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

Phase 2

Completed

• Conditions: Sedation
• Interventions: Drug: Midazolam; Drug: Fentanyl/Morphine; Drug: Dexmedetomidine

• Registration Number: NCT01159262
• Lead Sponsor: Hospira, now a wholly owned subsidiary of Pfizer

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-06-30
• Study Start: 2010-07
• Study First Submitted QC: 2010-07-08
• Study First Posted: 2010-07-09
• Primary Completion: 2011-08
• Study Completion: 2011-08
• Disposition First Submitted: 2012-09-12
• Disposition First Submitted QC: 2012-09-12
• Disposition First Posted: 2012-09-14
• Results First Submitted: 2014-01-24
• Results First Submitted QC: 2014-12-05
• Results First Posted: 2014-12-12
• Status Verified: 2015-07
• Last Update Submitted: 2015-07-23
• Last Update Posted: 2015-08-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dexmedetomidine 0.05 mcg/kg	Fentanyl/Morphine	Dexmedetomidine loading dose 0.05 mcg/kg; maintenance infusion: 0.05 mcg/kg/hr.
Dexmedetomidine 0.1 mcg/kg	Fentanyl/Morphine	Dexmedetomidine loading dose: 0.1 mcg/kg; maintenance infusion 0.1 mcg/kg/hr.
Dexmedetomidine 0.2 mcg/kg	Fentanyl/Morphine	Dexmedetomidine loading dose 0.2 mcg/kg; maintenance infusion 0.2 mcg/kg/hr.
Dexmedetomidine 0.05 mcg/kg	Midazolam	Dexmedetomidine loading dose 0.05 mcg/kg; maintenance infusion: 0.05 mcg/kg/hr.
Dexmedetomidine 0.1 mcg/kg	Midazolam	Dexmedetomidine loading dose: 0.1 mcg/kg; maintenance infusion 0.1 mcg/kg/hr.
Dexmedetomidine 0.05 mcg/kg	Dexmedetomidine	Dexmedetomidine loading dose 0.05 mcg/kg; maintenance infusion: 0.05 mcg/kg/hr.
Dexmedetomidine 0.1 mcg/kg	Dexmedetomidine	Dexmedetomidine loading dose: 0.1 mcg/kg; maintenance infusion 0.1 mcg/kg/hr.
Dexmedetomidine 0.2 mcg/kg	Dexmedetomidine	Dexmedetomidine loading dose 0.2 mcg/kg; maintenance infusion 0.2 mcg/kg/hr.
Dexmedetomidine 0.2 mcg/kg	Midazolam	Dexmedetomidine loading dose 0.2 mcg/kg; maintenance infusion 0.2 mcg/kg/hr.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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 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
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)
Percentage of Subjects Who Received Rescue Medication for Analgesia During Dexmedetomidine Infusion	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)
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)

Trial Locations

Locations (15)

Childrens Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

Georgia Health Sciences University; 🇺🇸 Augusta, Georgia, United States

Loyola University Medical Center; 🇺🇸 Maywood, Illinois, United States

University of Miami - Miller School of Medicine, Department of Anesthesiology; 🇺🇸 Miami, Florida, United States

Miller Children's Hospital; 🇺🇸 Long Beach, California, United States

Dept. of Anesthesia, SUMC; 🇺🇸 Stanford, California, United States

Arkansas Children's Hospital; 🇺🇸 Little Rock, Arkansas, United States

Kapiolani Medical Center for Women and Children; 🇺🇸 Honolulu, Hawaii, United States

Duke University Medical Center, Department of Anesthesiology; 🇺🇸 Durham, North Carolina, United States

Akron Children's Hospital Medical Center; 🇺🇸 Akron, Ohio, United States

Children's Hospital of Pittsburgh of UPMC; 🇺🇸 Pittsburgh, Pennsylvania, United States

West Virginia University School of Medicine; 🇺🇸 Morgantown, West Virginia, United States

University of California San Francisco, Department of Pediatrics, Division of Neonatology; 🇺🇸 San Francisco, California, United States

Kosair Charities Pediatric Clinical Research Unit, University of Louisville; 🇺🇸 Louisville, Kentucky, United States

Medical University of South Carolina (MUSC); 🇺🇸 Charleston, South Carolina, United States