Pharmacokinetics-pharmacodynamics of Morphine With or Without Midazolam Administered by Continuous Infusion in Neonatal Intensive Care

NCT05371886 | Recruiting

• 1 other identifier: PHARAONIC
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 5

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.

Conditions

Sedation Complication; Mechanical Ventilation in Neonates

Keywords

morphine, midazolam; pharmacokinetics; pharmacodynamics; analgesia; neonates

Outcome Measures

Primary Outcomes (1)

• Effective dose for 50% of patients (ED50 ) of morphine in continuous infusion in neonates ventilated in the neonatal intensive care unit

  To evaluate which dose is effective, cComfort will be assessed with COMFORTneo score (scale from 6 to 30 with decreasing score with increasing comfort). The dose-response relationship will be assessed with the correlation between a comfortable score (between 11 and 13) and the effective dose for 50% of patients (ED50), by PKPD modeling

  From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks

Secondary Outcomes (6)

• Clearance (ml/min/kg) of morphine and midazolam

  From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks

• Volume of distribution (L/kg) of morphine and midazolam

  From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks

• Concentration of morphine

  From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks

• Concentration of midazolam

  From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks

• Doses of morphine and midazolam (µg/kg/h)

  From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks

Study Arms (1)

Dose-effect relationship of morphine +/- midazolam administration

OTHER

Other: Dose-effect relationship of morphine +/- midazolam administration

Interventions

Dose-effect relationship of morphine +/- midazolam administration OTHER

Dose-effect relationship of morphine +/- midazolam administration as continuous infusion in neonates undergoing mechanical ventilation through PKPD modelling

Dose-effect relationship of morphine +/- midazolam administration

Eligibility Criteria

• Age: 20 Weeks - 45 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Hospitalier Intercommunal Creteil: lead

Study Sites (5)

CHRU Morvan

Brest, 29609, France

RECRUITING

CH SUD Francilien

Corbeil-Essonnes, 91100, France

RECRUITING

CHI Créteil

Créteil, 94000, France

RECRUITING

CHU Lille

Lille, France

RECRUITING

CHU Tours

Tours, France

RECRUITING

MeSH Terms

Conditions

Agnosia

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Manon TAUZIN, MD

CONTACT

01 45 17 50 00; manon.tauzin@chicreteil.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 31, 2022
• First Posted: May 12, 2022
• Study Start: April 1, 2023
• Primary Completion: July 1, 2023
• Study Completion (Estimated): May 1, 2027
• Last Updated: November 17, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5)