Dexmedetomidine in Mechanically Ventilated Neonates With Single-Organ Respiratory Failure. (NEODEX)
Primary Purpose
Mechanically-ventilated Neonates With Single-organ Respiratory Failure
Status
Completed
Phase
Phase 3
Locations
Belgium
Study Type
Interventional
Intervention
Dexmedetomidine
Sponsored by
About this trial
This is an interventional treatment trial for Mechanically-ventilated Neonates With Single-organ Respiratory Failure focused on measuring neonates, single organ respiratory failure
Eligibility Criteria
Inclusion Criteria:
patient age less than 1 month (Male/Female) (step-down strategy for age)
- first included patients (n=30): postmenstrual age >= 34 weeks (near-term neonates)
- following included patients (n=30) : postmenstrual age >= 25 weeks and < 34 weeks (preterm neonates)
- patients with single-organ respiratory failure in need for analgosedation (guidance : Comfort neo score >14 or Numeric Rating Scale (NRS) score Pain (P)/Comfort (C)>4)
- patients admitted to the neonatal intensive care unit
- expected to require at least 20 hours of mechanical ventilation
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 <72 hours
- patients with a known allergy to fentanyl
- congenital or acquired heart block (grade 3)
- sustained bradycardia
- haemodynamically unstable patients (definition : Mean Arterial Pressure (MAP) lower than : postmenstrual age (in weeks) - 5 millimeter Hg, eventually under dopamine infusion max. 16 mcg/kilogram/minute and/or dobutamine infusion maximal 16 mcg/kilogram/minute)
- patients with significant renal insufficiency (creatinine plasma level >1.5 milligram/deciliter)
- patients with significant hepatic insufficiency (as estimated by local investigators)
- previous treatment with α2-adrenoreceptor agonist clonidine within 14 days
- absence of parental consent
Sites / Locations
- AZ Bruges
- Ghent University Hospital
- UZ Leuven
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Dexmedetomidine
Arm Description
Outcomes
Primary Outcome Measures
pharmacokinetic parameters
Pharmacokinetic parameters of dexmedetomidine infusion in mechanically ventilated neonates with single-organ respiratory failure.
Covariates
Covariates contributing to a variability in exposure and response to dexmedetomidine.
Secondary Outcome Measures
level of analgosedation
Preliminary knowledge on the level of analgosedation provided by dexmedetomidine.
safety issues
Preliminary knowledge of safety issues concerning 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.
variability due to the Cytochrome P450 2A6 (CYP2A6) and Uridine diphosphate (UDP)-glucuronosyltransferase genotype
Knowledge of the contribution of the Cytochrome P450 2A6 (CYP2A6) and Uridine diphosphate (UDP)-glucuronosyltransferase genotype (covariate) to the variability in exposure and response to dexmedetomidine.
Full Information
NCT ID
NCT01266252
First Posted
December 22, 2010
Last Updated
March 15, 2019
Sponsor
University Hospital, Ghent
Collaborators
Orion Corporation, Orion Pharma
1. Study Identification
Unique Protocol Identification Number
NCT01266252
Brief Title
Dexmedetomidine in Mechanically Ventilated Neonates With Single-Organ Respiratory Failure.
Acronym
NEODEX
Official Title
Dexmedetomidine Pharmacokinetics - Pharmacodynamics in Mechanically Ventilated Neonates With Single-organ Respiratory Failure (NEODEX).
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
July 28, 2011 (Actual)
Primary Completion Date
April 20, 2017 (Actual)
Study Completion Date
April 10, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Ghent
Collaborators
Orion Corporation, Orion Pharma
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Clinical experience with dexmedetomidine in the paediatric population is limited. Critical illness can affect drug pharmacokinetics and -dynamics; the investigators cannot simply extrapolate adult data for use in children but the investigators are in need of data on pharmacokinetics and pharmacodynamics in every paediatric subpopulation.
Detailed Description
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, the investigators cannot simply extrapolate adult data for use in children but the investigators 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
Mechanically-ventilated Neonates With Single-organ Respiratory Failure
Keywords
neonates, single organ respiratory failure
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dexmedetomidine
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Dexmedetomidine
Intervention Description
Dexmedetomidine will be given maximal 72 hours. 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-painful patient (assessed by regular Comfort-neo and Numeric Rating Scale scoring). In case of oversedation or adverse drug events (hypotension, bradycardia), a downtitration (or stop) of the dexmedetomidine infusion is needed.
Primary Outcome Measure Information:
Title
pharmacokinetic parameters
Description
Pharmacokinetic parameters of dexmedetomidine infusion in mechanically ventilated neonates with single-organ respiratory failure.
Time Frame
72 hours
Title
Covariates
Description
Covariates contributing to a variability in exposure and response to dexmedetomidine.
Time Frame
72 hours
Secondary Outcome Measure Information:
Title
level of analgosedation
Description
Preliminary knowledge on the level of analgosedation provided by dexmedetomidine.
Time Frame
72 hours
Title
safety issues
Description
Preliminary knowledge of safety issues concerning 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
72 hours
Title
variability due to the Cytochrome P450 2A6 (CYP2A6) and Uridine diphosphate (UDP)-glucuronosyltransferase genotype
Description
Knowledge of the contribution of the Cytochrome P450 2A6 (CYP2A6) and Uridine diphosphate (UDP)-glucuronosyltransferase genotype (covariate) to the variability in exposure and response to dexmedetomidine.
Time Frame
72 hours
10. Eligibility
Sex
All
Maximum Age & Unit of Time
1 Month
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
patient age less than 1 month (Male/Female) (step-down strategy for age)
first included patients (n=30): postmenstrual age >= 34 weeks (near-term neonates)
following included patients (n=30) : postmenstrual age >= 25 weeks and < 34 weeks (preterm neonates)
patients with single-organ respiratory failure in need for analgosedation (guidance : Comfort neo score >14 or Numeric Rating Scale (NRS) score Pain (P)/Comfort (C)>4)
patients admitted to the neonatal intensive care unit
expected to require at least 20 hours of mechanical ventilation
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 <72 hours
patients with a known allergy to fentanyl
congenital or acquired heart block (grade 3)
sustained bradycardia
haemodynamically unstable patients (definition : Mean Arterial Pressure (MAP) lower than : postmenstrual age (in weeks) - 5 millimeter Hg, eventually under dopamine infusion max. 16 mcg/kilogram/minute and/or dobutamine infusion maximal 16 mcg/kilogram/minute)
patients with significant renal insufficiency (creatinine plasma level >1.5 milligram/deciliter)
patients with significant hepatic insufficiency (as estimated by local investigators)
previous treatment with α2-adrenoreceptor agonist clonidine within 14 days
absence of parental consent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Koenraad Smets, MD, PhD
Organizational Affiliation
University Hospital, Ghent
Official's Role
Principal Investigator
Facility Information:
Facility Name
AZ Bruges
City
Bruges
ZIP/Postal Code
8000
Country
Belgium
Facility Name
Ghent University Hospital
City
Ghent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
UZ Leuven
City
Leuven
Country
Belgium
12. IPD Sharing Statement
Links:
URL
http://www.uzgent.be
Description
Related Info
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Dexmedetomidine in Mechanically Ventilated Neonates With Single-Organ Respiratory Failure.
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