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

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.

Study Overview

• Status: Terminated
• Conditions: Respiratory Failure
• Intervention / Treatment: Drug: dexmedetomidine; Procedure: Vital signs; Procedure: blood sampling

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
  • Ghent, Belgium
    • University Hospital Ghent

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

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

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Investigators: Principal Investigator: Pieter De Cock, Pharm.D, University Hospital, Ghent

Publications and helpful links

Helpful Links

• website of University Hospital Ghent

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: February 25, 2010
• First Submitted That Met QC Criteria: February 25, 2010
• First Posted (Estimate): February 26, 2010

Study Record Updates

• Last Update Posted (Estimate): October 4, 2011
• Last Update Submitted That Met QC Criteria: October 3, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: Patients with single-organ failure in need of mechanical ventilation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: 2009/518