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

NCT01076816 | Terminated Phase 3 DMC

• 1 other identifier: 2009/518
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 2

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.

Conditions

Respiratory Failure

Keywords

Patients with single-organ failure in need of mechanical ventilation

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• preliminary knowledge on the level of sedation provided by dexmedetomidine

  48 hours

• preliminary knowledge of safety issues

  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

Interventions

dexmedetomidine DRUG

dexmedetomidine will be given max 48h. 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 patient (assessed by regular Comfort scoring). In case of oversedation or adverse drug events (hypotension, bradycardia), a downtitration (or stop) of the dexmedetomidine infusion is needed.

Vital signs PROCEDURE

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.

blood sampling PROCEDURE

Blood sampling for pharmacokinetic modelling is limited to a maximum of 1,8 ml/kg (in line with the EMEA guidelines on maximum blood sampling in children). Pharmacokinetic parameters and influence of covariates on these parameters will be assessed by a population pharmacokinetic approach.

Eligibility Criteria

• Age: 1 Month - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• patients with neurologic conditions that prohibit an evaluation of adequate analgosedation
• 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

Sponsors & Collaborators

• University Hospital, Ghent: lead

Study Sites (2)

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

University Hospital Ghent

Ghent, Belgium

Location

Related Links

• website of University Hospital Ghent

MeSH Terms

Conditions

Respiratory Insufficiency

Interventions

Dexmedetomidine; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Pieter De Cock, Pharm.D

  University Hospital, Ghent

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2010
• First Posted: February 26, 2010
• Study Start: December 1, 2009
• Primary Completion: February 1, 2011
• Study Completion: May 1, 2011
• Last Updated: October 4, 2011

Record last verified: 2011-10

Locations

BE (2)