Sedation ComplicationNCT05371886
Pharmacokinetics-pharmacodynamics of Morphine With or Without Midazolam Administered by Continuous Infusion in Neonatal Intensive Care
A study testing Dose-effect relationship of morphine +/- midazolam administration in people with Sedation Complication and Mechanical Ventilation in Neonates, run by Centre Hospitalier Intercommunal Creteil at 5 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 45 weeks
- Conditions the study is for
- Sedation Complication, Mechanical Ventilation in Neonates
- What is being tested?
- Dose-effect relationship of morphine +/- midazolam administration
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 180 participants
- Where
- 5 sitesFrance
- Study dates
- 1 Apr 2023to 1 May 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 45 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
France5 sites, 5 recruiting
- Recruiting
CHRU Morvan
Brest, 29609
Jean Michel ROUE, MD, jean-michel.roue@chu-brest.fr
Jean MIchel ROUE, MD
- Recruiting
CH SUD Francilien
Corbeil-Essonnes, 91100
Hasinirina RAZAFIMAHEFA, MD, hasinirina.razafimahefa@chsf.fr
Hasinirina RAZAFIMAHEFA, MD
- Recruiting
CHI Créteil
Créteil, 94000
Manon TAUZIN, MD, manon.tauzin@chicreteil.fr
Manon TAUZIN, MD
- Recruiting
CHU Lille
Lille
Boukhris Riadh, MD, riadh.boukhris@chu-lille.fr
- Recruiting
CHU Tours
Tours
LOOSE Anne, MD, a.loose@chu-tours.fr
About this study
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.
Read the 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.).
- Being tested
- Dose-effect relationship of morphine +/- midazolam administration
- Keywords
- morphine, midazolam, pharmacokinetics, pharmacodynamics, analgesia, neonates
- Medical subject headings
- Agnosia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dose-effect relationship of morphine +/- midazolam administrationOther
Dose-effect relationship of morphine +/- midazolam administration as continuous infusion in neonates undergoing mechanical ventilation through PKPD modelling
| Study group | Role | What they receive |
|---|---|---|
| Dose-effect relationship of morphine +/- midazolam administration | Other | Not described Receives: Other: Dose-effect relationship of morphine +/- midazolam administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Morphine and midazolam serum levels (mg/L) will be used to describe clearance by PKPD
Measured: 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
Morphine and midazolam serum levels (mg/L) will be used to describe volume of distribution by PKPD modeling
Measured: From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
Concentration of morphine
Morphine serum levels (mg/L) will be used to describe inter-individual variability by PKPD modeling
Measured: From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
Concentration of midazolam
midazolam serum levels (mg/L) will be used to describe inter-individual variability by PKPD modeling
Measured: 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)
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
Measured: 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
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
Measured: From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2022
- Study start1 Apr 2023
- Primary completion1 Jul 2023
- Study completion1 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sedation ComplicationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- 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.
- Masking
- None (open label)
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Intercommunal Creteil
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05371886
- Sponsor's protocol ID
- PHARAONIC
- Status last verified
- Nov 2025
- First submitted
- 31 Jan 2022
- Last updated
- 17 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics-pharmacodynamics of Morphine With or Without Midazolam Administered by Continuous Infusion in Neonatal Intensive Care
- ClinicalTrials.gov ID
- NCT05371886
- Acronym / sponsor ID
- PHARAONIC
- Keywords
- morphine, midazolam, pharmacokinetics, pharmacodynamics, analgesia, neonates
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- Centre Hospitalier Intercommunal CreteilUniversity, hospital or other
- Study start
- 1 Apr 2023 (actual)
- Primary completion
- 1 Jul 2023 (actual)
- Study completion
- 1 May 2027 (estimated)
- First posted
- 12 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.).
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Dose-effect relationship of morphine +/- midazolam administration | Other | Other: Dose-effect relationship of morphine +/- midazolam administration |
Who may qualify
- Ages
- 20 to 45 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dose-effect relationship of morphine +/- midazolam administrationDose-effect relationship of morphine +/- midazolam administration as continuous infusion in neonates undergoing mechanical ventilation through PKPD modelling | Other | Dose-effect relationship of morphine +/- midazolam administration |
Primary outcome
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
6 secondary outcomes
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
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
Concentration of morphine
Time frame: 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
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
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dose-effect relationship of morphine +/- midazolam administration in people with Sedation Complication and Mechanical Ventilation in Neonates, run by Centre Hospitalier Intercommunal Creteil at 5 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Manon TAUZIN, MD (01 45 17 50 00 ext. 9479, manon.tauzin@chicreteil.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Nov 2025.