Safety, Efficacy and Pharmacokinetic Study of Dexmedetomidine in Pediatrics Ages ≥28 Weeks to ≤44 Weeks Gestational Age

A Phase II/III, Open-Label, Multicenter, Safety, Efficacy and Pharmacokinetic Study of Dexmedetomidine in Neonates Ages ≥28 Weeks to ≤44 Weeks Gestational Age

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 care unit (NICU), cardiac intensive care unit (CICU), or pediatric intensive care unit (PICU).

Study Overview

• Status: Completed
• Conditions: Sedation
• Intervention / Treatment: Drug: Dexmedetomidine; Drug: Midazolam; Drug: Fentanyl/Morphine

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Guatemala
  • Zona 11 Guatemala, Guatemala, C.P. 01011
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
  • California
    • Long Beach, California, United States, 90806
      • Miller Children's Hospital
    • Los Angeles, California, United States, 90027
      • Childrens Hospital Los Angeles
    • San Francisco, California, United States, 94143-0734
      • University of California San Francisco, Department of Pediatrics, Division of Neonatology
    • Stanford, California, United States, 94305
      • Dept. of Anesthesia, SUMC
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami - Miller School of Medicine, Department of Anesthesiology
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Health Sciences University
  • Hawaii
    • Honolulu, Hawaii, United States, 96826
      • Kapiolani Medical Center for Women and Children
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Kansas
    • Wichita, Kansas, United States, 67214
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Kosair Charities Pediatric Clinical Research Unit, University of Louisville
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center, Department of Anesthesiology
  • Ohio
    • Akron, Ohio, United States, 44308
      • Akron Children's Hospital Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina (MUSC)
    • Greenville, South Carolina, United States, 29605
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

3. 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.
4. Weight: subject's weight at the time of enrollment must be >1000 g.
5. 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:

1. 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.
2. Subjects with second degree or third degree heart block unless subject has a pacemaker or pacing wires are in situ.
3. Heart rate <120 bpm prior to the initiation of study drug.
4. Exposure to any investigational drug within 30 days prior to study drug administration.
5. Previous exposure to Dexmedetomidine (DEX) as part of an investigational study.
6. 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.
7. At the discretion of the Investigator, subjects in whom the risk of DEX treatment is expected to exceed its benefits.
8. Subjects who have a known allergy or contraindication to fentanyl, morphine, Midazolam, DEX, or other α-2 agonists.
9. Requirement for medications other than DEX, Midazolam, morphine, or fentanyl for sedation and pain control.
10. Screening alanine aminotransferase (ALT) levels >115 U/L.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dexmedetomidine 0.05 mcg/kg; Dexmedetomidine loading dose 0.05 mcg/kg; maintenance infusion: 0.05 mcg/kg/hr.	Drug: Dexmedetomidine; Other Names: Precedex; Drug: Midazolam; Per package insert, N-PASS (Neonatal Pain, Agitation, and Sedation Scale) scores and investigator discretion; Drug: Fentanyl/Morphine; Per package insert, N-PASS scores and investigator discretion.
Experimental: Dexmedetomidine 0.1 mcg/kg; Dexmedetomidine loading dose: 0.1 mcg/kg; maintenance infusion 0.1 mcg/kg/hr.	Drug: Dexmedetomidine; Other Names: Precedex; Drug: Midazolam; Per package insert, N-PASS (Neonatal Pain, Agitation, and Sedation Scale) scores and investigator discretion; Drug: Fentanyl/Morphine; Per package insert, N-PASS scores and investigator discretion.
Experimental: Dexmedetomidine 0.2 mcg/kg; Dexmedetomidine loading dose 0.2 mcg/kg; maintenance infusion 0.2 mcg/kg/hr.	Drug: Dexmedetomidine; Other Names: Precedex; Drug: Midazolam; Per package insert, N-PASS (Neonatal Pain, Agitation, and Sedation Scale) scores and investigator discretion; Drug: Fentanyl/Morphine; Per package insert, N-PASS scores and investigator discretion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Subjects Who Received Rescue Medication Midazolam for Sedation During Dexmedetomidine Infusion	During study drug administration (6 to 24 hours)

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of Subjects Who Received Rescue Medication for Analgesia During Dexmedetomidine Infusion	During Study drug administration (6 to 24 hours)
Total Amount of Rescue Medication Midazolam Given for Sedation During Dexmedetomidine Infusion (Among Who Used)	During Study drug administration (6 to 24 hours)
Total Amount of Rescue Medication Fentanyl Given for Sedation During Dexmedetomidine Infusion (Among Who Used)	During study drug administration (6 to 24 hours)
Total Amount of Rescue Medication Morphine Given for Sedation During Dexmedetomidine Infusion (Among Who Used)	During study drug administration (6 to 24 hours)
Weight-adjusted Total Amount (Per kg) of Rescue Medication Midazolam Given for Sedation During Dexmedetomidine Infusion (Among Who Used)	During study drug administration (6 to 24 hours)
Weight-adjusted Total Amount (Per kg) of Rescue Medication Fentanyl Given for Analgesia During Dexmedetomidine Infusion (Among Who Used)	During study drug administration (6 to 24 hours)
Weight-adjusted Total Amount (Per kg) of Rescue Medication Morphine Given for Analgesia During Dexmedetomidine Infusion (Among Who Used)	During study drug administration (6 to 24 hours)
Time to Successful Extubation in DEX-exposed Subjects	From start of DEX administration to extubation of each subject up to 7 days post-infusion

Collaborators and Investigators

• Sponsor: Hospira, now a wholly owned subsidiary of Pfizer

Publications and helpful links

General Publications

• Chrysostomou C, Schulman SR, Herrera Castellanos M, Cofer BE, Mitra S, da Rocha MG, Wisemandle WA, Gramlich L. A phase II/III, multicenter, safety, efficacy, and pharmacokinetic study of dexmedetomidine in preterm and term neonates. J Pediatr. 2014 Feb;164(2):276-82.e1-3. doi: 10.1016/j.jpeds.2013.10.002. Epub 2013 Nov 14.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: June 30, 2010
• First Submitted That Met QC Criteria: July 8, 2010
• First Posted (Estimate): July 9, 2010

Study Record Updates

• Last Update Posted (Estimate): August 13, 2015
• Last Update Submitted That Met QC Criteria: July 23, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Initially intubated and mechanically ventilated neonates
• Additional Relevant MeSH Terms: 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; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Analgesics, Opioid; Narcotics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Fentanyl; Midazolam; Dexmedetomidine; Morphine
• Other Study ID Numbers: DEX-09-08