Trial Outcomes & Findings for Understanding Dexmedetomidine In Infants Post-Operative From Cardiac Surgery (NCT NCT00573066)

Results Overview

This study measured the concentration of dex in the body and used those concentrations to determine how quickly the body metabolizes and eliminates dex(concentration-time or pharmacokinetic profile).The concentration of dex in the body is determined through serial blood sampling while administering dex and following discontinuation.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

56 participants

Primary outcome timeframe

after start of infusion (0.5, 1, 2, 4-6 hours), immediately prior to end of infusion and following end of infusion (0.25, 0.5, 1, 2, 4, 8, 12, 15-18 hours)

Results posted on

2013-04-09

Participant Flow

Recruitment occurred in the CHOP cardiac center during preoperative evaluation.

All patients were evaluated postoperative to establish appropriateness for inclusion in the study.

Participant milestones

Participant milestones
Measure	Dexmedetomidine Dose Escalation Cohorts Dexmedetomidine was administered to all subjects as an intravenous loading dose over 10 minutes followed by a continuous infusion for up to 24 hours. Cohort 1--0.35mcg/kg loading dose, 0.25mcg/kg/hr infusion Cohort 2--0.7 mcg/kg loading dose, 0.5 mcg/kg/hr infusion Cohort 3--1 mcg/kg loading dose, 0.75 mcg/kg/hr infusion
Overall Study STARTED	56
Overall Study COMPLETED	36
Overall Study NOT COMPLETED	20

Reasons for withdrawal

Reasons for withdrawal
Measure	Dexmedetomidine Dose Escalation Cohorts Dexmedetomidine was administered to all subjects as an intravenous loading dose over 10 minutes followed by a continuous infusion for up to 24 hours. Cohort 1--0.35mcg/kg loading dose, 0.25mcg/kg/hr infusion Cohort 2--0.7 mcg/kg loading dose, 0.5 mcg/kg/hr infusion Cohort 3--1 mcg/kg loading dose, 0.75 mcg/kg/hr infusion
Overall Study Exclusion criteria	18
Overall Study IV malfunction	1
Overall Study Postoperative bleeding	1

Baseline Characteristics

Understanding Dexmedetomidine In Infants Post-Operative From Cardiac Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dexmedetomidine, Infants, Cardiac Surgery n=56 Participants Pharmacologic study of dexmedetomidine in infants following cardiac surgery Dexmedetomidine was administered to all subjects as an intravenous loading dose over 10 minutes followed by a continuous infusion for up to 24 hours. Cohort 1--0.35mcg/kg loading dose, 0.25mcg/kg/hr infusion Cohort 2--0.7 mcg/kg loading dose, 0.5 mcg/kg/hr infusion Cohort 3--1 mcg/kg loading dose, 0.75 mcg/kg/hr infusion
Age, Categorical <=18 years	56 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age Continuous	0.74 years STANDARD_DEVIATION 0.42 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants
Region of Enrollment United States	56 participants n=5 Participants

PRIMARY outcome

Timeframe: after start of infusion (0.5, 1, 2, 4-6 hours), immediately prior to end of infusion and following end of infusion (0.25, 0.5, 1, 2, 4, 8, 12, 15-18 hours)

Population: Based on an estimated inter-subject variability of 50% for steady state concentration, a sample size of 36 evaluable subjects will be sufficient to detect a difference (alpha 0.05, power 0.8) for the area under the concentration-time curve (AUC) and steady state concentration (Css) between the three dosing groups.

This study measured the concentration of dex in the body and used those concentrations to determine how quickly the body metabolizes and eliminates dex(concentration-time or pharmacokinetic profile).The concentration of dex in the body is determined through serial blood sampling while administering dex and following discontinuation.

Outcome measures

Outcome measures
Measure	Dexmedetomidine, Infants, Cardiac Surgery n=56 Participants Pharmacologic study of dexmedetomidine in infants following cardiac surgery Dexmedetomidine was administered to all subjects as an intravenous loading dose over 10 minutes followed by a continuous infusion for up to 24 hours. Cohort 1--0.35mcg/kg loading dose, 0.25mcg/kg/hr infusion Cohort 2--0.7 mcg/kg loading dose, 0.5 mcg/kg/hr infusion Cohort 3--1 mcg/kg loading dose, 0.75 mcg/kg/hr infusion
PK Profile of Dexmedetomidine	28 mL/min/(kg^0.75) Standard Error 0.08

Adverse Events

Dexmedetomidine, Infants, Cardiac Surgery

Serious events: 3 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dexmedetomidine, Infants, Cardiac Surgery n=56 participants at risk Pharmacologic study of dexmedetomidine in infants following cardiac surgery Dexmedetomidine was administered to all subjects as an intravenous loading dose over 10 minutes followed by a continuous infusion for up to 24 hours. Cohort 1--0.35mcg/kg loading dose, 0.25mcg/kg/hr infusion Cohort 2--0.7 mcg/kg loading dose, 0.5 mcg/kg/hr infusion Cohort 3--1 mcg/kg loading dose, 0.75 mcg/kg/hr infusion
Cardiac disorders Hypotension	3.6% 2/56 • Number of events 2 • Data collected for up to 30 days following end of dexmedetomidine administration All adverse events possibly, probably and definitely related are included.
Respiratory, thoracic and mediastinal disorders Bradypnea/Oversedation	1.8% 1/56 • Number of events 1 • Data collected for up to 30 days following end of dexmedetomidine administration All adverse events possibly, probably and definitely related are included.

Other adverse events

Other adverse events
Measure	Dexmedetomidine, Infants, Cardiac Surgery n=56 participants at risk Pharmacologic study of dexmedetomidine in infants following cardiac surgery Dexmedetomidine was administered to all subjects as an intravenous loading dose over 10 minutes followed by a continuous infusion for up to 24 hours. Cohort 1--0.35mcg/kg loading dose, 0.25mcg/kg/hr infusion Cohort 2--0.7 mcg/kg loading dose, 0.5 mcg/kg/hr infusion Cohort 3--1 mcg/kg loading dose, 0.75 mcg/kg/hr infusion
Cardiac disorders Complete heart block	1.8% 1/56 • Number of events 1 • Data collected for up to 30 days following end of dexmedetomidine administration All adverse events possibly, probably and definitely related are included.
Cardiac disorders Cardiac ischemia	5.4% 3/56 • Number of events 3 • Data collected for up to 30 days following end of dexmedetomidine administration All adverse events possibly, probably and definitely related are included.
Cardiac disorders Accelerated junctional rhythm	1.8% 1/56 • Number of events 1 • Data collected for up to 30 days following end of dexmedetomidine administration All adverse events possibly, probably and definitely related are included.

Additional Information

Athena Zuppa

Children's Hospital of Philadelphia

Phone: 267-426-7359

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place