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

Primary Purpose

Respiratory Failure

Status

Terminated

Phase

Phase 3

Locations

Belgium

Study Type

Interventional

Intervention

dexmedetomidine

Vital signs

blood sampling

About this trial

This is an interventional treatment trial for Respiratory Failure focused on measuring Patients with single-organ failure in need of mechanical ventilation

Eligibility Criteria

1 Month - 15 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Cliniques Universitaires Saint-Luc
University Hospital Ghent

Outcomes

Primary Outcome Measures

pharmacokinetic parameters of dexmedetomidine infusion in mechanically ventilated children with single-organ respiratory failure

covariates contributing to a variability in exposure and response to dexmedetomidine

Secondary Outcome Measures

preliminary knowledge on the level of sedation provided by dexmedetomidine

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

knowledge of the contribution of the CYP2A6 and UDP-glucuronosyltransferase genotype (covariate) to the variability in exposure and response to dexmedetomidine

Full Information

NCT ID

NCT01076816

First Posted

February 25, 2010

Last Updated

October 3, 2011

Sponsor

University Hospital, Ghent

1. Study Identification

Unique Protocol Identification Number

NCT01076816

Brief Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2011

Overall Recruitment Status

Terminated

Why Stopped

Poor inclusion rate.

Study Start Date

December 2009 (undefined)

Primary Completion Date

February 2011 (Actual)

Study Completion Date

May 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Ghent

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Respiratory Failure

Keywords

Patients with single-organ failure in need of mechanical ventilation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

1 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

dexmedetomidine

Intervention Description

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.

Intervention Type

Procedure

Intervention Name(s)

Vital signs

Intervention Description

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.

Intervention Type

Procedure

Intervention Name(s)

blood sampling

Intervention Description

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.

Primary Outcome Measure Information:

Title

pharmacokinetic parameters of dexmedetomidine infusion in mechanically ventilated children with single-organ respiratory failure

Time Frame

48 hours

Title

covariates contributing to a variability in exposure and response to dexmedetomidine

Time Frame

48 hours

Secondary Outcome Measure Information:

Title

preliminary knowledge on the level of sedation provided by dexmedetomidine

Time Frame

48 hours

Title

preliminary knowledge of safety issues

Description

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

Time Frame

48 hours

Title

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

1 Month

Maximum Age & Unit of Time

15 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pieter De Cock, Pharm.D

Organizational Affiliation

University Hospital, Ghent

Official's Role

Principal Investigator

Facility Information:

Facility Name

Cliniques Universitaires Saint-Luc

City

Brussels

ZIP/Postal Code

1200

Country

Belgium

Facility Name

University Hospital Ghent

City

Ghent

Country

Belgium

12. IPD Sharing Statement

Links:

URL

http://www.uzgent.be

Description

website of University Hospital Ghent

Learn more about this trial

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

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