Dexmedetomidine for Invasive Ventilation In the NEOnate

Официальное название

Double Blind, Multicenter, Randomized, Controlled Trial of Dexmedetomidine vs Placebo in Premature Neonates Receiving Invasive Ventilation

Обзор

Despite the increasing use of non-invasive ventilation, a large majority of premature neonates still receive invasive ventilation during their NICU (neonatal intensive care unit) stay. Invasive ventilation is a unanimous source of discomfort and pain. As opposed to the adult and pediatric population, routine use of opioids or midazolam is not recommended in ventilated neonates. Although opioids are the most frequently prescribed analgosedative drugs in ventilated premature neonates, their use is controversial because of the risk of respiratory depression - which can prolong invasive ventilation- and concerns on long-term neurodevelopment. Dexmedetomidine, a selective alpha-2- adrenergic agonist routinely used in the adult ICU (intensive care unit), provides light sedation and some analgesia with no or little respiratory-depression effect. It also has neuroprotective properties after pediatric cardiac surgery and in neonatal animal models. Dexmedetomidine is thus a promising candidate drug in ventilated premature neonates that might reduce the duration of mechanical ventilation and preserve neurodevelopment in this vulnerable population. The investigators hypothesize that the use of dexmedetomidine in ventilated premature neonates could decrease the need for opioids, facilitate extubation and thereby preserve long-term neurodevelopmental outcome.

Вмешательства

• Препарат Dexmedetomidine Injectable Solution
  Intravenous administration for maximum 20 days
• Препарат Glucose 5% Injectable Solution
  Intravenous administration for maximum 20 days

Первичные конечные точки

• Dose of Opioids used [Срок оценки: From the start of the investigational drug to the cessation of any opioid or of the investigational drug for at least 24 hours, whichever comes last]

Вторичные конечные точки (12)

• Percentage of time (hours) spent within an excessive/appropriate/ insufficient comfort/analgesia state based on the COMFORTneo scale [Срок оценки: From the start of the investigational drug to the cessation of any opioid or of the investigational drug for at least 24 hours, whichever comes last]
• Duration of invasive ventilation in hours [Срок оценки: From inclusion to first planned extubation or unplanned extubation lasting at least 24 hours]
• Number of days with opioids and/or benzodiazepines [Срок оценки: From the start of the investigational drug to the cessation of any opioid or of the investigational drug for at least 24 hours, whichever comes last]
• Cumulative dose of midazolam or other benzodiazepines [Срок оценки: From the start of the investigational drug to the cessation of any opioid or of the investigational drug for at least 24 hours, whichever comes last]
• Number of days with paracetamol use [Срок оценки: From the start of the investigational drug to the cessation of any opioid or of the investigational drug for at least 24 hours, whichever comes last]
• Frequency of muscle blocker use to improve ventilation [Срок оценки: From the start of the investigational drug to the cessation of any opioid or of the investigational drug for at least 24 hours, whichever comes last]
• Rate of extubation failure [Срок оценки: Within 7 days after the first planned extubation]
• Rate of unplanned extubation [Срок оценки: From the start of the investigational drug to the cessation of any opioid or of the investigational drug for at least 24 hours, whichever comes last]
• Age at full enteral feeding in postmenstrual age (weeks) [Срок оценки: From inclusion to hospital discharge, assessed up to 24 weeks]
• Frequency of urinary retention episodes [Срок оценки: From the start of the investigational drug to the cessation of any opioid or of the investigational drug for at least 24 hours, whichever comes last]
• Finnegan neonatal withdrawal scale or any other validated withdrawal scale [Срок оценки: Within 7 days of the first planned extubation or unplanned extubation lasting at least 24 hours]
• Number of Bradycardia episodes [Срок оценки: From the start of the investigational drug to the cessation of any opioid or of the investigational drug for at least 24 hours, whichever comes last]

Критерии участия

Above mentioned age limits (0 -10 weeks) apply to postnatal age. Inclusion criteria apply to gestational age at birth and postmenstrual age (in weeks).

Критерии включения

• Neonates with a gestational age at birth < 32 weeks of gestation and corrected gestational age < 32 weeks postmenstrual age
• Invasively ventilated with an expected or effective duration of ventilation > 24 hours at inclusion
• Under mechanical ventilation since less than 72 hours at inclusion
• With parental consent
• Affiliated to or benefiting from a social security system

Критерии исключения

• Previous inclusion in this trial
• Participation in another trial including analgesics or sedatives
• Ongoing palliative care
• Administration of dexmedetomidine or another alpha-2 agonist in the 96 previous hours
• 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
• Pulmonary hypertension requiring pharmacological treatment
• Heart rate <100 bpm
• Hepatic impairment defined as alanine aminotransferase level > 2 x normal upper limit
• Known contra-indications to dexmedetomidine: hypersensitivity, atrioventricular block, acute cerebrovascular event
• Hypersensitivity to the active substance or to any of the excipients contained in the medicine

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Франция · 12 центров

• CHU Brest - Hôpital Morvan — Brest
• Centre Hospitalier Intercommunal de Créteil — Créteil
• CHU Grenoble Alpes — Grenoble
• CHRU Lille — Lille
• CHU Limoges — Limoges
• CHU de Nantes — Nantes
• CHU de Nice — Nice
• AP-HP Hôpital Necker Enfants Malades — Paris
• … и ещё 4 центра

Идентификаторы

NCT: NCT07493785 · DIVINEO

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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