Clinical trial NCT05805241: Pharmacogenetics Analysis of Fentanyl Administered in Newborns
Official title: Pharmacogenetics Analysis in Newborn Patients on Mechanical Ventilation and Fentanyl Administration
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Fentanyl
Newborn
Pharmacogenetics
Keywords: Fentanyl
Newborn
Pharmacogenetics
Lead sponsor: IRCCS Burlo Garofolo
Sponsor class: OTHER
First posted: 2023-04-07
Enrollment: 66
Sex: ALL
Minimum age (years): 1
Maximum age (years): 28
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All newborns admitted in NICU and mechanically ventilated (MV) who received fentanyl administration for procedural pain.

Brief summary: Fentanyl is an opioid drug used as analgesic and anaesthetic also in Neonatal Intensive Care Units (NICU), according to the last national and international recommendations, during invasive life support strategies such as mechanical ventilation. Opioids manifest their sedative effect through activation of μ-opioid receptors, which are abundant both in the central and peripheral nervous system. Comparing fentanyl to morphine we can appreciate a much more powerful effect (75-220 major) with lower doses to obtain similar analgesic effect; these characteristics are due to the high lipophilicity of the molecule which easily crosses the blood-brain barrier (BBB). At the same time, fentanyl shows less adverse effects than morphine such as vomiting, nausea, gastrointestinal constipation, respiratory depression, dependence and tolerance. The drug is extensively metabolized by liver enzymes.

In routinary clinical practice it has been observed that large interindividual differences are found in the daily dosages needed to achieve pain control. Literature evidences that pharmacodynamic variation related to genotypes in receptor signalling or pain modulators may play an important role in this variability. Many genes are related to fentanyl pharmacodynamics and pharmacokinetics. Some polymorphism in these genes are already known to correlate with toxicity or efficacy of the drug, also in the paediatric population. More polymorphisms could be involved in abnormal pharmacodynamic or pharmacokinetics of fentanyl, therefore studies are necessary to better explain the possible role of pharmacogenetics in precision medicine especially in a very specific population as newborn.


Eligibility criteria: Inclusion Criteria:

1. all newborns on mechanical ventilation receiving fentanyl
2. parental written informed consent for participation in the study must be obtained

Exclusion Criteria:

1. Concurrent or previous opioid and/or midazolam administration (72 h interval required)
2. Known genetic or chromosomal anomaly
3. Probable rapid extubation

Primary outcomes:
measure: Identification of already described polymorphisms
timeFrame: Within 6 hours of fentanyl administration
measure: Identification of new polymorphisms
timeFrame: Within 6 hours of fentanyl administration
Secondary outcomes:
measure: To evaluate the statistical association between the polymorphisms identified and fentanyl dosage (µg/kg/hour)
timeFrame: Through study completion, an average of 18 months
Other outcomes:
Locations:
city: Trieste
country: Italy
facility: IRCCS Burlo Garofolo
Study officials:
affiliation: IRCCS materno infantile Burlo Garofolo
name: Laura Travan, MD
role: STUDY_DIRECTOR
References: