Clinical trial NCT01076816: Dexmedetomidine Pharmacokinetics-pharmacodynamics in Mechanically Ventilated Children With Single-organ Respiratory Failure
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Respiratory Failure
Keywords: Patients with single-organ failure in need of mechanical ventilation
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
First posted: 2010-02-26
Enrollment: 1
Sex: ALL
Minimum age (years): 1
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: pharmacokinetic parameters of dexmedetomidine infusion in mechanically ventilated children with single-organ respiratory failure
timeFrame: 48 hours
measure: covariates contributing to a variability in exposure and response to dexmedetomidine
timeFrame: 48 hours
Secondary outcomes:
measure: preliminary knowledge on the level of sedation provided by dexmedetomidine
timeFrame: 48 hours
measure: preliminary knowledge of safety issues
timeFrame: 48 hours
measure: knowledge of the contribution of the CYP2A6 and UDP-glucuronosyltransferase genotype (covariate) to the variability in exposure and response to dexmedetomidine
timeFrame: 48 hours
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Ghent
country: Belgium
facility: University Hospital Ghent
Study officials:
affiliation: University Hospital, Ghent
name: Pieter De Cock, Pharm.D
role: PRINCIPAL_INVESTIGATOR
References: