Anesthesia
Conditions
Brief summary
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.
Interventions
DRUGDexmedetomidine
DRUGMidazolam
DRUGFentanyl
DRUGMorphine
Sponsors
Hospira, now a wholly owned subsidiary of Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
28 Weeks to 36 Weeks
Healthy volunteers
No
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.
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 | The N-PASS score \>3 indicates adequately sedated and not manifesting signs of pain/agitation. |
| Time to Successful Extubation | From the start of study drug infusion to the study completion/withdrawal (Approximately 48 hours) | — |
Countries
United States
Participant flow
Recruitment details
Neonatal subjects enrolled from 3 centers in the United States
Participants by arm
| Arm | Count |
|---|---|
| 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) | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Dexmedetomidine |
|---|---|
| Age, Categorical <=18 years | 6 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous Age Continuous | 0.8 weeks STANDARD_DEVIATION 1.36 |
| Age, Continuous Age Continuous: units: Gestational Age | 32.5 weeks STANDARD_DEVIATION 2.74 |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Percent of Subjects Requiring Rescue Midazolam for Sedation
Time frame: 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).
Population: All Subjects who received study drug for at least 6 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dexmedetomidine | Percent of Subjects Requiring Rescue Midazolam for Sedation | 0 percentage of participants |
Secondary
Amount of Rescue Medication for Analgesia During DEX Infusion
Time frame: 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).
Population: Number of subject who received rescue medication for analgesia during DEX infusion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dexmedetomidine | Amount of Rescue Medication for Analgesia During DEX Infusion | 1 mcg/kg |
Secondary
Amount of Rescue Medication (Midazolam) for Sedation During Dexmedetomidine Infusion
Time frame: 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).
Population: No participants analyzed for this assessment since none required rescue Midazolam for sedation.
Secondary
Incidence of Rescue Medication (Fentanyl or Morphine) Use for Analgesia During DEX Infusion
Time frame: 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).
Population: All subjects who received DEX for at least 6 hours formed the Efficacy Evaluable Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dexmedetomidine | Incidence of Rescue Medication (Fentanyl or Morphine) Use for Analgesia During DEX Infusion | 1 participant |
Secondary
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.
Time frame: 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
Population: All subjects who received DEX for at least 6 hours formed the Efficacy Evaluable Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dexmedetomidine | Time Spent With a Total N-PASS Score >3 During DEX Infusion | 0.44 Hours | Standard Deviation 0.769 |
Secondary
Time to Successful Extubation
Time frame: From the start of study drug infusion to the study completion/withdrawal (Approximately 48 hours)
Population: Subjects who had successful extubation alone (n=5) were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dexmedetomidine | Time to Successful Extubation | 37.3 Hours |