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

Phase 1

Completed

• Conditions: Transposition of the Great Arteries; Ventricular Septal Defect; Tetralogy of Fallot
• Interventions: Drug: Dexmedetomidine

• Registration Number: NCT01915277
• Lead Sponsor: Carelon Research

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-07-30
• Study First Submitted QC: 2013-07-31
• Study First Posted: 2013-08-02
• Study Start: 2014-04-02
• Primary Completion: 2017-10-16
• Study Completion: 2017-10-17
• Status Verified: 2018-03
• Last Update Submitted: 2018-03-21
• Last Update Posted: 2018-03-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 119

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Neonate dosing cohort 5	Dexmedetomidine	Neonate dexmedetomidine dosing cohort 5
Neonate dosing cohort 2	Dexmedetomidine	Neonate dexmedetomidine dosing cohort 2
Infant dosing cohort 4	Dexmedetomidine	Infant dexmedetomidine dosing cohort 4
Neonate dosing cohort 1	Dexmedetomidine	Neonate dexmedetomidine dosing cohort 1
Neonate dosing cohort 3	Dexmedetomidine	Neonate dexmedetomidine dosing cohort 3
Neonate dosing cohort 4	Dexmedetomidine	Neonate dexmedetomidine dosing cohort 4
Infant dosing cohort 1	Dexmedetomidine	Infant dexmedetomidine dosing cohort 1
Infant dosing cohort 2	Dexmedetomidine	Infant dexmedetomidine dosing cohort 2
Infant dosing cohort 5	Dexmedetomidine	Infant dexmedetomidine dosing cohort 5
Infant dosing cohort 3	Dexmedetomidine	Infant dexmedetomidine dosing cohort 3

Primary Outcome Measures

Name	Time	Method
The occurrence of a safety event that is possibly, probably or definitely related to DEX administration	Within 4 hours after DEX adminstration	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.

Secondary Outcome Measures

Name	Time	Method
Plasma concentration of DEX	Intraoperatively and up to 36 hours post-operatively	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.

Trial Locations

Locations (4)

Texas Children's Hospital; 🇺🇸 Houston, Texas, United States

Childrens Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Boston Children's Hospital; 🇺🇸 Boston, Massachusetts, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States