Fentanyl treatment in newborn infants: A Pharmacokinetic, Pharmacodynamic, and Pharmacogenetic Study(PK/PD model)

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 180

Inclusion Criteria

1.Clinical indication (or pain scoring, see 7.2.1: PIPP = 7, or BIIP = 3, or EDIN = 6) for analgesia before any of following procedure:
a.Insertion of peripheral IV-catheter
b.Insertion of arterial cannula
c.Other skin breaking procedure
d.Insertion of chest tube
Other painful/stressful procedure might be considered if indicated by pain scoring used, eg. endotracheal suction.

2.Possibility to obtain blood sample after the procedure (indwelling line or the procedure is insertion of line as clinically indicated)
3.Infants of all gestational ages (preferably preterm born at a gestational age of 24 0/7 to 32 6/7 weeks and term infants at 38-41 gestational weeks (gw) for the first 65 in the PK/PD model)
4.Postnatal age 0-28 days, ie up to an age corresponding to 44 post conceptional weeks.
5.Informed written parental consent.

The infants will be analyzed in five postconceptional age groups and the target number of infants are:
23-26 gwn= 20
27-28 gwn= 30
29-32 gwn= 40
33-36 gw n= 40
37-42 gwn= 50
The same infant can be included for another painful procedure after at least 2 weeks interval, ie when has reached the next gestational age group. In total maximum three series of blood sampling, according to weight.

Are the trial subjects under 18? yes
Number of subjects for this age range: 180
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Concurrent or previous other opioid administration:
a. for morfine a 72 h interval required
b. for remifentanil a 6 h interval required
c. for alfentanil a 24 h interval required
d. (previous fentanyl administration is NOT an exclusion criterion, but baseline concentration needed before study drug administered)
2.Abdominal surgery (since intra-abdominal pressure influences fentanyl metabolism)
3.Major chromosomal anomaly, e.g. trisomy
4.Neonatal encephalopathy (e.g. seizures, lethargy/coma)
5.Use of muscular relaxant
6.Hypothermia treatment after hypoxic-ischemic insult
7.Clinical or biochemical evidence of hepatic failure (e.g. cholestasis, hepatic coagulopathy, hypoalbuminaemia) or renal failure (serum creatinine > 132 micro mol/L corresponding to >1.5 mg/dL42)
8.Participation in other clinical intervention trial (including blood sampling procedures other than clinical routine, and administration of other investigational medicinal product) within 72 hours before study start and throughout the study

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 1. A first PK/PD study will assess the efficacy of fentanyl using a PK/PD model where log concentration of the drug is related to pain score change in response to standardised procedural pain. This will be a feasibility study for the main clinical efficacy and safety NeoOpioid study that will implement the optimal fentanyl dosage derived from this model and will aim at further explaining the impact of dependent and confounding factors on the dosage needed (i.e. immaturity, birth weight, morbidity, physiologic stress responses, hemodynamics, and genetic variability).;Secondary Objective: Evaluate cortical and hormonal responses to pain management with fentanyl.;Primary end point(s): To assess the fentanyl total body clearance (dose related to concentration AUC) and <br>derive an algorithm for fentanyl administration from the PK/PD model to be used in the efficacy/safety clinical study (NeoOpioid). <br>;Timepoint(s) of evaluation of this end point: 0, 10 min 2 h, 4h, 8 h and 24 h

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): To investigate cortical hemodynamic responses (NIRS) in relation to neurophysiological<br>and behavioural responses and blood levels of stress hormones.

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