Sedation
Conditions
Keywords
Initially intubated and mechanically ventilated neonates
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).
Interventions
DRUGMidazolam
Per package insert, N-PASS (Neonatal Pain, Agitation, and Sedation Scale) scores and investigator discretion
DRUGFentanyl/Morphine
Per package insert, N-PASS scores and investigator discretion.
DRUGDexmedetomidine
Sponsors
Hospira, now a wholly owned subsidiary of Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
28 Weeks to 44 Weeks
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Subjects Who Received Rescue Medication Midazolam for Sedation During Dexmedetomidine Infusion | During study drug administration (6 to 24 hours) |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Subjects Who Received Rescue Medication for Analgesia During Dexmedetomidine Infusion | 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) |
| 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 Midazolam 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 Fentanyl Given for Analgesia 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 |
Countries
Guatemala, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dexmedetomidine 0.05 mcg/kg Dexmedetomidine loading dose 0.05 mcg/kg; maintenance infusion: 0.05 mcg/kg/hr.
Midazolam: Per package insert, N-PASS scores and investigator discretion
Fentanyl: Per package insert, N-PASS scores and investigator discretion.
Dexmedetomidine | 14 |
| Dexmedetomidine 0.1 mcg/kg Dexmedetomidine loading dose: 0.1 mcg/kg; maintenance infusion 0.1 mcg/kg/hr.
Midazolam: Per package insert, N-PASS scores and investigator discretion
Fentanyl: Per package insert, N-PASS scores and investigator discretion.
Dexmedetomidine | 14 |
| Dexmedetomidine 0.2 mcg/kg Dexmedetomidine loading dose 0.2 mcg/kg; maintenance infusion 0.2 mcg/kg/hr.
Midazolam: Per package insert, N-PASS scores and investigator discretion
Fentanyl: Per package insert, N-PASS scores and investigator discretion.
Dexmedetomidine | 8 |
| Total | 36 |
Baseline characteristics
| Characteristic | Dexmedetomidine 0.05 mcg/kg | Dexmedetomidine 0.1 mcg/kg | Dexmedetomidine 0.2 mcg/kg | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 14 Participants | 14 Participants | 8 Participants | 36 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 1.637 weeks STANDARD_DEVIATION 1.829 | 1.098 weeks STANDARD_DEVIATION 1.0849 | 2.225 weeks STANDARD_DEVIATION 1.5779 | 1.558 weeks STANDARD_DEVIATION 1.5382 |
| Age, Customized = 28 weeks to < 36 weeks gestational age | 6 Participants | 6 Participants | 0 Participants | 12 Participants |
| Age, Customized >= 36 weeks to <= 44 weeks gestational age | 8 Participants | 8 Participants | 8 Participants | 24 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) White | 10 Participants | 10 Participants | 6 Participants | 26 Participants |
| Region of Enrollment United States | 14 participants | 14 participants | 8 participants | 36 participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 0 Participants | 12 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 8 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 14 | 9 / 14 | 6 / 8 |
| serious Total, serious adverse events | 0 / 14 | 1 / 14 | 0 / 8 |
Outcome results
Primary
Percentage of Subjects Who Received Rescue Medication Midazolam for Sedation During Dexmedetomidine Infusion
Time frame: During study drug administration (6 to 24 hours)
Population: Efficacy Evaluable Population: All subjects who received randomized Dexmedetomidine for at least 6 hours.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dexmedetomidine 0.05 mcg/kg | Percentage of Subjects Who Received Rescue Medication Midazolam for Sedation During Dexmedetomidine Infusion | 7.1 percentage of subjects |
| Dexmedetomidine 0.1 mcg/kg | Percentage of Subjects Who Received Rescue Medication Midazolam for Sedation During Dexmedetomidine Infusion | 7.1 percentage of subjects |
| Dexmedetomidine 0.2 mcg/kg | Percentage of Subjects Who Received Rescue Medication Midazolam for Sedation During Dexmedetomidine Infusion | 25 percentage of subjects |
Secondary
Percentage of Subjects Who Received Rescue Medication for Analgesia During Dexmedetomidine Infusion
Time frame: During Study drug administration (6 to 24 hours)
Population: Efficacy Evaluable Population: All subjects who received randomized Dexmedetomidine for at least 6 hours.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dexmedetomidine 0.05 mcg/kg | Percentage of Subjects Who Received Rescue Medication for Analgesia During Dexmedetomidine Infusion | 35.7 percentage of subjects |
| Dexmedetomidine 0.1 mcg/kg | Percentage of Subjects Who Received Rescue Medication for Analgesia During Dexmedetomidine Infusion | 35.7 percentage of subjects |
| Dexmedetomidine 0.2 mcg/kg | Percentage of Subjects Who Received Rescue Medication for Analgesia During Dexmedetomidine Infusion | 75 percentage of subjects |
Secondary
Time to Successful Extubation in DEX-exposed Subjects
Time frame: From start of DEX administration to extubation of each subject up to 7 days post-infusion
Population: Efficacy Evaluable Population: All subjects who received randomized Dexmedetomidine for at least 6 hours.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dexmedetomidine 0.05 mcg/kg | Time to Successful Extubation in DEX-exposed Subjects | 22.9 hour |
| Dexmedetomidine 0.1 mcg/kg | Time to Successful Extubation in DEX-exposed Subjects | 49.3 hour |
| Dexmedetomidine 0.2 mcg/kg | Time to Successful Extubation in DEX-exposed Subjects | 23.7 hour |
Secondary
Total Amount of Rescue Medication Fentanyl Given for Sedation During Dexmedetomidine Infusion (Among Who Used)
Time frame: During study drug administration (6 to 24 hours)
Population: All subjects who received fentanyl during Dexmedetomidine infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dexmedetomidine 0.05 mcg/kg | Total Amount of Rescue Medication Fentanyl Given for Sedation During Dexmedetomidine Infusion (Among Who Used) | 10.808 Microgram | Standard Deviation 7.1305 |
| Dexmedetomidine 0.1 mcg/kg | Total Amount of Rescue Medication Fentanyl Given for Sedation During Dexmedetomidine Infusion (Among Who Used) | 5.667 Microgram | Standard Deviation 3.5119 |
| Dexmedetomidine 0.2 mcg/kg | Total Amount of Rescue Medication Fentanyl Given for Sedation During Dexmedetomidine Infusion (Among Who Used) | 9.522 Microgram | Standard Deviation 7.5131 |
Secondary
Total Amount of Rescue Medication Midazolam Given for Sedation During Dexmedetomidine Infusion (Among Who Used)
Time frame: During Study drug administration (6 to 24 hours)
Population: All subjects who received midazolam during Dexmedetomidine infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dexmedetomidine 0.05 mcg/kg | Total Amount of Rescue Medication Midazolam Given for Sedation During Dexmedetomidine Infusion (Among Who Used) | .360 Milligram | — |
| Dexmedetomidine 0.1 mcg/kg | Total Amount of Rescue Medication Midazolam Given for Sedation During Dexmedetomidine Infusion (Among Who Used) | .500 Milligram | — |
| Dexmedetomidine 0.2 mcg/kg | Total Amount of Rescue Medication Midazolam Given for Sedation During Dexmedetomidine Infusion (Among Who Used) | 1.125 Milligram | Standard Deviation 1.4637 |
Secondary
Total Amount of Rescue Medication Morphine Given for Sedation During Dexmedetomidine Infusion (Among Who Used)
Time frame: During study drug administration (6 to 24 hours)
Population: All subjects who received morphine during Dexmedetomidine infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dexmedetomidine 0.1 mcg/kg | Total Amount of Rescue Medication Morphine Given for Sedation During Dexmedetomidine Infusion (Among Who Used) | 0.275 milligram | Standard Deviation 0.0354 |
| Dexmedetomidine 0.2 mcg/kg | Total Amount of Rescue Medication Morphine Given for Sedation During Dexmedetomidine Infusion (Among Who Used) | 0.400 milligram | Standard Deviation 0.1732 |
Secondary
Weight-adjusted Total Amount (Per kg) of Rescue Medication Fentanyl Given for Analgesia During Dexmedetomidine Infusion (Among Who Used)
Time frame: During study drug administration (6 to 24 hours)
Population: All subjects who received fentanyl during Dexmedetomidine infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dexmedetomidine 0.05 mcg/kg | Weight-adjusted Total Amount (Per kg) of Rescue Medication Fentanyl Given for Analgesia During Dexmedetomidine Infusion (Among Who Used) | 5.137 microgram/Kg | Standard Deviation 6.3696 |
| Dexmedetomidine 0.1 mcg/kg | Weight-adjusted Total Amount (Per kg) of Rescue Medication Fentanyl Given for Analgesia During Dexmedetomidine Infusion (Among Who Used) | 1.863 microgram/Kg | Standard Deviation 0.8761 |
| Dexmedetomidine 0.2 mcg/kg | Weight-adjusted Total Amount (Per kg) of Rescue Medication Fentanyl Given for Analgesia During Dexmedetomidine Infusion (Among Who Used) | 2.725 microgram/Kg | Standard Deviation 2.1383 |
Secondary
Weight-adjusted Total Amount (Per kg) of Rescue Medication Midazolam Given for Sedation During Dexmedetomidine Infusion (Among Who Used)
Time frame: During study drug administration (6 to 24 hours)
Population: All subjects who received midazolam during Dexmedetomidine infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dexmedetomidine 0.05 mcg/kg | Weight-adjusted Total Amount (Per kg) of Rescue Medication Midazolam Given for Sedation During Dexmedetomidine Infusion (Among Who Used) | 0.100 milligrams/Kg | — |
| Dexmedetomidine 0.1 mcg/kg | Weight-adjusted Total Amount (Per kg) of Rescue Medication Midazolam Given for Sedation During Dexmedetomidine Infusion (Among Who Used) | 0.152 milligrams/Kg | — |
| Dexmedetomidine 0.2 mcg/kg | Weight-adjusted Total Amount (Per kg) of Rescue Medication Midazolam Given for Sedation During Dexmedetomidine Infusion (Among Who Used) | 0.318 milligrams/Kg | Standard Deviation 0.4133 |
Secondary
Weight-adjusted Total Amount (Per kg) of Rescue Medication Morphine Given for Analgesia During Dexmedetomidine Infusion (Among Who Used)
Time frame: During study drug administration (6 to 24 hours)
Population: All subjects who received morphine during Dexmedetomidine infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dexmedetomidine 0.1 mcg/kg | Weight-adjusted Total Amount (Per kg) of Rescue Medication Morphine Given for Analgesia During Dexmedetomidine Infusion (Among Who Used) | 0.125 milligram/Kg | Standard Deviation 0.0348 |
| Dexmedetomidine 0.2 mcg/kg | Weight-adjusted Total Amount (Per kg) of Rescue Medication Morphine Given for Analgesia During Dexmedetomidine Infusion (Among Who Used) | 0.109 milligram/Kg | Standard Deviation 0.054 |