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

Primary Purpose

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

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Dexmedetomidine
Sponsored by
Carelon Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Transposition of the Great Arteries focused on measuring Pediatric corrective cardiac surgery

Eligibility Criteria

undefined - 180 Days (Child)All SexesDoes not accept 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.

    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.

Sites / Locations

  • Boston Children's Hospital
  • University of Michigan
  • Childrens Hospital of Philadelphia
  • Texas Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Neonate dosing cohort 1

Neonate dosing cohort 2

Neonate dosing cohort 3

Neonate dosing cohort 4

Neonate dosing cohort 5

Infant dosing cohort 1

Infant dosing cohort 2

Infant dosing cohort 3

Infant dosing cohort 4

Infant dosing cohort 5

Arm Description

Neonate dexmedetomidine dosing cohort 1

Neonate dexmedetomidine dosing cohort 2

Neonate dexmedetomidine dosing cohort 3

Neonate dexmedetomidine dosing cohort 4

Neonate dexmedetomidine dosing cohort 5

Infant dexmedetomidine dosing cohort 1

Infant dexmedetomidine dosing cohort 2

Infant dexmedetomidine dosing cohort 3

Infant dexmedetomidine dosing cohort 4

Infant dexmedetomidine dosing cohort 5

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
July 30, 2013
Last Updated
March 21, 2018
Sponsor
Carelon Research
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT01915277
Brief Title
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

2. Study Status

Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
April 2, 2014 (Actual)
Primary Completion Date
October 16, 2017 (Actual)
Study Completion Date
October 17, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Carelon Research
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Transposition of the Great Arteries, Tetralogy of Fallot, Ventricular Septal Defect
Keywords
Pediatric corrective cardiac surgery

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
119 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Neonate dosing cohort 1
Arm Type
Experimental
Arm Description
Neonate dexmedetomidine dosing cohort 1
Arm Title
Neonate dosing cohort 2
Arm Type
Experimental
Arm Description
Neonate dexmedetomidine dosing cohort 2
Arm Title
Neonate dosing cohort 3
Arm Type
Experimental
Arm Description
Neonate dexmedetomidine dosing cohort 3
Arm Title
Neonate dosing cohort 4
Arm Type
Experimental
Arm Description
Neonate dexmedetomidine dosing cohort 4
Arm Title
Neonate dosing cohort 5
Arm Type
Experimental
Arm Description
Neonate dexmedetomidine dosing cohort 5
Arm Title
Infant dosing cohort 1
Arm Type
Experimental
Arm Description
Infant dexmedetomidine dosing cohort 1
Arm Title
Infant dosing cohort 2
Arm Type
Experimental
Arm Description
Infant dexmedetomidine dosing cohort 2
Arm Title
Infant dosing cohort 3
Arm Type
Experimental
Arm Description
Infant dexmedetomidine dosing cohort 3
Arm Title
Infant dosing cohort 4
Arm Type
Experimental
Arm Description
Infant dexmedetomidine dosing cohort 4
Arm Title
Infant dosing cohort 5
Arm Type
Experimental
Arm Description
Infant dexmedetomidine dosing cohort 5
Intervention Type
Drug
Intervention Name(s)
Dexmedetomidine
Other Intervention Name(s)
Precedex, dexmedetomidine HCl
Primary Outcome Measure Information:
Title
The occurrence of a safety event that is possibly, probably or definitely related to DEX administration
Description
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.
Time Frame
Within 4 hours after DEX adminstration
Secondary Outcome Measure Information:
Title
Plasma concentration of DEX
Description
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.
Time Frame
Intraoperatively and up to 36 hours post-operatively

10. Eligibility

Sex
All
Maximum Age & Unit of Time
180 Days
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Childrens Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
31623840
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.
Results Reference
derived

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

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