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

NCT06878703 | Recruiting Phase 3 DMC

• 1 other identifier: APHP230813
• Study Type: interventional
• Target: 380
• Locations: 1 country
• Sites: 1

Brief 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. 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. 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.

Conditions

PreTerm Neonate; Very Preterm Neonates With Sedation for Invasive Mechanical Ventilation; Sedation for Invasive Mechanical Ventilation

Keywords

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

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (6)

• Administration of Opioid Agents During Sedation with Dexmedetomidine or Midazolam in Neonatal Intensive Care.

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

• Quality of sedation

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

• Extubation failure 24 hours after extubation

  In 24 hours after extubation

• Withdrawal syndrome (Finnegan score >8).

  6 hours, within 7 days after extubation.

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

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

Other Outcomes (4)

• Exploratory outcome: Duration (in hours) of invasive mechanical ventilation from intubation to extubation

  From intubation to extubation

• Exploratory outcome: Length of stay in the NICU

  Within the limit of 24 months

• Exploratory outcome: : Short-term clinical outcomes

  at 36 Week of Gestation

Study Arms (2)

Midazolam

ACTIVE COMPARATOR

In 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.

Drug: Midazolam

Dexmedetomidine

EXPERIMENTAL

In 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).

Drug: Dexmedetomidine

Interventions

Dexmedetomidine DRUG

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)

Dexmedetomidine

Midazolam DRUG

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)

Midazolam

Eligibility Criteria

• Age: Up to 32 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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,
• 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,

You may not qualify if:

• 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.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• DrData: collaborator

Study Sites (1)

Hospital Armand Trousseau, APHP Service : Department of Neonatology

Paris, 75012, France

RECRUITING

MeSH Terms

Interventions

Midazolam; Dexmedetomidine

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Clément CHOLLAT, Doctor

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2025
• First Posted: March 17, 2025
• Study Start: October 16, 2025
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): October 16, 2029
• Last Updated: February 10, 2026

Record last verified: 2026-02

Locations

FR (1)