Hypoplastic Left Heart, Tetralogy of Fallot, Tricuspid Atresia
Conditions
Keywords
Postoperative from cardiac surgery, Dexmedetomidine
Brief summary
This study is being conducted to determine what dexmedetomidine does to the body and in turn, what how the body handles the medication. This medication, for the purpose of this trial, is used as a short-term sedative for infants who are immediately post-operative from cardiac surgery and have a breathing tube and are breathing with the assistance of a mechanical ventilator or breathing machine.
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 infants who are immediately post-operative from cardiac surgery and require tracheal intubation with mechanical ventilation in the post-operative period. Three bolus doses and infusion doses will be administered to a total of 36 evaluable patients.
Interventions
DRUGDexmedetomidine
Dosage levels: Dose Level 1: Loading dose 0.35mcg/kg and CIVI 0.25mcg/kg/hr Dose Level 2: Loading Dose of 0.7mcg/kg and CIVI 0.5mcg/kg/hr and Dose Level 3: Loading Dose 1 mcg/kg and CIVI 0.75 mcg/kg/hr.
Sponsors
Athena Zuppa
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 24 Months
Healthy volunteers
No
Inclusion criteria
* Patients must be greater or equal to one month or less than or equal to 24 months of age. * Post operative from cardiac surgery with tracheal intubation/mechanical ventilation in the immediate post-op period. * Planned tracheal extubation within 24 hours post-operatively. * Adequate renal function(1-12 months old creatinine less than or equal to 0.6mg/dL and \>12 months to 24 months creatinine \< or= to 1.0mg/dL) * Adequate liver function(Total bilirubin \< or= 1.5mg/dL and ALT 1-12 months \< or = to 165 U/L and \> 12 months to 24 months \< or = to 90 U/L) * Isolated heart surgery * Informed consent
Exclusion criteria
* Patients who have received another investigational drug within the past 30 days. * Receiving continuous infusions of muscle relaxants in the postoperative setting. * Patients whoo have a positive blood culture without a subsequent negative culture or other evidence of ongoing serious infection. * Patients, who, int he opinion of the investigator may not be able to comply with the safety monitoring requirements of the study. * Patients who show signs or symptoms of elevated intracranial pressure. * Post-operative hypotension based on age. * Preexisting bradycardia based on age. * Heart block * Weight \< 5kg * 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 | after start of infusion (0.5, 1, 2, 4-6 hours), immediately prior to end of infusion and following end of infusion (0.25, 0.5, 1, 2, 4, 8, 12, 15-18 hours) | 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. |
Participant flow
Recruitment details
Recruitment occurred in the CHOP cardiac center during preoperative evaluation.
Pre-assignment details
All patients were evaluated postoperative to establish appropriateness for inclusion in the study.
Participants by arm
| Arm | Count |
|---|---|
| Dexmedetomidine, Infants, Cardiac Surgery Pharmacologic study of dexmedetomidine in infants following cardiac surgery Dexmedetomidine was administered to all subjects as an intravenous loading dose over 10 minutes followed by a continuous infusion for up to 24 hours.
Cohort 1--0.35mcg/kg loading dose, 0.25mcg/kg/hr infusion Cohort 2--0.7 mcg/kg loading dose, 0.5 mcg/kg/hr infusion Cohort 3--1 mcg/kg loading dose, 0.75 mcg/kg/hr infusion | 56 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Exclusion criteria | 18 |
| Overall Study | IV malfunction | 1 |
| Overall Study | Postoperative bleeding | 1 |
Baseline characteristics
| Characteristic | Dexmedetomidine, Infants, Cardiac Surgery |
|---|---|
| Age, Categorical <=18 years | 56 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age Continuous | 0.74 years STANDARD_DEVIATION 0.42 |
| Region of Enrollment United States | 56 participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 56 |
| serious Total, serious adverse events | 3 / 56 |
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: after start of infusion (0.5, 1, 2, 4-6 hours), immediately prior to end of infusion and following end of infusion (0.25, 0.5, 1, 2, 4, 8, 12, 15-18 hours)
Population: Based on an estimated inter-subject variability of 50% for steady state concentration, a sample size of 36 evaluable subjects will be sufficient to detect a difference (alpha 0.05, power 0.8) for the area under the concentration-time curve (AUC) and steady state concentration (Css) between the three dosing groups.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dexmedetomidine, Infants, Cardiac Surgery | PK Profile of Dexmedetomidine | 28 mL/min/(kg^0.75) | Standard Error 0.08 |