Clinical Trial on Individual Characteristics Affecting Pain Drug Therapy in Neonates

Study Overview
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Brief Summary
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Children differ from adults with respect to growth and development but also immaturity of various pharmacological mechanisms. Dosing schemes in children are usually derived in an empirical manner from clinical trials in adult patient groups. All this poses neonates to an increased risk for therapeutic failure and adverse drug reactions. Medicinal products studied during this project are among the ones with the highest needs for research in the pediatric intensive care. This project focuses on the necessity to integrate subject's individual characteristics to assist clinical decision-making in drug therapy. The investigators explore the mechanisms defining the dose response in pediatric populations. The results obtained with these studies will help to find safer drug dosing regimens in this delicate patient population.

Official Title
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Individualising Drug Therapy in Neonates Using Pharmacogenomic Profiling, Population Based Modeling and Simulations

Conditions
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Critical Illness

Intervention / Treatment
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* Drug: propofol
* Drug: oxycodone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Given informed consent by the guardian of an eligible patient. Patient is more than 24 weeks old and has a body weight more than 500 g. Patient needs intensive care treatment based on a clinical decision by a neonatologist and receives propofol or oxycodone on their therapy. Attending neonatologist makes the decision to prescribe propofol for scheduled short procedural sedation or oxycodone for analgesia as well as all other treatment related decisions. Exclusion Criteria: Eligible patients guardian declines to give informed consent. A previous history of intolerance to the study drugs or to related compounds and additives. History of any kind of drug allergy. Participation in any other studies concomitantly or within one month prior to the entry into this study.

Ages Eligible for Study
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Minimum Age: 24 Weeks
Maximum Age: 40 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Propofol<br>Plasma samples and patient data are collected prospectively from 40 neonates who receive propofol as part of their care in the neonatal intensive care unit at the Turku University Hospital, Turku, Finland. | Drug: propofol<br> <br> |
| Active Comparator: Oxycodone<br>Plasma samples and patient data are collected prospectively from 40 neonates who receive oxycodone as part of their care in the neonatal intensive care unit at the Turku University Hospital, Turku, Finland. | Drug: oxycodone<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) of propofol and oxycodone. | Primary outcome is to build up a population pharmacometric model to describe pharmacokinetics of propofol and oxycodone based on drug concentrations analyzed from the plasma samples. | 24 hours post-dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of biometric and genomic covariates on AUC | Covariate analysis and simulations to individualize population models | 24 hours post-dose | 
| Efficacy of propofol in procedural anesthesia in neonates | Number of Participants with Adverse Events as a Measure of Safety and Tolerability during procedural anesthesia for intratracheal intubation in neonates | 24 hours | 
| Efficacy of oxycodone as an analgesic in neonates during mechanical ventilation | Number of Participants with Adverse Events as a Measure of Safety and Tolerability in neonates after oxycodone administration during mechanical ventilation. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neonatal intensive care, need for intratracheal intubation