Dexmedetomidine in Mechanically Ventilated Neonates With Single-Organ Respiratory Failure.

Study Overview
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Brief Summary
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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
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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.

Official Title
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Dexmedetomidine Pharmacokinetics - Pharmacodynamics in Mechanically Ventilated Neonates With Single-organ Respiratory Failure (NEODEX).

Conditions
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Mechanically-ventilated Neonates With Single-organ Respiratory Failure

Intervention / Treatment
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* Drug: Dexmedetomidine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 1 Month

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dexmedetomidine<br> | Drug: Dexmedetomidine<br>* Dexmedetomidine will be given maximal 72 hours. In case analgosedation is still needed after stop of the dexmedetomidine infusion, the treatment is switched to conventional analgosedation regimens. Additional drugs are given to every inadequately sedated-painful patient (assessed by regular Comfort-neo and Numeric Rating Scale scoring). In case of oversedation or adverse drug events (hypotension, bradycardia), a downtitration (or stop) of the dexmedetomidine infusion is needed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pharmacokinetic parameters | Pharmacokinetic parameters of dexmedetomidine infusion in mechanically ventilated neonates with single-organ respiratory failure. | 72 hours | 
| Covariates | Covariates contributing to a variability in exposure and response to dexmedetomidine. | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| level of analgosedation | Preliminary knowledge on the level of analgosedation provided by dexmedetomidine. | 72 hours | 
| safety issues | Preliminary knowledge of safety issues concerning systolic and diastolic blood pressure, heart rate, respiratory rate, oxygen saturation, temperature are assessed baseline and at least per hour reassessed after starting the dexmedetomidine infusion. | 72 hours | 
| variability due to the Cytochrome P450 2A6 (CYP2A6) and Uridine diphosphate (UDP)-glucuronosyltransferase genotype | Knowledge of the contribution of the Cytochrome P450 2A6 (CYP2A6) and Uridine diphosphate (UDP)-glucuronosyltransferase genotype (covariate) to the variability in exposure and response to dexmedetomidine. | 72 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neonates, single organ respiratory failure