Clinical trial NCT05371886: Pharmacokinetics-pharmacodynamics of Morphine With or Without Midazolam Administered by Continuous Infusion in Neonatal Intensive Care
Official title: Pharmacokinetics-pharmacodynamics of Morphine With or Without Midazolam Administered by Continuous Infusion in Neonatal Intensive Care
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Sedation Complication
Mechanical Ventilation in Neonates
Keywords: morphine, midazolam
pharmacokinetics
pharmacodynamics
analgesia
neonates
Lead sponsor: Centre Hospitalier Intercommunal Creteil
Sponsor class: OTHER
First posted: 2022-05-12
Enrollment: 180
Sex: ALL
Minimum age (years): 20
Maximum age (years): 45
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The main objective is to estimate a dose-effect relationship of morphine +/- midazolam administration as continuous infusion in neonates undergoing mechanical ventilation through PKPD modelling.
Primary purpose: SUPPORTIVE_CARE

Brief summary: This study aims to describe a dose-effect relationship of morphine alone and morphine and midazolam administered as continuous infusion in neonates hospitalized in Neonatal intensive care unit and undergoing mechanical ventilation, through PKPD modelling.

Detailed description: This study will include all neonates receiving a sedo-analgesia with continuous infusion of morphine alone or morphine and midazolam during mechanical ventilation in 3 French NICUs. Comfort and pain will be assessed by COMFORTneo pain scores and Newborn Infant Parasympathetic Evaluation Index. Morphine, midazolam and their metabolites' concentrations will be determined on samples taken during a planned blood test. Through PKPD modelling, the dose-concentration-effect relationships will be found and interindividual variability of these drugs in neonates and simulate doses needed to achieve comfort in neonates according to their individual characteristics (gestational age, post-natal age, weight etc.).

Eligibility criteria: Inclusion Criteria:

* Neonates \< 45 weeks of corrected gestational age
* Hospitalized in a Neonatal Intensive Care Unit
* Undergoing mechanical ventilation
* Patients that receive morphine alone or morphine and midazolam as continuous infusion
* Affiliated to a social security system

Exclusion Criteria:

* Current weight \< 600g
* Neonates under palliative care
* Therapeutic hypothermia for perinatal anoxia
* Neonates who underwent a surgical procedure during the past 72 hours
* Neonates receiving concomitantly a paralytic or another drug for sedation or analgesia other than morphine or midazolam (except for paracetamol/acetaminophen)
* Parents refusing that their child participate

Primary outcomes:
measure: Effective dose for 50% of patients (ED50 ) of morphine in continuous infusion in neonates ventilated in the neonatal intensive care unit
timeFrame: From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
Secondary outcomes:
measure: Clearance (ml/min/kg) of morphine and midazolam
timeFrame: From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
measure: Volume of distribution (L/kg) of morphine and midazolam
timeFrame: From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
measure: Concentration of morphine
timeFrame: From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
measure: Concentration of midazolam
timeFrame: From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
measure: Doses of morphine and midazolam (µg/kg/h)
timeFrame: From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
measure: To assess pain responses by the Newborn Infant Parasympathetic Evaluation (NIPE) index
timeFrame: From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
Other outcomes:
Locations:
city: Brest
country: France
facility: CHRU Morvan
city: Corbeil-Essonnes
country: France
facility: CH SUD Francilien
city: Créteil
country: France
facility: CHI Créteil
city: Lille
country: France
facility: CHU Lille
city: Tours
country: France
facility: CHU Tours
Study officials:
References: