Dexmedetomidine Pharmacokinetics-pharmacodynamics in Mechanically Ventilated Children With Single-organ Respiratory Failure

Phase 3

Terminated

• Conditions: Respiratory Failure

• Registration Number: NCT01076816
• Lead Sponsor: University Hospital, Ghent

Brief Summary

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, we cannot simply extrapolate adult data for use in children but we are in need of data on pharmacokinetics and pharmacodynamics in every paediatric subpopulation.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-12
• Study First Submitted: 2010-02-25
• Study First Submitted QC: 2010-02-25
• Study First Posted: 2010-02-26
• Primary Completion: 2011-02
• Study Completion: 2011-05
• Status Verified: 2011-10
• Last Update Submitted: 2011-10-03
• Last Update Posted: 2011-10-04

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

Inclusion Criteria

• patients (m/f) admitted to the paediatric intensive care unit
• expected to require at least 24h of mechanical ventilation
• patient age : 1 month-15 years
• patients with single-organ respiratory failure

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 <72h
• patients with a known allergy to lorazepam, midazolam and/or morphine
• heart block
• pre-existing bradycardia
• hemodynamically unstable patients (Wernovsky index > 16 points) after full fluid replacement with crystalloid
• patients with significant renal insufficiency (creatinine plasma level 1 month-5 year : > 1 mg/dl ; 5-10 years : >1.2 mg/dl; > 10 years : > 1.5 mg/dl)
• patients with significant hepatic insufficiency (aspartate aminase >950 UI/L and prothrombin time < 60 or INR >1.4)
• previous treatment with α2-adrenoreceptor agonist clonidine within 14 days

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
pharmacokinetic parameters of dexmedetomidine infusion in mechanically ventilated children with single-organ respiratory failure	48 hours
covariates contributing to a variability in exposure and response to dexmedetomidine	48 hours

Secondary Outcome Measures

Name	Time	Method
preliminary knowledge on the level of sedation provided by dexmedetomidine	48 hours
preliminary knowledge of safety issues	48 hours	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
knowledge of the contribution of the CYP2A6 and UDP-glucuronosyltransferase genotype (covariate) to the variability in exposure and response to dexmedetomidine	48 hours

Trial Locations

Locations (2)

University Hospital Ghent; 🇧🇪 Ghent, Belgium

Cliniques Universitaires Saint-Luc; 🇧🇪 Brussels, Belgium