NeoFent-I Study; Fentanyl Treatment in Newborn Infants; a Pharmacokinetic, Pharmacodynamic and Pharmacogenetic Study

Study Overview
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Brief Summary
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The study will assess the efficacy of fentanyl using a pharmacokinetic/pharmacodynamic (PK/PD) model where the concentration of the drug is related to effect curve (pain score change in response to standardized procedural pain). Further cortical, physiological and biochemical responses to fentanyl will be assessed, elucidating the feasibility before the main study project (NeoOpioid) start.

Official Title
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NeoFent-I Study; Fentanyl Treatment in Newborn Infants; a Pharmacokinetic, Pharmacodynamic and Pharmacogenetic Study. Prestudy to NeoOpioid; No Pain During Infancy by Adapting Off-patent Medicines. EU FP7:HEALTH - 2007-4.2-1

Conditions
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Pain

Intervention / Treatment
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* Drug: Fentanyl (5 microgram/ml) prediluted ampoules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical indication for analgesia before any of following procedures; insertion of peripheral IV-catheter insertion of arterial cannula insertion of chest tube other skin breaking procedure. Possibility to obtain blood samle after the procedure (indwelling line) Infants all gestational ages. Postnatal age 0-28 days Informed written parental concent Exclusion Criteria: Concurrent or previous opioid administration (72 h interval required) Abdominal surgery Major chromosomal anomaly Neonatal encephalopathy Use of muscle relaxant Hypothermia treatment after hypoxic-ischemic insult Clinical or biochemical evidence of hepatic failure Participation in other intervention trial

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 28 Days

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fentanyl for procedural pain<br>A dose of Fentanyl 5 microgram/ml, 0.5 microgram/kg (anticipated medium pain) or 2 microgram/kg (anticipated strong pain) will be given prior to a painful procedure during NICU-care. Repeated doses or complementary analgesics will be administered according to pain assessment and clinical judgement. This is not an RCT with several arms. | Drug: Fentanyl (5 microgram/ml) prediluted ampoules<br>* Bolus; Fentanyl (5 microgram/ml) 0,5 microgram/kg (0.1 ml/kg) is administered over 1 min starting 3-5 min before the lighter skin breaking procedure. Fentanyl (5 microgram/ml) 2 microgram/kg is administered over 10 min before the start of the more painful procedur ( pleura drainage or tracheal intubation).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics; fentanyl clearance | Serum concentration will be analysed and the clearance will be calculated with NONMEM pharmacokinetics. | 48 hours | 
| Pharmacokinetics; fentanyl clearance | The serum concentration values will be analysed as Area under the curve, AUC | 6 hours | 
| Pharmacodynamics; Amplitude integrated electroencephalography (aEEG) | Background activity | 6 hours | 
| Pharmacodynamics; Amplitude integrated electroencephalography (aEEG), | Seizure activity | 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamics, change in vital parameters | Change in heart rate | 6 hours | 
| Pharmacodynamics, change in vital parameters | Change in mean arterial blood pressure | 6 hours | 
| Pharmacodynamics, change in vital parameters | Change in near infrared spectroscopy | 6 hours | 
| Pharmacodynamics, behavioural response | Pain assessment with the Premature Infant Pain Profile-revised (PIPP) score for procedural pain (0-21, with the highest value if strong pain in extremely preterm infants) | 6 hours | 
| Pharmacodynamics, hormonal response | Blood levels of cortisol | 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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analgesia, neonates, procedural pain, pain assessment, physiological response, pharmacogenetics