Clinical trial NCT01266252: Dexmedetomidine in Mechanically Ventilated Neonates With Single-Organ Respiratory Failure.
Official title: Dexmedetomidine Pharmacokinetics - Pharmacodynamics in Mechanically Ventilated Neonates With Single-organ Respiratory Failure (NEODEX).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Mechanically-ventilated Neonates With Single-organ Respiratory Failure
Keywords: neonates
single organ respiratory failure
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
Collaborators: name: Orion Corporation, Orion Pharma
First posted: 2010-12-24
Enrollment: 35
Sex: ALL
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Clinical experience with dexmedetomidine in the paediatric population is limited. Critical illness can affect drug pharmacokinetics and -dynamics; the investigators cannot simply extrapolate adult data for use in children but the investigators are in need of data on pharmacokinetics and pharmacodynamics in every paediatric subpopulation.

Detailed description: Currently, dexmedetomidine is approved by the United States Food and Drug Administration (FDA) for short-term analgosedation (\<24h) in mechanically-ventilated critical care adult patients and sedation of non-intubated adult patients prior to and/or during surgical and other procedures. Trials are underway to investigate its pharmacokinetics, clinical efficacy and safety in long-term use. Clinical experience with dexmedetomidine in the paediatric population is limited. Moreover, during childhood many developmental changes take place with consequences on drug exposure and drug response. Finally, critical illness itself can affect drug pharmacokinetics and -dynamics. Therefore, the investigators cannot simply extrapolate adult data for use in children but the investigators are in need of data on pharmacokinetics and pharmacodynamics in every paediatric subpopulation.

Eligibility criteria: Inclusion Criteria:

* patient age less than 1 month (Male/Female) (step-down strategy for age)

  * first included patients (n=30): postmenstrual age \>= 34 weeks (near-term neonates)
  * following included patients (n=30) : postmenstrual age \>= 25 weeks and \< 34 weeks (preterm neonates)
* patients with single-organ respiratory failure in need for analgosedation (guidance : Comfort neo score \>14 or Numeric Rating Scale (NRS) score Pain (P)/Comfort (C)\>4)
* patients admitted to the neonatal intensive care unit
* expected to require at least 20 hours of mechanical ventilation

Exclusion Criteria:

* patients with neurologic conditions that prohibit an evaluation of adequate analgosedation
* no arterial catheter in place at inclusion
* patients who have received another investigational drug within 30 days
* patients on continuous infusion with neuromuscular blockers
* patients with a life expectancy \<72 hours
* patients with a known allergy to fentanyl
* congenital or acquired heart block (grade 3)
* sustained bradycardia
* haemodynamically unstable patients (definition : Mean Arterial Pressure (MAP) lower than : postmenstrual age (in weeks) - 5 millimeter Hg, eventually under dopamine infusion max. 16 mcg/kilogram/minute and/or dobutamine infusion maximal 16 mcg/kilogram/minute)
* patients with significant renal insufficiency (creatinine plasma level \>1.5 milligram/deciliter)
* patients with significant hepatic insufficiency (as estimated by local investigators)
* previous treatment with α2-adrenoreceptor agonist clonidine within 14 days
* absence of parental consent

Primary outcomes:
measure: pharmacokinetic parameters
timeFrame: 72 hours
measure: Covariates
timeFrame: 72 hours
Secondary outcomes:
measure: level of analgosedation
timeFrame: 72 hours
measure: safety issues
timeFrame: 72 hours
measure: variability due to the Cytochrome P450 2A6 (CYP2A6) and Uridine diphosphate (UDP)-glucuronosyltransferase genotype
timeFrame: 72 hours
Other outcomes:
Locations:
city: Bruges
country: Belgium
facility: AZ Bruges
city: Ghent
country: Belgium
facility: Ghent University Hospital
city: Leuven
country: Belgium
facility: UZ Leuven
Study officials:
affiliation: University Hospital, Ghent
name: Koenraad Smets, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: