Trial Outcomes & Findings for Safety of Clonidine in Infants With Hypoxic Ischemic Encephalopathy During Therapeutic Hypothermia (NCT NCT01862250)

Last Updated: 2018-01-05

Results Overview

Trough clonidine blood levels were measured after 4-7 doses of clonidine were given intravenously with a dosing interval of every 8 hrs. Mean and standard deviation (SD) of the number of doses given prior to levels being drawn was 5.3 (mean) and 0.37 (SD). Time after last dose before measurement was 9hrs (mean) and 2.7hrs (SD).

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

13 participants

Primary outcome timeframe

3 days

Results posted on

2018-01-05

Participant Flow

Study medication was not administered for one participant

Participant milestones

Participant milestones
Measure	Clonidine Infants With HIE Infants in this group will receive Intravenous clonidine at 1µg/kg/dose either every 6 or 8 hrs from the start of cooling to the end of re-warming Clonidine (Duraclon®): Clonidine at dosing intervals of 6, 8, 12, 18 or 24 hours. If the following is observed the event will be recorded, and no additional clonidine will be given and blood will be drawn to measure plasma level of clondine. * 10 mm Hg reduction in Mean Arterial Pressure (MAP) or MAP ≤ 40 mm Hg sustained for ≥30 min after administration * 20% drop in Heart Rate (HR) from the infant's baseline, sustained for ≥30 min after administration * HR ≤70/min, sustained for ≥30 min after administration
Overall Study STARTED	12
Overall Study COMPLETED	8
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Clonidine Infants With HIE Infants in this group will receive Intravenous clonidine at 1µg/kg/dose either every 6 or 8 hrs from the start of cooling to the end of re-warming Clonidine (Duraclon®): Clonidine at dosing intervals of 6, 8, 12, 18 or 24 hours. If the following is observed the event will be recorded, and no additional clonidine will be given and blood will be drawn to measure plasma level of clondine. * 10 mm Hg reduction in Mean Arterial Pressure (MAP) or MAP ≤ 40 mm Hg sustained for ≥30 min after administration * 20% drop in Heart Rate (HR) from the infant's baseline, sustained for ≥30 min after administration * HR ≤70/min, sustained for ≥30 min after administration
Overall Study Adverse Event	4

Baseline Characteristics

Safety of Clonidine in Infants With Hypoxic Ischemic Encephalopathy During Therapeutic Hypothermia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Clonidine Infants With HIE n=12 Participants Infants in this group will receive Intravenous clonidine at 1µg/kg/dose either every 6 or 8 hrs from the start of cooling to the end of re-warming Clonidine (Duraclon®): Clonidine at dosing intervals of 4, 6, 8, 12, 18 or 24 hours. If the following is observed the event will be recorded, and no additional clonidine will be given and blood will be drawn to measure plasma level of clondine. * 10 mm Hg reduction in MAP or MAP ≤ 40 mm Hg sustained for ≥30 min after administration * 20% drop in HR from the infant's baseline, sustained for ≥30 min after administration * HR ≤70/min, sustained for ≥30 min after administration
Age, Continuous	38.2 weeks n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants

PRIMARY outcome

Timeframe: 3 days

Population: Only 8 babies were assessed for this outcome because the rest did not have a steady state trough level performed during cooling

Outcome measures

Outcome measures
Measure	Clonidine Infants With HIE n=8 Participants Infants in this group will receive Intravenous clonidine at 1µg/kg/dose either every 6 or 8 hrs from the start of cooling to the end of re-warming Clonidine (Duraclon®): Clonidine at dosing intervals of 4, 6, 8, 12, 18 or 24 hours. If the following is observed the event will be recorded, and no additional clonidine will be given and blood will be drawn to measure plasma level of clondine. * 10 mm Hg reduction in MAP or MAP ≤ 40 mm Hg sustained for ≥30 min after administration * 20% drop in HR from the infant's baseline, sustained for ≥30 min after administration * HR ≤70/min, sustained for ≥30 min after administration
Steady State Clonidine Blood Levels During Hypothermia	0.6 ng/ml Interval 0.27 to 1.06

PRIMARY outcome

Timeframe: Up to 2 days

Intravenous morphine (mg/kg) was given. The standard dose is 0.05 mg/kg per dose

Outcome measures

Outcome measures
Measure	Clonidine Infants With HIE n=8 Participants Infants in this group will receive Intravenous clonidine at 1µg/kg/dose either every 6 or 8 hrs from the start of cooling to the end of re-warming Clonidine (Duraclon®): Clonidine at dosing intervals of 4, 6, 8, 12, 18 or 24 hours. If the following is observed the event will be recorded, and no additional clonidine will be given and blood will be drawn to measure plasma level of clondine. * 10 mm Hg reduction in MAP or MAP ≤ 40 mm Hg sustained for ≥30 min after administration * 20% drop in HR from the infant's baseline, sustained for ≥30 min after administration * HR ≤70/min, sustained for ≥30 min after administration
Amount of Morphine Given	0.02 mg/kg Interval 0.0 to 0.08

SECONDARY outcome

Timeframe: 48hrs

Babies were assessed after administration of clonidine for the presence or absence of shivering.

Outcome measures

Outcome measures
Measure	Clonidine Infants With HIE n=12 Participants Infants in this group will receive Intravenous clonidine at 1µg/kg/dose either every 6 or 8 hrs from the start of cooling to the end of re-warming Clonidine (Duraclon®): Clonidine at dosing intervals of 4, 6, 8, 12, 18 or 24 hours. If the following is observed the event will be recorded, and no additional clonidine will be given and blood will be drawn to measure plasma level of clondine. * 10 mm Hg reduction in MAP or MAP ≤ 40 mm Hg sustained for ≥30 min after administration * 20% drop in HR from the infant's baseline, sustained for ≥30 min after administration * HR ≤70/min, sustained for ≥30 min after administration
Presence of Shivering After Clonidine	0 Participants

SECONDARY outcome

Timeframe: Beginning at 72 hours up to 12 hours

Following 2 hours of therapeutic hypothermia, the temperature of the thermo-blanket is adjusted up half degree per hour allowing passive rewarming until 36.5 degrees is reached

Outcome measures

Outcome measures
Measure	Clonidine Infants With HIE n=8 Participants Infants in this group will receive Intravenous clonidine at 1µg/kg/dose either every 6 or 8 hrs from the start of cooling to the end of re-warming Clonidine (Duraclon®): Clonidine at dosing intervals of 4, 6, 8, 12, 18 or 24 hours. If the following is observed the event will be recorded, and no additional clonidine will be given and blood will be drawn to measure plasma level of clondine. * 10 mm Hg reduction in MAP or MAP ≤ 40 mm Hg sustained for ≥30 min after administration * 20% drop in HR from the infant's baseline, sustained for ≥30 min after administration * HR ≤70/min, sustained for ≥30 min after administration
Time to Passive Rewarming	8.7 Hours Interval 7.4 to 10.1

Adverse Events

Clonidine Infants With HIE

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Estelle B. Gauda

University of Toronto

Phone: 416-813-4908

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place