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

This study has been terminated.
(Poor inclusion rate.)
Sponsor:
Information provided by (Responsible Party):
University Hospital, Ghent
ClinicalTrials.gov Identifier:
NCT01076816
First received: February 25, 2010
Last updated: October 3, 2011
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
Respiratory Failure
Drug: dexmedetomidine
Procedure: Vital signs
Procedure: blood sampling
Phase 3

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

Resource links provided by NLM:


Further study details as provided by University Hospital, Ghent:

Primary Outcome Measures:
  • pharmacokinetic parameters of dexmedetomidine infusion in mechanically ventilated children with single-organ respiratory failure [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  • covariates contributing to a variability in exposure and response to dexmedetomidine [ Time Frame: 48 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • preliminary knowledge on the level of sedation provided by dexmedetomidine [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  • preliminary knowledge of safety issues [ Time Frame: 48 hours ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 48 hours ] [ Designated as safety issue: No ]

Enrollment: 1
Study Start Date: December 2009
Study Completion Date: May 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    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.
    Procedure: 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.
  Eligibility

Ages Eligible for Study:   1 Month to 15 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01076816

Locations
Belgium
Cliniques Universitaires Saint-Luc
Brussels, Belgium, 1200
University Hospital Ghent
Ghent, Belgium
Sponsors and Collaborators
University Hospital, Ghent
Investigators
Principal Investigator: Pieter De Cock, Pharm.D University Hospital, Ghent
  More Information

Additional Information:
No publications provided

Responsible Party: University Hospital, Ghent
ClinicalTrials.gov Identifier: NCT01076816     History of Changes
Other Study ID Numbers: 2009/518
Study First Received: February 25, 2010
Last Updated: October 3, 2011
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Belgium: Ethics Committee

Keywords provided by University Hospital, Ghent:
Patients with single-organ failure in need of mechanical ventilation

Additional relevant MeSH terms:
Respiratory Insufficiency
Respiration Disorders
Respiratory Tract Diseases
Dexmedetomidine
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 31, 2014