Double blind, multicenter, randomized, controlled trial of dexmedetomidine vs placebo in premature neonates receiving invasive ventilation

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Intercommunal Creteil

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03], Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Decision date (initial)

2026-02-18

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Direction générale de l'Offre de soins (DGOS)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To assess the effect of continuous intravenous infusion of dexmedetomidine vs placebo on the cumulative opioids’ doses (including continuous infusion and boluses) in ventilated premature neonates with an expected or effective duration of ventilation of at least 24h.

Secondary objectives 16

1. To assess efficacy using with the percentage of time spent within an appropriate comfort/analgesia state (COMFORTneo scale) during invasive ventilation
2. To assess efficacy using the duration of invasive ventilation for the studied episode
3. To assess efficacy using the frequency of opioid-related adverse effects
4. To assess efficacy using the cumulative dose of benzodiazepines during the studied episode
5. To assess efficacy using the number of days with opioids or benzodiazepines (continuous or boluses)
6. To assess efficacy using the frequency of muscle blocker use
7. To assess efficacy using the rate of reintubation within 7 days after the first planned extubation
8. To assess efficacy using the rate of unplanned extubations
9. To assess tolerance and safety using frequency and severity of hemodynamic adverse events
10. To assess tolerance and safety using the frequency of opioids’ withdrawal syndrome (Finnegan score)
11. To assess tolerance and safety using In-hospital mortality
12. To assess tolerance and safety using the total duration of invasive ventilation during hospital stay
13. To assess tolerance and safety using the total duration of non-invasive ventilation during hospital stay
14. To assess tolerance and safety using the total duration of NICU and hospital stay
15. To assess tolerance and safety using the severe neonatal morbidity at 36 weeks postmenstrual age and at discharge from hospital
16. To assess tolerance and safety using the neurodevelopment at age 2 and 6

Conditions and MedDRA coding

Neonatal respiratory distress. Pain and discomfort

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Neonates with a gestational age at birth < 32 weeks of gestation and corrected gestational age < 32 weeks postmenstrual age
2. Invasively ventilated with an expected or effective duration of ventilation > 24h at inclusion
3. Under mechanical ventilation since less than 72h at inclusion
4. With parental consents
5. Affiliated to or benefiting from a social security system

Exclusion criteria 10

1. Previous inclusion in this trial
2. Participation in another trial including analgesics or sedatives
3. Ongoing palliative care
4. Administration of dexmedetomidine or another alpha-2 agonist in the 96 previous hours
5. Hemodynamic compromise defined as any of: poor perfusion (increased capillary refill time, oliguria); hypotension defined as a mean blood pressure in mm Hg < postmenstrual age in weeks; ongoing inotropic treatment with dopamine or dobutamine ≥ 5 µg/kg/min, or any other inotropic drug at any dose, or need for more than one volume expansion (20 ml/kg) in the 6 previous hours
6. Pulmonary hypertension requiring pharmacological treatment
7. Heart rate <100 bpm
8. Hepatic impairment defined as alanine aminotransferase level > 2x normal upper limit
9. Known contra-indications to dexmedetomidine: hypersensitivity, atrioventricular block, acute cerebrovascular event
10. Hypersensitivity to the active substance or to any of the excipients contained in the medicine

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Cumulative dose of opioids (morphine, sufentanil, fentanyl) converted to equivalent morphine dose in µg/kg using fixed equipotency ratios based on national prescriptions habits, administered during the studied period defined as the time between the start of the investigational drug and the cessation of any opioid or of the investigational drug for at least 24 h, whichever comes last.

Secondary endpoints 5

1. Pain and comfort outcomes: COMFORTneo pain and comfort scale, number of days with opioids and/or benzodiazepines, cumulative dose of midazolam (µg/kg), frequency of muscle blocker use;
2. Opioids’ adverse effects: age at full enteral feeding, urinary retention, Finnegan neonatal withdrawal scale, duration of invasive ventilation, extubation failure at 3 and 7 days after extubation, unplanned extubation
3. Dexmedetomidine’s tolerance: bradycardia (heart rate < 100/min for 5 consecutive minutes with SpO2> lower threshold for postmenstrual age), hypotension (mean arterial blood pressure in mmHg < postmenstrual age in weeks), anti-hypotensive treatments use
4. Safety outcomes at discharge: in-hospital mortality, total duration of invasive and non-invasive ventilation, total duration of NICU and hospital stay, high-grade intraventricular hemorrhage, periventricular leukomalacia, secondary sepsis, treated patent ductus arteriosus, bronchopulmonary dysplasia at 36 weeks postmenstrual age, necrotizing enterocolitis, isolated intestinal perforation, treated retinopathy of prematurity.
5. Long-term neurodevelopment using tests validated in French: Parent Report of Children's Abilities-Revised (PARCA-R) at age 2 and BMT-i (Batterie Modulable de Tests informatisée, or "computerized Adaptable Test Battery") at age 6

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Intercommunal Creteil

Sponsor organisation

Centre Hospitalier Intercommunal Creteil

Address

40 Avenue De Verdun

City

Creteil

Postcode

94000

Country

France

Scientific contact point

Organisation

Centre Hospitalier Intercommunal Creteil

Contact name

Xavier DURRMEYER

Public contact point

Organisation

Centre Hospitalier Intercommunal Creteil

Contact name

Centre Hospitalier Intercommunal de Créteil

Locations

1 EU/EEA country · 12 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications