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PreTerm NeonatePhase 3DEXPRENCT06878703

Efficacy of Dexmedetomidine Versus Midazolam Sedation on Extubation Time in Mechanically Ventilated Preterm Infants

A Phase 3 study testing Midazolam and Dexmedetomidine in people with PreTerm Neonate and Sedation for Invasive Mechanical Ventilation, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

Very preterm neonates (born before 32 weeks' gestation) often require invasive mechanical ventilation (IMV) to manage respiratory insufficiency. In France, around 8,250 infants are born annually at <32 weeks, with an estimated 5,000 needing IMV. Read more about this study

Who is it for?
Ages Up to 32 weeks
What is being tested?
Midazolam and Dexmedetomidine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
380 participants
Where
1 siteFrance
Study dates
16 Oct 2025to 16 Oct 2029
Phase
Phase 3
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 Up to 32 weeks
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Patient admitted in NICU (intubated or not yet),
  • Gestational age at birth < 32 weeks of gestation (WG),
  • Corrected gestational age <45 weeks postmenstrual age Written or electronic informed consent signed by both parents.
  • Randomization Criteria :
  • Indication for sedation in the context of invasive mechanical ventilation,
  • Patient intubated or not yet,
Show all 15Show fewer
  • Elective sedation (acceptable delay between the decision to sedate and the administration of the sedative agent),
  • Presence or plan of a venous access,
  • No medical contraindication related to the administration of dexmedetomidine or midazolam,
  • No previous use of dexmedetomidine or midazolam within 48 hours, except for the sedation procedure for intubation,
  • No concomitant use of curare agent,
  • No clonidine treatment,
  • No previous extubation within 7 days,
  • No hemodynamic instability
  • No palliative care,

Who cannot join

  • Patient admitted in NICU (intubated or not yet),
  • Gestational age at birth < 32 weeks of gestation (WG),
  • Corrected gestational age <45 weeks postmenstrual age Written or electronic informed consent signed by both parents.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Clément CHOLLAT, MD, PhD, Associate Professor contact

+33 6 86 72 29 58

clement.chollat@aphp.fr

Stéphane MARRET, MD, PhD, Associate Professor contact

+33 2 32 88 64 22

stephane.marret@chu-rouen.fr

France1 site, 1 recruiting
  • Hospital Armand Trousseau, APHP Service : Department of Neonatology

    Paris, 75012

    Clément CHOLLAT, Doctor, +33 6 86 72 29 58, clement.chollat@aphp.fr

    Recruiting

Other trials in France

About this study

Official title: Efficacy of Dexmedetomidine Versus Midazolam Sedation on Extubation Time in Mechanically Ventilated Preterm Infants: a Randomized Controlled Multicenter Trial - DEXPRE

Very preterm neonates (born before 32 weeks' gestation) often require invasive mechanical ventilation (IMV) to manage respiratory insufficiency. In France, around 8,250 infants are born annually at <32 weeks, with an estimated 5,000 needing IMV. Although non-invasive support such as continuous positive airway pressure (CPAP) has become more common, a substantial proportion of these neonates still transition to IMV within the first few days of life. To reduce lung injury and the incidence of bronchopulmonary dysplasia (BPD), a key strategy in neonatal intensive care involves limiting the duration of IMV and promoting earlier extubation.

However, effective sedation and analgesia are essential for preterm infants subjected to intubation and mechanical ventilation. Traditionally, neonatologists combine a sedative (frequently midazolam) with an opioid (morphine, fentanyl, or sufentanil). Although these agents control pain and distress, they may cause respiratory depression, complicate weaning, and potentially contribute to adverse long-term outcomes. Midazolam, one of the few sedatives authorized for use in neonates, can improve comfort and sedation scores, but concerns persist about hypotension, altered cerebral perfusion, and a possible link to intraventricular hemorrhage (IVH). Moreover, combining benzodiazepines and opioids can prolong ventilation, increase the risk of complications, and impede timely extubation.

Read more

Rationale for Dexmedetomidine (DEX) Dexmedetomidine (DEX) is a highly selective α2-adrenergic agonist that offers sedative, anxiolytic, and analgesic properties with relatively minimal respiratory depression. Unlike certain other sedatives, DEX induces a state akin to natural sleep, allowing for easier arousal and potentially better respiratory drive. Animal studies suggest that DEX might be neuroprotective, reducing inflammation, oxidative stress, and apoptotic processes that can be detrimental to the developing brain. These features make DEX a promising alternative to the commonly used benzodiazepine-opioid regimens in very preterm neonates, who remain especially vulnerable to adverse drug effects.

Minimizing Invasive Mechanical Ventilation Reducing the time on IMV is crucial for preventing ventilator-induced lung injury and decreasing the likelihood of BPD. Early extubation is a central goal in this population, but sedation-related respiratory depression can thwart successful weaning and lead to reintubation. By preserving spontaneous breathing more effectively than midazolam or high-dose opioids, DEX may help neonates maintain adequate ventilation as they transition to non-invasive support. Furthermore, DEX's analgesic action could reduce the need for opioids, thereby mitigating withdrawal risks and other opioid-related complications such as feeding intolerance and extended hospital stays.

Objective of the DEXPRE Trial The objective of the DEXPRE trial is to compare the efficacy of dexmedetomidine-based sedation with that of midazolam-based sedation in very preterm neonates requiring IMV. Specifically, investigators aim to determine whether DEX can facilitate more rapid extubation and better overall respiratory outcomes compared to midazolam. By systematically evaluating sedation quality, respiratory stability, and potential side effects, the trial seeks to generate evidence that will guide future sedation protocols in neonatal intensive care units.

Read the detailed description

Hypothesis : the use of dexmedetomidine (DEX), 0.05 to 0.2 μg/kg/h, for very preterm neonates (<32 weeks' gestation, WG), requiring prolonged sedation throughout the period of invasive mechanical ventilation (IMV) (usually after intubation and until extubation), may improve weaning, and thus reduce extubation time in neonatal intensive care units.

Population of study participants : Very preterm neonate (gestational age at birth < 32 WG) with corrected gestational age <45 WG).

In the experimental group, neonates will receive dexmedetomidine via continuous intravenous infusion, starting with a 0.05 μg/kg loading dose over 30 minutes, followed by a maintenance dose ranging from 0.05 to 0.2 μg/kg per hour.

In the control group, neonates will receive midazolam via continuous intravenous infusion, starting with a 10 μg/kg loading dose over 30 minutes, followed by a maintenance dose ranging from 10 to 40 μg/kg per hour.

To achieve the randomization of 292 patients, an estimated enrollment of about 380 participants is anticipated, resulting in an allocation of 146 patients per study arm.

During the inclusion visit, after verifying the inclusion and exclusion criteria, an investigator will inform the parents of eligible neonates. If the neonate requires invasive mechanical ventilation and meets the randomization criteria, the investigator will proceed with the randomization.

According to the allocation arm, the nurse in charge of the patient will be able to prepare the experimental treatment using the kit provided by the hospital pharmacy.

The experimental treatment will start with a 30-minute loading dose, followed by a maintenance dose. The infusion rate will be adjusted according to medical prescriptions to achieve the desired sedation level, ranging from 0.1 mL/hr to 0.4 mL/hr. This treatment can be administered via any venous line, either peripheral or central.

Vital signs will be regularly recorded at 5, 10, 30, and 60 minutes, then at 2, 3, 6, and 12 hours after the start of treatment. Following this, recordings will be taken every 12 hours until the treatment ends.

Pain scores will be recorded 30 and 60 minutes after the initiation of treatment, and then every 3 hours, following standard practice.

On the day of extubation, routine data recording will include the timing and duration of experimental treatment and opioid interruptions, the extubation time, vital signs before and after treatment discontinuation, and any adverse events.

The final study visit will occur when the child reaches 2 years of corrected age +/- 2 months. At this visit, weight, height, head circumference, cerebral palsy status, age of walking acquisition, and the Ages \& Stages Questionnaire (ASQ) score will be recorded.

Keywords
Mechanical ventilation, Sedative agent, Sedation-analgesia, Midazolam, Extubation, Very preterm neonate, Dexmedetomidine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MidazolamDrug

    Continuous intravenous administration with a loading dose of 10 µg/kg over 30 min, followed by a maintenance dose (from 10 to 40 µg/kg/h)

  • DexmedetomidineDrug

    Continuous intravenous administration with a loading dose of 0.05 μg/kg over 30 minutes followed by a maintenance dose (from 0.05 to 0.2 μg/kg/h)

Study groups in NCT06878703
Study groupRoleWhat they receive
MidazolamActive comparatorIn the control group, neonates will receive midazolam intravenously, starting with a 10 μg/kg loading dose over 30 minutes, followed by a maintenance dose of 10-40 μg/kg/h.
Receives: Drug: Midazolam
DexmedetomidineExperimentalIn the experimental group, neonates will receive continuous intravenous administration of dexmedetomidine, with a loading dose of 0.05 μg/kg over 30 minutes followed by a continuous maintenance dose (from 0.05 to 0.2 μg/kg/hour).
Receives: Drug: Dexmedetomidine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time, measured in minutes, is evaluated from the discontinuation of the experimental treatment (either dexmedetomidine-based or midazolam-based sedation) to extubation.

    to compare the efficacy of dexmedetomidine-based sedation versus midazolam-based sedation in very preterm neonates.

    Measured: from the discontinuation of the experimental treatment to extubation (48 maximum)

Secondary outcomes (6)
  1. Administration of Opioid Agents During Sedation with Dexmedetomidine or Midazolam in Neonatal Intensive Care.

    Administration of opioid agents during the period of interest, i.e., from the start of treatment (DEX or midazolam) until extubation (total cumulative dose and morphine equivalents in mg/kg, duration). opioids include morphine (1), fentanyl (0.010), remifentanil (0.15), sufentanil (0.003) and methadone (0.3).

    Measured: from the start of treatment (dexmedetomidine or midazolam) until extubation (16 days maximum)

  2. Quality of sedation

    Time (in hours) between start of sedation and achievement of a normal Comfort B score (ie. between 11 and 17),

    Measured: Before sedation, then every 30 min after sedation initiation, then every 3 hours after the initial 60 min, and up to 14 days

  3. Extubation failure 24 hours after extubation

    Intubation proportion at 24 hours after extubation.

    Measured: In 24 hours after extubation

  4. Withdrawal syndrome (Finnegan score >8).

    Proportion of patients with at least one value of the Finnegan score > 8 from within 3 days after extubation.

    Measured: 6 hours, within 7 days after extubation.

  5. Hemodynamic and respiratory adverse effects between inclusion and 84 hours after treatment discontinuation,

    • Bradycardia defined by heart rate < 80 bpm considered as clinically significant by the treating physician, despite optimization of hemodynamic management
    • Hemodynamic instability defined by a mean blood pressure below corrected GA, or a skin recoloration time > 3 seconds despite optimization of haemodynamic management
    • Desaturation <85% despite optimization of mechanical ventilation
    • Reintubation

    Measured: From start of the sedation until 84 h after the sedative is stopped (maximum 18 days)

  6. In hospital morbi mortality.

    Severe neonatal morbidity as :

    • late onset sepsis defined by a positive blood culture and antibiotic therapy more than 72 hours,
    • necrotizing enterocolitis according to Bell's definition61
    • moderate (fraction of inspired oxygen (FiO2) <30%) and severe (FiO2 ≥30%) bronchopulmonary dysplasia at 36 WG defined by need of IMV, nasal continuous positive airway pressure, or nasal cannula at 36 weeks postmenstrual age, according to Jobe's definition
    • retinopathy of prematurity is diagnosed at the fundus performed systematically before discharge, intraventricular hemorrhage diagnosed on routine transfontanelar ultrasound, according to Papile classification

    Measured: the period of hospitalization and within the limit of 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Mar 2025
  2. Study start16 Oct 2025
  3. Primary completion30 Dec 2027 (estimated)
  4. Study completion16 Oct 2029 (estimated)

Resources

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 3
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
380 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06878703
Sponsor's protocol ID
APHP230813
Acronym
DEXPRE
Status last verified
Feb 2026
First submitted
21 Feb 2025
Last updated
10 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Midazolam and Dexmedetomidine in people with PreTerm Neonate and Sedation for Invasive Mechanical Ventilation, run by Assistance Publique - Hôpitaux de Paris at 1 site 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 15 inclusion and 3 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 10 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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 Clément CHOLLAT, MD, PhD, Associate Professor (+33 6 86 72 29 58, clement.chollat@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time, measured in minutes, is evaluated from the discontinuation of the experimental treatment (either dexmedetomidine-based or midazolam-based sedation) to extubation. (time frame: from the discontinuation of the experimental treatment to extubation (48 maximum)). 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 10 Feb 2026.

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