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

Tetralogy of Fallot Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01915277
• Other study ID #: PHN-DEX
• Status: Completed
• Phase: Phase 1
• First received: July 30, 2013
• Last updated: March 21, 2018
• Start date: April 2, 2014
• Est. completion date: October 17, 2017

Study information

• Verified date: March 2018
• Source: New England Research Institutes
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 119
• Est. completion date: October 17, 2017
• Est. primary completion date: October 16, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 180 Days

Eligibility

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.

Related Conditions & MeSH terms

• Heart Septal Defects
• Heart Septal Defects, Ventricular
• Tetralogy of Fallot
• Transposition of Great Vessels
• Transposition of the Great Arteries
• Ventricular Septal Defect

Intervention

Drug:
• Dexmedetomidine

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Texas Children's Hospital	Houston	Texas
United States	Childrens Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
New England Research Institutes	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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