Study Evaluating Safety and Efficacy of Dexmedetomidine (DEX) in Intubated and Mechanically Ventilated Pediatric Intensive Care Unit (PICU) Subjects
Condition: Sedation
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to evaluate the safety and efficacy of dexmedetomidine (DEX) in
      intubated and mechanically ventilated pediatric intensive care unit (PICU) subjects. The key
      study objectives are:

        -  To characterize the loading and maintenance dosing of DEX by age group and overall
           medical condition of pediatric subjects

        -  To evaluate the safety and efficacy of loading and maintenance infusions for sedation in
           initially intubated and mechanically ventilated PICU subjects

        -  To explore the exposure-response relationship between dose of DEX and clinical measures
           of sedation and safety
    

Detailed description: 
      An estimated 175 subjects will be enrolled at approximately 40 investigative sites. Subjects
      will be divided into two treatment groups to receive either high dose or low dose
      Dexmedetomidine (DEX). The loading and maintenance doses in both groups will be stratified
      according to the presence or absence of cardiopulmonary bypass. The level of sedation will be
      assessed using the University of Michigan Sedation Scale (UMSS). Score 0 (awake/alert); Score
      1 (sleepy/responds appropriately); Score 2 (somnolent/arouses to light stimuli); Score 3
      (deep sleep/arouses to deeper); Score 4 (unarousable to stimuli).

      Based on these scores and clinical judgment, additional sedation with intravenous midazolam
      will be administered according to the label. The UMSS scores must be documented before the
      administration of every midazolam (MDZ) dose and within five minutes after each dose of MDZ.
      Fentanyl or morphine may be administered to treat pain. Subjects may be extubated after
      beginning of study drug but are not required to be as part of the study.

      The efficacy and safety parameters that will be monitored include sedation levels, heart
      rate, blood pressure and ventilation indicators. Once subjects have met site-specified
      respiratory criteria, they will undergo tracheal extubation. The dexmedetomidine infusion may
      be continued during and after extubation if further sedation is required post-extubation. The
      continuous infusion of dexmedetomidine must be administered for a minimum of 6 hours and a
      maximum of 24 hours. Sedation levels, heart rate, blood pressure, respiratory rate,
      ventilator settings, SpO2 and if available transcutaneous carbon dioxide (TcCO2) and/or
      arterial blood gases (ABG) will be monitored and recorded in the peri-extubation period.
    

Intervention name(s): Dexmedetomidine; Midazolam; Fentanyl; Morphine
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Study drug titrated up or down to maintain target UMSS range.; Rescue medication for sedation according to UMSS scores; Rescue medication for pain based on UMSS scores; Rescue medication for pain based on UMSS scores.
Intervention MeSH terms: Midazolam; Fentanyl; Dexmedetomidine; Morphine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Intubated and mechanically ventilated PICU subjects