Clinical trial NCT01915277: A Phase I Study of Dexmedetomidine Bolus and Infusion in Corrective Infant Cardiac Surgery: Safety and Pharmacokinetics
Official title: A Phase I Study of Dexmedetomidine Bolus and Infusion in Corrective Infant Cardiac Surgery: Safety and Pharmacokinetics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Transposition of the Great Arteries
Tetralogy of Fallot
Ventricular Septal Defect
Keywords: Pediatric corrective cardiac surgery
Lead sponsor: Carelon Research
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2013-08-02
Enrollment: 119
Sex: ALL
Maximum age (years): 180
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

  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.

Primary outcomes:
measure: The occurrence of a safety event that is possibly, probably or definitely related to DEX administration
timeFrame: Within 4 hours after DEX adminstration
Secondary outcomes:
measure: Plasma concentration of DEX
timeFrame: Intraoperatively and up to 36 hours post-operatively
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Philadelphia
country: United States
facility: Childrens Hospital of Philadelphia
state: Pennsylvania
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
Study officials:
References:
citation: Zuppa AF, Nicolson SC, Wilder NS, Ibla JC, Gottlieb EA, Burns KM, Stylianou M, Trachtenberg F, Ni H, Skeen TH, Andropoulos DB; Pediatric Heart Network Investigators. Results of a phase 1 multicentre investigation of dexmedetomidine bolus and infusion in corrective infant cardiac surgery. Br J Anaesth. 2019 Dec;123(6):839-852. doi: 10.1016/j.bja.2019.06.026. Epub 2019 Oct 14.