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

Study Overview
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Brief Summary
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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.

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

Conditions
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Anesthesia

Intervention / Treatment
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* Drug: Dexmedetomidine
* Drug: Midazolam
* Drug: Fentanyl
* Drug: Morphine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Initially intubated and mechanically ventilated pediatric subjects in an intensive care setting anticipated to require at least 6 hours of continuous IV sedation. 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. 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. 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. HR < 120 bpm prior to the initiation of DEX. Exposure to any investigational drug within 30 days prior to DEX administration. Previous exposure to DEX as part of an investigational study. 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. 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.

Ages Eligible for Study
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Minimum Age: 28 Weeks
Maximum Age: 36 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dexmedetomidine<br>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: Dexmedetomidine<br> <br> Drug: Midazolam<br> <br> Drug: Fentanyl<br> <br> Drug: Morphine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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) |