Double Blind, Multicenter, Randomized, Controlled Trial of Dexmedetomidine vs Placebo in Premature Neonates Receiving Invasive Ventilation
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 246
- 主要终点
- Dose of Opioids used
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Use of similar vials and labels for the 2 allocation arms. Masking of the result of randomization (arm description) in the eCRF. Only the treatment unit number will appear on the eCRF for administration.
入排标准
- 年龄范围
- — 至 10 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Above mentioned age limits (0 -10 weeks) apply to postnatal age. Inclusion criteria apply to gestational age at birth and postmenstrual age (in weeks).
- •Inclusion Criteria:
- •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
排除标准
- •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
结局指标
主要结局
Dose of Opioids used
时间窗: 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 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 hours, whichever comes last.
次要结局
- Number of days with paracetamol use(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)
- Percentage of time (hours) spent within an excessive/appropriate/ insufficient comfort/analgesia state based on the COMFORTneo scale(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(From inclusion to first planned extubation or unplanned extubation lasting at least 24 hours)
- Number of days with opioids and/or benzodiazepines(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(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(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(Within 7 days after the first planned extubation)
- Rate of unplanned extubation(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)(From inclusion to hospital discharge, assessed up to 24 weeks)
- Frequency of urinary retention episodes(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(Within 7 days of the first planned extubation or unplanned extubation lasting at least 24 hours)
- Number of Bradycardia episodes(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 hypotension episodes(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 anti-hypotensive treatments use(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 In-hospital deaths(At 36 weeks postmenstrual age)
- Number of In-hospital deaths(From the inclusion to hospital discharge or death, whichever comes first, assessed up to 24 weeks)
- Total duration of invasive ventilation(From the start of the investigational drug to hospital discharge or death, whichever comes first, assessed up to 24 weeks)
- Total duration of non-invasive ventilation(From the start of the investigational drug to hospital discharge or death, whichever comes first, assessed up to 24 weeks)
- Total duration of NICU stays(From the start of the investigational drug to hospital discharge or death, whichever comes first, assessed up to 24 weeks)
- Total duration Hospital stay(From the start of investigational drug to hospital discharge or death, whichever comes first, assessed up to 24 weeks)
- Number of patients presenting high-grade intraventricular hemorrhage Grade 3 and 4(From the start of investigational drug to hospital discharge or death, whichever comes first, assessed up to 24 weeks)
- Number of patients presenting periventricular leukomalacia(From the start of investigational drug to hospital discharge or death, whichever comes first, assessed up to 24 weeks)
- Number of patients presenting secondary sepsis(From the start of investigational drug to hospital discharge or death, whichever comes first, assessed up to 24 weeks)
- Number of patientsTreated for patent ductus arteriosus(From the start of investigational drug to hospital discharge or death, whichever comes first, assessed up to 24 weeks)
- Number of patients presenting bronchopulmonary dysplasia(At 36 weeks postmenstrual age)
- Number of patients presenting necrotizing enterocolitis(From the start of investigational drug to hospital discharge or death, whichever comes first, assessed up to 24 weeks)
- Number of patients presenting isolated intestinal perforation(From the start of investigational drug to hospital discharge or death, whichever comes first, assessed up to 24 weeks)
- Number of patients presenting treated retinopathy of prematurity(From the start of investigational drug to hospital discharge or death, whichever comes first, assessed up to 24 weeks)
- Long-term neurodevelopment using tests validated in French : Parent Report of Children's Abilities-Revised (PARCA-R)(At 2 years corrected age +/- 2 months)
- Long-term neurodevelopment using tests validated in French : BMT-i (Batterie Modulable de Tests informatisée, or "computerized Adaptable Test Battery")(At age 6 years +/- 2 months)