Safety and Efficacy Study of Dexmedetomidine in Pediatrics Ages >= 28 Weeks to <= 44 Weeks Gestational Age

• Incidence of rescue medication for analgesia during study drug infusion [ Time Frame: 6 to 24 hours ] [ Designated as safety issue: Yes ]
• Amount of rescue medication for sedation during study drug infusion. [ Time Frame: 6 to 24 hours ] [ Designated as safety issue: Yes ]
• Change from baseline in vital signs, respiratory rate and oxygenation measures during study drug infusion [ Time Frame: 6 to 24 hours ] [ Designated as safety issue: Yes ]
• Time spent with an N-PASS score >3 during study drug administration [ Time Frame: 6 to 24 hours ] [ Designated as safety issue: Yes ]
• Time from study drug administration to extubation. [ Time Frame: 6 to 24 hours ] [ Designated as safety issue: Yes ]

The purpose of this study is to investigate the safety, efficacy and pharmacokinetics (PK) of dexmedetomidine (DEX) at 3 different dose levels in infants, ages ≥ 28 weeks to ≤ 44 weeks gestational age, administered as a loading dose followed by a continuous infusion for a minimum of 6 hours and up to 24 hours in the neonatal intensive unit care unit (NICU), cardiac intensive unit care unit (CICU), or pediatric intensive unit care unit (PICU).

• Drug: Midazolam
  Per package insert, N-PASS scores and investigator discretion
• Drug: Fentanyl
  Per package insert, N-PASSS scores and investigator discretion.
• Drug: Dexmedetomidine
  Other Name: Precedex

• Experimental: Dexmedetomidine 0.05 mcg/kg
  Dexmedetomidine loading dose 0.05 mcg/kg; maintenance infusion: 0.05 mcg/kg/hr.
  Interventions:

  • Drug: Midazolam
  • Drug: Fentanyl
  • Drug: Dexmedetomidine
• Experimental: Dexmedetomidine 0.1 mcg/kg
  Dexmedetomidine loading dose: 0.1 mcg/kg; maintenance infusion 0.1 mcg/kg/hr.
  Interventions:

  • Drug: Midazolam
  • Drug: Fentanyl
  • Drug: Dexmedetomidine
• Experimental: Dexmedetomidine 0.2 mcg/kg
  Dexmedetomidine loading dose 0.2 mcg/kg; maintenance infusion 0.2 mcg/kg/hr.
  Interventions:

  • Drug: Midazolam
  • Drug: Fentanyl
  • Drug: Dexmedetomidine

Inclusion Criteria:

• Initially intubated and mechanically ventilated pediatric subjects in an intensive care setting anticipated to require a minimum of 6 hours of continuous IV sedation.
• The ability to complete all PK sampling blood draws.

• Age: subjects must fit into 1 of the following age ranges at screening:

  • Preterm neonates ≥ 28 weeks through < 36 weeks, gestational age; this would constitute treatment Group I.
  • Term neonates born at ≥ 36 weeks through ≤ 44 weeks gestational age; this would constitute treatment Group II.
• Weight: subject's weight at the time of enrollment must be > 1000 g.
• Subject's parent(s) or legal guardian(s) has/have voluntarily signed and dated the informed consent document approved by the Institutional Review Board (IRB)/Independent Ethics Committee (IEC).

Exclusion Criteria:

• Neonate subjects with neurological conditions that prohibit an evaluation of sedation such as:

  • Diminished consciousness from increased intracranial pressure.
  • The presence of catastrophic brain injury or other severe mental disorders that would make responses to sedatives unpredictable and/or measurement of the N PASS unreliable.
  • Subjects with immobility from neuromuscular disease or continuous infusion of neuromuscular blocking (NMB) agents.
• Subjects with second degree or third degree heart block unless subject has a pacemaker or pacing wires are in situ.
• HR < 120 bpm prior to the initiation of study drug.
• Exposure to any investigational drug within 30 days prior to study drug administration.
• Previous exposure to DEX as part of an investigational study.
• Maternal history of poly-substance drug abuse, based upon the presence of 1) an abnormal urine drug screen for cocaine, opiates and/or benzodiazepines; or 2) Investigator's judgment.
• At the discretion of the Investigator, subjects in whom the risk of DEX treatment is expected to exceed its benefits.
• Subjects who have a known allergy or contraindication to fentanyl, morphine, MDZ, DEX, or other α-2 agonists.
• Requirement for medications other than DEX, MDZ, morphine, or fentanyl for sedation and pain control.
• Screening ALT levels > 115 U/L.