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

Respiratory Failure Clinical Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01076816
• Other study ID #: 2009/518
• Status: Terminated
• Phase: Phase 3
• First received: February 25, 2010
• Last updated: October 3, 2011
• Start date: December 2009
• Est. completion date: May 2011

Study information

• Verified date: October 2011
• Source: University Hospital, Ghent
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsBelgium: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: May 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Month to 15 Years

Eligibility

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 a2-adrenoreceptor agonist clonidine within 14 days

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Respiratory Failure
• Respiratory Insufficiency

Intervention

Drug:
• dexmedetomidine
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.

Procedure:
• Vital signs
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
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.

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	University Hospital Ghent	Ghent

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Ghent

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	pharmacokinetic parameters of dexmedetomidine infusion in mechanically ventilated children with single-organ respiratory failure		48 hours	No
Primary	covariates contributing to a variability in exposure and response to dexmedetomidine		48 hours	No
Secondary	preliminary knowledge on the level of sedation provided by dexmedetomidine		48 hours	No
Secondary	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	Yes
Secondary	knowledge of the contribution of the CYP2A6 and UDP-glucuronosyltransferase genotype (covariate) to the variability in exposure and response to dexmedetomidine		48 hours	No

External Links

•   website of University Hospital Ghent