Pharmacogenetics Analysis of Fentanyl Administered in Newborns

Newborn Clinical Trial

Official title:

Pharmacogenetics Analysis in Newborn Patients on Mechanical Ventilation and Fentanyl Administration

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05805241
• Other study ID #: RC 31/22
• Status: Recruiting
• Start date: February 7, 2023
• Est. completion date: March 15, 2026

Study information

• Verified date: April 2023
• Source: IRCCS Burlo Garofolo
• Contact: Laura Travan, MD
• Phone: +390403785505
• Email: laura.travan[@]burlo.trieste.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 66
• Est. completion date: March 15, 2026
• Est. primary completion date: March 15, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Day to 28 Days

Eligibility

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

Related Conditions & MeSH terms

• Fentanyl
• Newborn
• Pharmacogenetics

Locations

Country	Name	City	State
Italy	IRCCS Burlo Garofolo	Trieste

Sponsors (1)

Lead Sponsor	Collaborator
IRCCS Burlo Garofolo

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identification of already described polymorphisms	To identify candidate polymorphisms based on the literature explaining interindividual variability in the pharmacokinetics and pharmacodynamics of fentanyl. 1 cc of blood sample will be collected	Within 6 hours of fentanyl administration
Primary	Identification of new polymorphisms	To identify new polymorphisms explaining interindividual variability in the pharmacokinetics and pharmacodynamics of fentanyl. 1 cc of blood sample will be collected.	Within 6 hours of fentanyl administration
Secondary	To evaluate the statistical association between the polymorphisms identified and fentanyl dosage (µg/kg/hour)	Association study. The univariate statistical analysis will consider the dose of fentanyl (µg/kg/hour) as a continuous dependent variable, associating it with the candidate genotypes (independent variables) by means of t-tests. The association of fentanyl dose with genotypes will also be evaluated in a multivariate model, adjusted for relevant demographic and clinical covariates, using generalized linear models.	Through study completion, an average of 18 months