sarajevo

Sarajevo, 71000, Bosnia and Herzegovina

RECRUITING

Related Publications (2)

• 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.

  PMID: 22229883 BACKGROUND

• 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.

  PMID: 26248375 BACKGROUND

Related Links

• Related Info
• Related Info

MeSH Terms

Conditions

Asphyxia Neonatorum; Hypothermia

Interventions

Amikacin

Condition Hierarchy (Ancestors)

Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Kanamycin; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Karel Allegaert, MD PhD

  Catholic University Leuven, Belgium

  STUDY CHAIR

Central Study Contacts

Sabina Terzic, MD PhD

CONTACT

+38761207051; sterzic1974@gmail.com

Aida Kulo Cesic, MD PhD

CONTACT

+38761566169; aida.kulo@mf.unsa.ba

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD, Assistant professor

Study Record Dates

• First Submitted: February 24, 2021
• First Posted: April 30, 2021
• Study Start: August 28, 2018
• Primary Completion: August 1, 2022
• Study Completion: December 1, 2022
• Last Updated: April 30, 2021

Record last verified: 2021-04

Locations

BO (1)