Dexmedetomidine in Mechanically Ventilated Neonates With Single-Organ Respiratory Failure. (NEODEX)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by University Hospital, Ghent
Sponsor:
Collaborator:
Orion Corporation, Orion Pharma
Information provided by (Responsible Party):
University Hospital, Ghent
ClinicalTrials.gov Identifier:
NCT01266252
First received: December 22, 2010
Last updated: January 29, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Mechanically-ventilated Neonates With Single-organ Respiratory Failure.
Drug: Dexmedetomidine
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Dexmedetomidine Pharmacokinetics - Pharmacodynamics in Mechanically Ventilated Neonates With Single-organ Respiratory Failure (NEODEX).

Resource links provided by NLM:


Further study details as provided by University Hospital, Ghent:

Primary Outcome Measures:
  • pharmacokinetic parameters [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters of dexmedetomidine infusion in mechanically ventilated neonates with single-organ respiratory failure.

  • Covariates [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Covariates contributing to a variability in exposure and response to dexmedetomidine.


Secondary Outcome Measures:
  • level of analgosedation [ Time Frame: 72 hours ] [ Designated as safety issue: Yes ]
    Preliminary knowledge on the level of analgosedation provided by dexmedetomidine.

  • safety issues [ Time Frame: 72 hours ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 60
Study Start Date: February 2011
Estimated Study Completion Date: August 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dexmedetomidine Drug: Dexmedetomidine

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.


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.

  Eligibility

Ages Eligible for Study:   up to 1 Month
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01266252

Contacts
Contact: Pieter De Cock, Pharmacist Pieter.Decock@uzgent.be

Locations
Belgium
AZ Bruges Recruiting
Bruges, Belgium, 8000
Contact: Wim Decaluwe, MD       Wim.Decaluwe@azbrugge.be   
Principal Investigator: Wim Decaluwe, MD         
Ghent University Hospital Recruiting
Ghent, Belgium, 9000
Principal Investigator: Piet Vanhaesebrouck, MD, PhD         
UZ Leuven Recruiting
Leuven, Belgium
Contact: Karel Allegaert, MD, PhD         
Principal Investigator: Karel Allegaert, MD, PhD         
Sponsors and Collaborators
University Hospital, Ghent
Orion Corporation, Orion Pharma
Investigators
Principal Investigator: Piet Vanhaesebrouck, MD, PhD Ghent University Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: University Hospital, Ghent
ClinicalTrials.gov Identifier: NCT01266252     History of Changes
Other Study ID Numbers: EC/2010/786
Study First Received: December 22, 2010
Last Updated: January 29, 2013
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Belgium: Ethics Committee

Keywords provided by University Hospital, Ghent:
neonates
single organ respiratory failure

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

ClinicalTrials.gov processed this record on October 23, 2014