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

March 26, 2024 updated by: Centre Hospitalier Intercommunal Creteil
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.).

Study Type

Interventional

Enrollment (Estimated)

180

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Brest, France, 29609
      • Corbeil-Essonnes, France, 91100
        • Not yet recruiting
        • CH Sud Francilien
        • Contact:
        • Principal Investigator:
          • Hasinirina RAZAFIMAHEFA, MD
      • Créteil, France, 94000

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 hour to 4 weeks (Child)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Dose-effect relationship of morphine +/- midazolam administration
Other: Dose-effect relationship of morphine +/- midazolam administration
Dose-effect relationship of morphine +/- midazolam administration as continuous infusion in neonates undergoing mechanical ventilation through PKPD modelling

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effective dose for 50% of patients (ED50 ) of morphine in continuous infusion in neonates ventilated in the neonatal intensive care unit
Time Frame: From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clearance (ml/min/kg) of morphine and midazolam
Time Frame: From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
Morphine and midazolam serum levels (mg/L) will be used to describe clearance by PKPD
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
Time Frame: From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
Morphine and midazolam serum levels (mg/L) will be used to describe volume of distribution by PKPD modeling
From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
Concentration of morphine
Time Frame: From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
Morphine serum levels (mg/L) will be used to describe inter-individual variability by PKPD modeling
From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
Concentration of midazolam
Time Frame: From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
midazolam serum levels (mg/L) will be used to describe inter-individual variability by PKPD modeling
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)
Time Frame: From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
PKPD models will be used to simulate doses to determine optimal doses required according to gestational age, postnatal age, corrected age, weight and clinical context
From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
To assess pain responses by the Newborn Infant Parasympathetic Evaluation (NIPE) index
Time Frame: From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
NIPE Index which provides an observer-independent, quantitative assessment of comfort and analgesia based on analysis of heart rate variability. The NIPE Index ranges from 0 to 100 with increasing index with increasing comfort
From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Hospitalier Intercommunal Creteil

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2023

Primary Completion (Actual)

July 1, 2023

Study Completion (Estimated)

July 1, 2025

Study Registration Dates

First Submitted

January 31, 2022

First Submitted That Met QC Criteria

May 10, 2022

First Posted (Actual)

May 12, 2022

Study Record Updates

Last Update Posted (Actual)

March 27, 2024

Last Update Submitted That Met QC Criteria

March 26, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PHARAONIC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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