A Phase I Study of Dexmedetomidine Bolus and Infusion in Corrective Infant Cardiac Surgery: Safety and Pharmacokinetics

Study Overview
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Brief Summary
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The purpose of this Phase I study is to determine the safety of a drug called dexmedetomidine (DEX) as part of a balanced general anesthetic and sedative strategy for neonates and infants undergoing corrective cardiac surgery that requires the use of cardiopulmonary bypass for congenital cardiac problems. This study will also design and validate a dosing schema for the use of DEX as described above.

Official Title
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A Phase I Study of Dexmedetomidine Bolus and Infusion in Corrective Infant Cardiac Surgery: Safety and Pharmacokinetics

Conditions
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Transposition of the Great Arteries, Tetralogy of Fallot, Ventricular Septal Defect

Intervention / Treatment
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* Drug: Dexmedetomidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, age 0 to 180 days at the time of surgery. Diagnosis of: D-transposition of the great arteries (with or without ventricular septal defect), or tetralogy of Fallot, or ventricular septal defect (with or without associated atrial septal defect and/or patent ductus arteriosus) Scheduled for complete corrective two-ventricle surgical repair with cardiopulmonary bypass. Exclusion Criteria: 1. Less than 37 completed weeks' gestational age at birth for the Neonatal age group (0-21 days); less than 36 completed weeks' gestational age at birth for the Infant age group (22-180 days). 2. Enrollment in the PHN Collaborative Learning Study, if tetralogy of Fallot 91-180 days of age only. 3. Known or suspected hepatic dysfunction; AST and ALT >3X upper limit of normal at the time of screening within 72 hours of operation. 4. Known or suspected renal dysfunction; serum creatinine > 0.8 mg/dL after 7 days of age, >1.2 mg/dL if <7 days of age, within 72 hours of operation. 5. Preoperative administration of DEX or clonidine within 72 hours of operation. 6. Major congenital anomaly(ies) outside the cardiovascular system that in the investigator's opinion would potentially affect safety or pharmacokinetics. 7. Preoperative central nervous system injury resulting in clinical signs and symptoms: coma, seizures, hemiparesis. 8. Planned period of deep hypothermic circulatory arrest. 9. History of second or third degree heart block. 10. Sinus or junctional bradycardia below 80 BPM sustained for greater than 15 minutes within 72 hours of operation. 11. Junctional rhythm sustained for greater than 15 minutes within 72 hours of operation. 12. Hypotension defined as mean arterial blood pressure below 35 mm Hg for 0-21 day old neonatal patients, and below 40 mm Hg for 22-180 day old infant patients sustained for greater than 15 minutes within 72 hours of operation. 13. History of cardiac arrest or ECMO cannulation.

Ages Eligible for Study
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Maximum Age: 180 Days

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neonate dosing cohort 1<br>Neonate dexmedetomidine dosing cohort 1 | Drug: Dexmedetomidine<br> <br> * Other names: Precedex, dexmedetomidine HCl;|
| Experimental: Neonate dosing cohort 2<br>Neonate dexmedetomidine dosing cohort 2 | Drug: Dexmedetomidine<br> <br> * Other names: Precedex, dexmedetomidine HCl;|
| Experimental: Neonate dosing cohort 3<br>Neonate dexmedetomidine dosing cohort 3 | Drug: Dexmedetomidine<br> <br> * Other names: Precedex, dexmedetomidine HCl;|
| Experimental: Neonate dosing cohort 4<br>Neonate dexmedetomidine dosing cohort 4 | Drug: Dexmedetomidine<br> <br> * Other names: Precedex, dexmedetomidine HCl;|
| Experimental: Neonate dosing cohort 5<br>Neonate dexmedetomidine dosing cohort 5 | Drug: Dexmedetomidine<br> <br> * Other names: Precedex, dexmedetomidine HCl;|
| Experimental: Infant dosing cohort 1<br>Infant dexmedetomidine dosing cohort 1 | Drug: Dexmedetomidine<br> <br> * Other names: Precedex, dexmedetomidine HCl;|
| Experimental: Infant dosing cohort 2<br>Infant dexmedetomidine dosing cohort 2 | Drug: Dexmedetomidine<br> <br> * Other names: Precedex, dexmedetomidine HCl;|
| Experimental: Infant dosing cohort 3<br>Infant dexmedetomidine dosing cohort 3 | Drug: Dexmedetomidine<br> <br> * Other names: Precedex, dexmedetomidine HCl;|
| Experimental: Infant dosing cohort 4<br>Infant dexmedetomidine dosing cohort 4 | Drug: Dexmedetomidine<br> <br> * Other names: Precedex, dexmedetomidine HCl;|
| Experimental: Infant dosing cohort 5<br>Infant dexmedetomidine dosing cohort 5 | Drug: Dexmedetomidine<br> <br> * Other names: Precedex, dexmedetomidine HCl;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The occurrence of a safety event that is possibly, probably or definitely related to DEX administration | The occurrence of any of the following that is possibly, probably, or definitely related to DEX administration: Bradycardia Heart block Junctional rhythm Hypotension Excessive sedation Cardiac arrest or ECMO cannulation Serious Adverse Event (SAE) Both the DEX dose, and DEX exposure will be assessed for associations with the primary outcome. | Within 4 hours after DEX adminstration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of DEX | Plasma concentrations of dex obtained intraoperatively and up to 36 hours post-operatively will be used to create drug dosing models. These models will then be evaluated to determine how effective they are at achieving targeted plasma concentration levels. | Intraoperatively and up to 36 hours post-operatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatric corrective cardiac surgery