Clinical trial NCT01159262: Safety, Efficacy and Pharmacokinetic Study of Dexmedetomidine in Pediatrics Ages ≥28 Weeks to ≤44 Weeks Gestational Age
Official title: A Phase II/III, Open-Label, Multicenter, Safety, Efficacy and Pharmacokinetic Study of Dexmedetomidine in Neonates Ages ≥28 Weeks to ≤44 Weeks Gestational Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Sedation
Keywords: Initially intubated and mechanically ventilated neonates
Lead sponsor: Hospira, now a wholly owned subsidiary of Pfizer
Sponsor class: INDUSTRY
First posted: 2010-07-09
Enrollment: 36
Sex: ALL
Minimum age (years): 28
Maximum age (years): 44
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Subjects Who Received Rescue Medication Midazolam for Sedation During Dexmedetomidine Infusion
timeFrame: During study drug administration (6 to 24 hours)
Secondary outcomes:
measure: Percentage of Subjects Who Received Rescue Medication for Analgesia During Dexmedetomidine Infusion
timeFrame: During Study drug administration (6 to 24 hours)
measure: Total Amount of Rescue Medication Midazolam Given for Sedation During Dexmedetomidine Infusion (Among Who Used)
timeFrame: During Study drug administration (6 to 24 hours)
measure: Total Amount of Rescue Medication Fentanyl Given for Sedation During Dexmedetomidine Infusion (Among Who Used)
timeFrame: During study drug administration (6 to 24 hours)
measure: Total Amount of Rescue Medication Morphine Given for Sedation During Dexmedetomidine Infusion (Among Who Used)
timeFrame: During study drug administration (6 to 24 hours)
measure: Weight-adjusted Total Amount (Per kg) of Rescue Medication Midazolam Given for Sedation During Dexmedetomidine Infusion (Among Who Used)
timeFrame: During study drug administration (6 to 24 hours)
measure: Weight-adjusted Total Amount (Per kg) of Rescue Medication Fentanyl Given for Analgesia During Dexmedetomidine Infusion (Among Who Used)
timeFrame: During study drug administration (6 to 24 hours)
measure: Weight-adjusted Total Amount (Per kg) of Rescue Medication Morphine Given for Analgesia During Dexmedetomidine Infusion (Among Who Used)
timeFrame: During study drug administration (6 to 24 hours)
measure: Time to Successful Extubation in DEX-exposed Subjects
timeFrame: From start of DEX administration to extubation of each subject up to 7 days post-infusion
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Long Beach
country: United States
facility: Miller Children's Hospital
state: California
city: Los Angeles
country: United States
facility: Childrens Hospital Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California San Francisco, Department of Pediatrics, Division of Neonatology
state: California
city: Stanford
country: United States
facility: Dept. of Anesthesia, SUMC
state: California
city: Miami
country: United States
facility: University of Miami - Miller School of Medicine, Department of Anesthesiology
state: Florida
city: Augusta
country: United States
facility: Georgia Health Sciences University
state: Georgia
city: Honolulu
country: United States
facility: Kapiolani Medical Center for Women and Children
state: Hawaii
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Wichita
country: United States
state: Kansas
city: Louisville
country: United States
facility: Kosair Charities Pediatric Clinical Research Unit, University of Louisville
state: Kentucky
city: Durham
country: United States
facility: Duke University Medical Center, Department of Anesthesiology
state: North Carolina
city: Akron
country: United States
facility: Akron Children's Hospital Medical Center
state: Ohio
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
city: Greenville
country: United States
state: South Carolina
city: Morgantown
country: United States
facility: West Virginia University School of Medicine
state: West Virginia
city: Zona 11 Guatemala
country: Guatemala
Study officials:
References:
citation: 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.