Trial Outcomes & Findings for Understanding Dexmedetomidine in Neonates After Open Heart Surgery (NCT NCT00576381)

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

30 participants

Primary outcome timeframe

A sparse PK sampling method was utilized. Between 6-12 PK samples were drawn : After start of infusion (0.5, 4-6, 8 hours), immediately prior to end of infusion and following end of infusion (0.25, 0.5, 1, 2-4, 6-8, 10-12 & 18hrs)

Results posted on

2013-04-18

Participant Flow

All subjects were recruited from inpatient cardiac intensive care unit prior to open heart surgery.

Participant milestones

Participant milestones
Measure	Neonatal Dose Escalation Cohorts Neonates will be administered a single bolus dose of dexmedetomidine followed by a continuous infusion for up to 24 hours post cardiac surgery. Cohort 1--0.25 mcg/kg loading dose, 0.2 mcg/kg/hr infusion Cohort 1A--0.35 mcg/kg loading dose, 0.3 mcg/kg/hr infusion Cohort 2--0.5 mcg/kg loading dose, 0.4 mcg/kg/hr infusion
Overall Study STARTED	30
Overall Study COMPLETED	23
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Neonatal Dose Escalation Cohorts Neonates will be administered a single bolus dose of dexmedetomidine followed by a continuous infusion for up to 24 hours post cardiac surgery. Cohort 1--0.25 mcg/kg loading dose, 0.2 mcg/kg/hr infusion Cohort 1A--0.35 mcg/kg loading dose, 0.3 mcg/kg/hr infusion Cohort 2--0.5 mcg/kg loading dose, 0.4 mcg/kg/hr infusion
Overall Study Reoperation	3
Overall Study Adverse Event	4

Baseline Characteristics

Understanding Dexmedetomidine in Neonates After Open Heart Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dosing Cohorts n=30 Participants Neonates will be administered a single bolus dose of dexmedetomidine followed by a continuous infuusion for up to 24 hours post cardiac surgery. Dexmedetomidine : Dosage Level 1=0.25mcg/kg loading dose, 0.2 mcg/kg/hr infusion Dosage Level 1A= 0.35mcg/kg loading dose, 0.3 mcg/kg/hr infusion Dosage Level 2= 0.5mcg/kg loading dose, 0.4 mcg/kg/hr infusion
Age, Categorical <=18 years	30 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
Sex: Female, Male Female	14 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants
Region of Enrollment United States	30 participants n=5 Participants

PRIMARY outcome

Timeframe: A sparse PK sampling method was utilized. Between 6-12 PK samples were drawn : After start of infusion (0.5, 4-6, 8 hours), immediately prior to end of infusion and following end of infusion (0.25, 0.5, 1, 2-4, 6-8, 10-12 & 18hrs)

Population: Based on an estimated inter-subject variability of 50% for clearance, a sample size of 32 evaluable subjects will be sufficient to detect an 18% difference (alpha 0.05, power 0.9) in the clearance in this population (38 + 18 L/hr) versus that previously reported in the adult population (46 L/hr).

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	Neonates n=30 Participants Neonates will be administered a single bolus dose of dexmedetomidine followed by a continuous infuusion for up to 24 hours post cardiac surgery. Cohort 1--0.25mcg/kg loading dose, 0.2mcg/kg/hr infusion Cohort 1A--0.35 mcg/kg loading dose, 0.3 mcg/kg/hr infusion Cohort 2--0.5 mcg/kg loading dose, 0.4 mcg/kg/hr infusion
PK Profile of Dexmedetomidine	110 mL/min Standard Error 6.24 • Interval 88.0 to 128.0

Adverse Events

Dosing Cohorts

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dosing Cohorts n=30 participants at risk Neonates will be administered a single bolus dose of dexmedetomidine followed by a continuous infuusion for up to 24 hours post cardiac surgery. Dexmedetomidine : Dosage Level 1=0.25mcg/kg loading dose, 0.2 mcg/kg/hr infusion Dosage Level 1A= 0.35mcg/kg loading dose, 0.3 mcg/kg/hr infusion Dosage Level 2= 0.5mcg/kg loading dose, 0.4 mcg/kg/hr infusion
Cardiac disorders Atrial ectopy	6.7% 2/30 • Number of events 2

Other adverse events

Other adverse events
Measure	Dosing Cohorts n=30 participants at risk Neonates will be administered a single bolus dose of dexmedetomidine followed by a continuous infuusion for up to 24 hours post cardiac surgery. Dexmedetomidine : Dosage Level 1=0.25mcg/kg loading dose, 0.2 mcg/kg/hr infusion Dosage Level 1A= 0.35mcg/kg loading dose, 0.3 mcg/kg/hr infusion Dosage Level 2= 0.5mcg/kg loading dose, 0.4 mcg/kg/hr infusion
Cardiac disorders myocardial ischemia	3.3% 1/30 • Number of events 1
Cardiac disorders accelerated junctional rhythm	6.7% 2/30 • Number of events 2

Additional Information

Dr Athena Zuppa

The Children's Hospital of Philadelphia

Phone: 267-426-5753

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place