Dexmedetomidine versus Midazolam to shorten time on the ventilator in very preterm infants

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

This trial will test whether using dexmedetomidine instead of midazolam helps very preterm infants on invasive mechanical ventilation be extubated sooner.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 380 (estimated)
• Ages: N/A to 32 Weeks
• Sex: All
• Sponsor: Assistance Publique - Hôpitaux de Paris (other)
• Locations: 1 site (Paris)
• Trial ID: NCT06878703 on ClinicalTrials.gov

What this trial studies

This randomized phase 3 trial compares continuous intravenous dexmedetomidine infusion versus continuous intravenous midazolam infusion for sedation of very preterm neonates (<32 weeks gestation) who require invasive mechanical ventilation. Infants are randomized to receive a loading dose followed by a maintenance infusion within specified dose ranges for each drug while on ventilation, with care delivered in participating NICUs. The primary outcome centers on time to successful extubation and the protocol aims to enroll about 292 randomized patients (anticipating ~380 screened). Standard inclusion/exclusion and safety monitoring procedures are used to limit enrollment to clinically stable infants without contraindications to either agent.

Who should consider this trial

Good fit: Very preterm neonates born before 32 weeks' gestation with corrected age under 45 weeks who require sedation for invasive mechanical ventilation and whose parents provide informed consent.

Not a fit: Infants with hemodynamic instability, recent extubation, receiving contraindicated medications (e.g., clonidine or curare), or other contraindications to dexmedetomidine or midazolam are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, the dexmedetomidine arm could shorten duration of invasive ventilation and help reduce lung injury and rates of bronchopulmonary dysplasia by enabling earlier extubation.

How similar studies have performed: Small randomized and observational studies suggest dexmedetomidine is feasible and may cause less respiratory depression than benzodiazepines, but definitive phase 3 evidence in very preterm infants is limited.

Eligibility criteria

Inclusion Criteria:

* 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,

Exclusion Criteria:

* 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.

Where this trial is running

Paris

• Hospital Armand Trousseau, APHP Service : Department of Neonatology — Paris, France (RECRUITING)

Study contacts

• Principal investigator: Clément CHOLLAT, Doctor — Assistance Publique - Hôpitaux de Paris
• Study coordinator: Clément CHOLLAT, MD, PhD, Associate Professor

Conditions: PreTerm Neonate, Sedation for Invasive Mechanical Ventilation, Very Preterm Neonates With Sedation for Invasive Mechanical Ventilation, Mechanical ventilation, Sedative agent, Sedation-analgesia, Midazolam, Extubation