Heart Ventricle, Hypoplastic Left Heart, Tetrology of Fallot
Conditions
Keywords
Precedex, Open Heart Surgery, Dexmedetomidine, Sedation
Brief summary
The purpose of this study is to determine what happens to dexmedetomidine in the body after it has been given to a newborn after heart surgery. We want to learn how long the drug stays in the body, how the drug is metabolized by the body, and how well the medicine works at a particular dose or amount.
Detailed description
This is a single center, dose escalation study of a single bolus dose of dexmedetomidine followed by a continuous infusion for up to 24 hours in neonates who are immediately post-op from cardiac surgery, and require tracheal intubation with mechanical ventilation in the post-op period. Pediatric populations may benefit from the favorable pharmacodynamic effects of this medication.
Interventions
DRUGDexmedetomidine
Dosage Level 1=0.25mcg/kg loading dose, 0.2 mcg/kg/hr infusion Dosage Level 1A= 0.35mcg/kg loading dose, 0.3 mcg/kg/hr infusion Dosage Level 2= 0.5mcg/kg loading dose, 0.4 mcg/kg/hr infusion
Sponsors
Athena Zuppa
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Hours to 30 Days
Healthy volunteers
No
Inclusion criteria
* Patients must be less than or equal to 1 month old. * Postconceptual age must be \> or equal to 37 weeks on the day of surgery. * Postoperative from cardiac surgery with tracheal intubation/mechanical ventilation in the immediate post-op period. * Planned tracheal extubation within 24 hrs post-op. * Adequate renal function (serum creatine \< or equal to 1.5mg/dL) * Adequate liver function (ALT \< or equal to 165 U/L) * Isolated heart surgery * Informed consent
Exclusion criteria
* Patients who have received another investigational drug since birth. * Patients receiving continuous infusions of muscle relaxants in the post-op setting. * Pateints who have a positive blood culture without a subsequent negative culture of other evidence of ongoing serious infection. * Patients who show signs and symptoms of elevated intracranial pressure. * Post-op hypotension defined by post conceptual age. * Pre-existing bradycardia defined by age * Heart block * Weight \< 2kg * Patients who, in the opinion of the investigator, are not appropriate candidates for an investigational drug study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK Profile of Dexmedetomidine | A sparse PK sampling method was utilized. Between 6-12 PK samples were drawn : After start of infusion (0.5, 4-6, 8 hours), immediately prior to end of infusion and following end of infusion (0.25, 0.5, 1, 2-4, 6-8, 10-12 & 18hrs) | This study measured the concentration of dex in the body and used those concentrations to determine how quickly the body metabolizes and eliminates dex(concentration-time or pharmacokinetic profile).The concentration of dex in the body is determined through serial blood sampling while administering dex and following discontinuation. |
Countries
United States
Participant flow
Recruitment details
All subjects were recruited from inpatient cardiac intensive care unit prior to open heart surgery.
Participants by arm
| Arm | Count |
|---|---|
| Dosing Cohorts Neonates will be administered a single bolus dose of dexmedetomidine followed by a continuous infuusion for up to 24 hours post cardiac surgery.
Dexmedetomidine : Dosage Level 1=0.25mcg/kg loading dose, 0.2 mcg/kg/hr infusion Dosage Level 1A= 0.35mcg/kg loading dose, 0.3 mcg/kg/hr infusion Dosage Level 2= 0.5mcg/kg loading dose, 0.4 mcg/kg/hr infusion | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Reoperation | 3 |
Baseline characteristics
| Characteristic | Dosing Cohorts |
|---|---|
| Age, Categorical <=18 years | 30 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / 30 |
| serious Total, serious adverse events | 2 / 30 |
Outcome results
Primary
PK Profile of Dexmedetomidine
This study measured the concentration of dex in the body and used those concentrations to determine how quickly the body metabolizes and eliminates dex(concentration-time or pharmacokinetic profile).The concentration of dex in the body is determined through serial blood sampling while administering dex and following discontinuation.
Time frame: A sparse PK sampling method was utilized. Between 6-12 PK samples were drawn : After start of infusion (0.5, 4-6, 8 hours), immediately prior to end of infusion and following end of infusion (0.25, 0.5, 1, 2-4, 6-8, 10-12 & 18hrs)
Population: Based on an estimated inter-subject variability of 50% for clearance, a sample size of 32 evaluable subjects will be sufficient to detect an 18% difference (alpha 0.05, power 0.9) in the clearance in this population (38 + 18 L/hr) versus that previously reported in the adult population (46 L/hr).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Neonates | PK Profile of Dexmedetomidine | 110 mL/min | Standard Error 6.24 |