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

Carelon Research

Status and phase: Completed; Phase 1

Conditions: Tetralogy of Fallot; Transposition of the Great Arteries; Ventricular Septal Defect

Treatments: Drug: Dexmedetomidine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01915277

PHN-DEX

Details and patient eligibility

About

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.

Enrollment: 119 patients

Sex: All

Ages: Under 180 days old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male or female, age 0 to 180 days at the time of surgery.
2. 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)
3. 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.

  9. 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.

  10. History of cardiac arrest or ECMO cannulation.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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119 participants in 10 patient groups

Neonate dosing cohort 1

Experimental group

Description:

Neonate dexmedetomidine dosing cohort 1

Treatment:

Drug: Dexmedetomidine

Neonate dosing cohort 2

Experimental group

Description:

Neonate dexmedetomidine dosing cohort 2

Treatment:

Drug: Dexmedetomidine

Neonate dosing cohort 3

Experimental group

Description:

Neonate dexmedetomidine dosing cohort 3

Treatment:

Drug: Dexmedetomidine

Neonate dosing cohort 4

Experimental group

Description:

Neonate dexmedetomidine dosing cohort 4

Treatment:

Drug: Dexmedetomidine

Neonate dosing cohort 5

Experimental group

Description:

Neonate dexmedetomidine dosing cohort 5

Treatment:

Drug: Dexmedetomidine

Infant dosing cohort 1

Experimental group

Description:

Infant dexmedetomidine dosing cohort 1

Treatment:

Drug: Dexmedetomidine

Infant dosing cohort 2

Experimental group

Description:

Infant dexmedetomidine dosing cohort 2

Treatment:

Drug: Dexmedetomidine

Infant dosing cohort 3

Experimental group

Description:

Infant dexmedetomidine dosing cohort 3

Treatment:

Drug: Dexmedetomidine

Infant dosing cohort 4

Experimental group

Description:

Infant dexmedetomidine dosing cohort 4

Treatment:

Drug: Dexmedetomidine

Infant dosing cohort 5

Experimental group

Description:

Infant dexmedetomidine dosing cohort 5

Treatment:

Drug: Dexmedetomidine