Open-Label, Safety, and Efficacy Study of Dexmedetomidine in Preterm Subjects Ages ≥28 Weeks to <36 Weeks Gestational Age

A Phase II/III, Open-Label, Multicenter, Safety, and Efficacy Study of Dexmedetomidine in Preterm Subjects Ages ≥28 Weeks to <36 Weeks Gestational Age

The primary objective of this study is to characterize the safety, and efficacy of Dexmedetomidine (DEX) administered as an intravenous (IV) loading dose followed by a continuous IV infusion in preterm subjects, ages ≥ 28 weeks through < 36 weeks gestational age.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Louisville, Kentucky, United States, 40202
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
  • South Carolina
    • Greenville, South Carolina, United States, 29605
  • West Virginia
    • Morgantown, West Virginia, United States, 26506

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 8 months (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 at least 6 hours of continuous IV sedation.

2. Age: subjects must fit the following age range at screening:

   Preterm subjects ≥28 weeks through <36 weeks, gestational age;

   Note: Gestational age (in weeks) will be calculated as follows: the time elapsed between the first day of the last menstrual period and the day of enrollment.

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

   Note: If subject's status-post Cardio Pulmonary Bypass (CPB) was managed without pacing wires in situ, the subject must not be suspected to be in second degree or third degree heart block at the time of DEX administration.

3. HR < 120 bpm prior to the initiation of DEX.
4. Exposure to any investigational drug within 30 days prior to DEX administration.
5. Previous exposure to DEX as part of an investigational study.
6. In subjects that are ex-utero for less than 72 hours, a maternal history of poly-substance drug abuse, based upon the Investigator's clinical 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, MDZ, DEX, or other α-2 agonists.
9. Requirement for medications other than DEX, MDZ, morphine, or fentanyl for sedation and pain control.
10. Screening ALT levels >115 U/L.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dexmedetomidine; Dexmedetomidine Load 0.2 mcg/kg over 10 or 20 min Dexmedetomidine Maintenance 0.2 mcg/kg/hr (at least 6 and up to 24 hours)	Drug: Morphine; Drug: Fentanyl; Drug: Dexmedetomidine; Drug: Midazolam

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent of Subjects Requiring Rescue Midazolam for Sedation	During the study drug administration (ie., loading dose 10 or 20 minutes and maintenance infusion minimum of 6 hours up to 24 hours) and during the post drug administration (up to 24 hours).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Rescue Medication (Fentanyl or Morphine) Use for Analgesia During DEX Infusion		During the study drug administration (ie., loading dose 10 or 20 minutes and maintenance infusion minimum of 6 hours up to 24 hours) and during the post drug administration (up to 24 hours).
Amount of Rescue Medication (Midazolam) for Sedation During Dexmedetomidine Infusion		During the study drug administration (ie., loading dose 10 or 20 minutes and maintenance infusion minimum of 6 hours up to 24 hours) and during the post drug administration (up to 24 hours).
Amount of Rescue Medication for Analgesia During DEX Infusion		During the study drug administration (ie., loading dose 10 or 20 minutes and maintenance infusion minimum of 6 hours up to 24 hours) and during the post drug administration (up to 24 hours).
Time Spent With a Total N-PASS Score >3 During DEX Infusion	The N-PASS score >3 indicates adequately sedated and not manifesting signs of pain/agitation.	Predose, loading dose (LD) 5 & 10mins/if LD is 20mins (5, 10, 15 & 20mins); maintenance infusion: 0 min, every 15mins (1st hr); every 30mins (2hrs), then hourly; within 5mins of DEX discontinuation; 5mins pre and post rescue medication
Time to Successful Extubation		From the start of study drug infusion to the study completion/withdrawal (Approximately 48 hours)

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: March 1, 2012
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: January 5, 2012
• First Submitted That Met QC Criteria: January 11, 2012
• First Posted (Estimate): January 12, 2012

Study Record Updates

• Last Update Posted (Actual): August 23, 2017
• Last Update Submitted That Met QC Criteria: August 10, 2017
• Last Verified: September 1, 2015

More Information

Terms related to this study

• 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-11-06