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

Dexmedetomidine Pharmacokinetics - Pharmacodynamics in Mechanically Ventilated Neonates With Single-organ Respiratory Failure (NEODEX).

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.

Study Overview

• Status: Completed
• Conditions: Mechanically-ventilated Neonates With Single-organ Respiratory Failure
• Intervention / Treatment: Drug: Dexmedetomidine

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.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Bruges, Belgium, 8000
    • AZ Bruges
  • Ghent, Belgium, 9000
    • Ghent University Hospital
  • Leuven, Belgium
    • UZ Leuven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 month (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pharmacokinetic parameters	Pharmacokinetic parameters of dexmedetomidine infusion in mechanically ventilated neonates with single-organ respiratory failure.	72 hours
Covariates	Covariates contributing to a variability in exposure and response to dexmedetomidine.	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
level of analgosedation	Preliminary knowledge on the level of analgosedation provided by dexmedetomidine.	72 hours
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.	72 hours
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.	72 hours

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Collaborators: Orion Corporation, Orion Pharma
• Investigators: Principal Investigator: Koenraad Smets, MD, PhD, University Hospital, Ghent

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2011
• Primary Completion (Actual): April 20, 2017
• Study Completion (Actual): April 10, 2018

Study Registration Dates

• First Submitted: December 22, 2010
• First Submitted That Met QC Criteria: December 22, 2010
• First Posted (Estimate): December 24, 2010

Study Record Updates

• Last Update Posted (Actual): March 19, 2019
• Last Update Submitted That Met QC Criteria: March 15, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: neonates; single organ respiratory failure
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: EC/2010/786