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

Phase 3

Completed

• Conditions: Mechanically-ventilated Neonates With Single-organ Respiratory Failure
• Interventions: Drug: Dexmedetomidine

• Registration Number: NCT01266252
• Lead Sponsor: University Hospital, Ghent

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.

Study Timeline

• Study First Submitted: 2010-12-22
• Study First Submitted QC: 2010-12-22
• Study First Posted: 2010-12-24
• Study Start: 2011-07-28
• Primary Completion: 2017-04-20
• Study Completion: 2018-04-10
• Status Verified: 2019-03
• Last Update Submitted: 2019-03-15
• Last Update Posted: 2019-03-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 35

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dexmedetomidine	Dexmedetomidine	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
level of analgosedation	72 hours	Preliminary knowledge on the level of analgosedation provided by dexmedetomidine.
safety issues	72 hours	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.
variability due to the Cytochrome P450 2A6 (CYP2A6) and Uridine diphosphate (UDP)-glucuronosyltransferase genotype	72 hours	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.

Trial Locations

Locations (3)

Ghent University Hospital; 🇧🇪 Ghent, Belgium

AZ Bruges; 🇧🇪 Bruges, Belgium

UZ Leuven; 🇧🇪 Leuven, Belgium