Trial Outcomes & Findings for DOSE Trial of Opioid Sparing Effect (NCT NCT03938857)

Results Overview

Characterize the opioid-sparing effect of dexmedetomidine when co-administered with fentanyl in children receiving mechanical ventilation. Characterization of differences between dosing exposures for the four groups will allow estimation of the opioid-sparing effect of dexmedetomidine.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

30 participants

Primary outcome timeframe

through day 7 of mechanical ventilation or initial extubation (whichever is first)

Results posted on

2021-11-05

Participant Flow

Subjects enrolled were in a pediatric intensive care setting, critically ill and requiring ventilatory support and pain management associated with such.

Participant milestones

Participant milestones
Measure	Fen. SOC+Saline Placebo (Bolus+Infusion) Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr) Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr) Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)
Overall Study STARTED	6	12	12
Overall Study COMPLETED	5	12	12
Overall Study NOT COMPLETED	1	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Fen. SOC+Saline Placebo (Bolus+Infusion) Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr) Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr) Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Overall Study Physician Decision	1	0	0	0

Baseline Characteristics

DOSE Trial of Opioid Sparing Effect

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fen. SOC+Saline Placebo (Bolus+Infusion) n=6 Participants Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr) n=12 Participants Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr) n=12 Participants Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)	Total n=30 Participants Total of all reporting groups
Age, Continuous	3.8 years STANDARD_DEVIATION 6.8 • n=5 Participants	2.5 years STANDARD_DEVIATION 2.8 • n=7 Participants	2.6 years STANDARD_DEVIATION 3.7 • n=5 Participants	—	2.8 years STANDARD_DEVIATION 4.0 • n=21 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	—	12 Participants n=21 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	—	18 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	—	2 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	11 Participants n=7 Participants	10 Participants n=5 Participants	—	26 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	—	2 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	—	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	—	0 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	—	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	—	7 Participants n=21 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants	—	19 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	—	1 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	—	3 Participants n=21 Participants
Region of Enrollment United States	6 Participants n=5 Participants	12 Participants n=7 Participants	12 Participants n=5 Participants	—	30 Participants n=21 Participants

PRIMARY outcome

Timeframe: through day 7 of mechanical ventilation or initial extubation (whichever is first)

Population: Patients who did not have fentanyl reported were excluded. No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.

Characterize the opioid-sparing effect of dexmedetomidine when co-administered with fentanyl in children receiving mechanical ventilation. Characterization of differences between dosing exposures for the four groups will allow estimation of the opioid-sparing effect of dexmedetomidine.

Outcome measures

Outcome measures
Measure	Fen. SOC+Saline Placebo (Bolus+Infusion) n=6 Participants Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr) n=12 Participants Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr) n=12 Participants Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Mean Daily Dose of Fentanyl in mcg/kg/hr (Micrograms Per Kilogram Per Hour)	2.25 mcg/kg/hr Standard Deviation 2.15	2.68 mcg/kg/hr Standard Deviation 1.53	3.23 mcg/kg/hr Standard Deviation 3.30	—

SECONDARY outcome

Timeframe: through day 7 of mechanical ventilation or initial extubation (whichever is first)

Population: Data not collected. The study was terminated early due to enrollment challenges.

Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The SBS is a 6-point scale that ranges from +2 to -3 with -3. Scores that are more negative reflect a more sedated state (-3). Scores that are more positive reflect a more agitated state (+2). Zero is awake and easily calmed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: through day 7 of mechanical ventilation or initial extubation (whichever is first)

Population: Data not collected. The study was terminated early due to enrollment challenges.

Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The SBS is a 6-point scale that ranges from +2 to -3 with -3. Scores that are more negative reflect a more sedated state (-3). Scores that are more positive reflect a more agitated state (+2). Zero is awake and easily calmed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: through day 7 of mechanical ventilation or initial extubation (whichever is first)

Population: Data not collected. The study was terminated early due to enrollment challenges.

Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The SBS is a 6-point scale that ranges from +2 to -3 with -3. Scores that are more negative reflect a more sedated state (-3). Scores that are more positive reflect a more agitated state (+2). Zero is awake and easily calmed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: through day 7 of mechanical ventilation or initial extubation (whichever is first)

Population: Data not collected. The study was terminated early due to enrollment challenges.

Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The SBS is a 6-point scale that ranges from +2 to -3 with -3. Scores that are more negative reflect a more sedated state (-3). Scores that are more positive reflect a more agitated state (+2). Zero is awake and easily calmed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: through day 7 of mechanical ventilation or initial extubation (whichever is first)

Population: Data not collected. The study was terminated early due to enrollment challenges.

Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The SBS is a 6-point scale that ranges from +2 to -3 with -3. Scores that are more negative reflect a more sedated state (-3). Scores that are more positive reflect a more agitated state (+2). Zero is awake and easily calmed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: through day 7 of mechanical ventilation or initial extubation (whichever is first)

Population: Data not collected. The study was terminated early due to enrollment challenges.

Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The SBS is a 6-point scale that ranges from +2 to -3 with -3. Scores that are more negative reflect a more sedated state (-3). Scores that are more positive reflect a more agitated state (+2). Zero is awake and easily calmed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: through day 7 of mechanical ventilation or initial extubation (whichever is first)

Population: Data not collected. The study was terminated early due to enrollment challenges.

Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The SBS is a 6-point scale that ranges from +2 to -3 with -3. Scores that are more negative reflect a more sedated state (-3). Scores that are more positive reflect a more agitated state (+2). Zero is awake and easily calmed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: through day 7 of mechanical ventilation or initial extubation (whichever is first)

Population: Data not collected. The study was terminated early due to enrollment challenges.

Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The SBS is a 6-point scale that ranges from +2 to -3 with -3. Scores that are more negative reflect a more sedated state (-3). Scores that are more positive reflect a more agitated state (+2). Zero is awake and easily calmed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: through day 7 of mechanical ventilation or initial extubation (whichever is first)

Population: Data not collected. The study was terminated early due to enrollment challenges.

Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The RASS is a 10-point scale that ranges from -5 to +4 with -5=unarousable and +4=combative. Zero means the patient is alert and calm.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: through day 7 of mechanical ventilation or initial extubation (whichever is first)

Population: Data not collected. The study was terminated early due to enrollment challenges.

Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The RASS scale is a 10-pint scale that ranges from -5 to +4 with -5=unarousable and +4=combative. Zero means the patient is alert and calm.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: through day 7 of mechanical ventilation or initial extubation (whichever is first)

Population: Data not collected. The study was terminated early due to enrollment challenges.

Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The RASS scale is a 10-point scale that ranges from -5 to +4 with -5=unarousable and +4=combative. Zero means the patient is alert and calm.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: through day 7 of mechanical ventilation or initial extubation (whichever is first)

Population: Data not collected. The study was terminated early due to enrollment challenges.

Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The RASS scale is a 10-point scale that ranges from -5 to +4 with -5=unarousable and +4=combative. Zero means the patient is alert and calm.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: through day 7 of mechanical ventilation or initial extubation (whichever is first)

Population: Data not collected. The study was terminated early due to enrollment challenges.

Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The RASS scale is a 10-point scale that ranges from -5 to +4 with -5=unarousable and +4=combative. Zero means the patient is alert and calm.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: through day 7 of mechanical ventilation or initial extubation (whichever is first)

Population: Data not collected. The study was terminated early due to enrollment challenges.

Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The RASS scale is a 10-point scale that ranges from -5 to +4 with -5=unarousable and +4=combative. Zero means the patient is alert and calm.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: through day 7 of mechanical ventilation or initial extubation (whichever is first)

Population: Data not collected. The study was terminated early due to enrollment challenges.

Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The RASS scale is a 10-point scale that ranges from -5 to +4 with -5=unarousable and +4=combative. Zero means the patient is alert and calm.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: through day 7 of mechanical ventilation or initial extubation (whichever is first)

Population: Data not collected. The study was terminated early due to enrollment challenges.

Characterize the exposure response relationships of fentanyl and dexmedetomidine when administered alone or in combination in children receiving mechanical ventilation. PK is known to be altered in children compared to adults, and in those with critical illness. Characterization of pharmacokinetic-pharmacodynamic relationships can improve dose optimization when dose may not be equivalent to plasma exposure and related effect. The RASS scale is a 10-point scale that ranges from -5 to +4 with -5=unarousable and +4=combative. Zero means the patient is alert and calm.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 28 days or until discharge from the ICU (whichever is first)

Population: Participants with data collected. No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.

Characterize the safety profile of fentanyl and dexmedetomidine when administered alone or in combination to children receiving mechanical ventilation.

Outcome measures

Outcome measures
Measure	Fen. SOC+Saline Placebo (Bolus+Infusion) n=5 Participants Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr) n=12 Participants Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr) n=12 Participants Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Number of Participants Experiencing a Clinically Significant Episode of Hypotension	2 Participants	5 Participants	3 Participants	—

SECONDARY outcome

Timeframe: up to 28 days or until discharge from the ICU (whichever is first)

Population: No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.

Outcome measures

Outcome measures
Measure	Fen. SOC+Saline Placebo (Bolus+Infusion) n=6 Participants Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr) n=12 Participants Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr) n=12 Participants Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Number of Participants Experiencing SAEs (Serious Adverse Events)	0 Participants	2 Participants	1 Participants	—

SECONDARY outcome

Timeframe: up to 28 days or until discharge from the ICU (whichever is first)

Population: Participants who experienced at least one SAE. No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.

Outcome measures

Outcome measures
Measure	Fen. SOC+Saline Placebo (Bolus+Infusion) Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr) n=2 Participants Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr) n=1 Participants Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Mean Number of SAEs (Serious Adverse Events) Experienced by Participants	—	1 serious adverse events Standard Deviation 0	1 serious adverse events Standard Deviation NA Only one participant experienced an SAE.	—

SECONDARY outcome

Timeframe: up to 28 days or until discharge from the ICU (whichever is first)

Population: Participants with data collected. No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.

Characterize the safety profile of fentanyl and dexmedetomidine when administered alone or in combination to children receiving mechanical ventilation.

Outcome measures

Outcome measures
Measure	Fen. SOC+Saline Placebo (Bolus+Infusion) n=5 Participants Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr) n=12 Participants Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr) n=12 Participants Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Number of Participants Experiencing a Clinically Significant Episode of Bradycardia	2 Participants	3 Participants	1 Participants	—

SECONDARY outcome

Timeframe: up to 28 days or until discharge from the ICU (whichever is first)

Population: Participants with data collected. No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.

Characterize the safety profile of fentanyl and dexmedetomidine when administered alone or in combination to children receiving mechanical ventilation.

Outcome measures

Outcome measures
Measure	Fen. SOC+Saline Placebo (Bolus+Infusion) n=5 Participants Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr) n=11 Participants Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr) n=11 Participants Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Number of Participants Experiencing a Clinically Significant Episode of Urinary Retention	1 Participants	2 Participants	1 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: through day 7 of mechanical ventilation or initial extubation (whichever is first)

Estimate the incidence of intensive care unit delirium in children exposed to fentanyl and dexmedetomidine alone or in combination when receiving mechanical ventilation. (Measures of delirium). The CAPD scale goes from 0-4 and has 8 questions. All items scored as occurring never, rarely, sometimes, often, or always. Individual item scores are added for a sum total score.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: through day 7 of mechanical ventilation or initial extubation (whichever is first)

Estimate the incidence of intensive care unit delirium in children exposed to fentanyl and dexmedetomidine alone or in combination when receiving mechanical ventilation. (Measures of delirium). The CAPD scale goes from 0-4 and has 8 questions. All items scored as occurring never, rarely, sometimes, often, or always. Individual item scores are added for a sum total score.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: through day 7 of mechanical ventilation or initial extubation (whichever is first)

Estimate the incidence of intensive care unit delirium in children exposed to fentanyl and dexmedetomidine alone or in combination when receiving mechanical ventilation. (Measures of delirium). The CAPD scale goes from 0-4 and has 8 questions. All items scored as occurring never, rarely, sometimes, often, or always. Individual item scores are added for a sum total score.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: through day 7 of mechanical ventilation or initial extubation (whichever is first)

Estimate the incidence of opioid withdrawal syndrome in children exposed to fentanyl and dexmedetomidine when administered alone or in combination when receiving mechanical ventilation. (Measures of withdrawal). WAT-1 scale is 0=no/none and 1=yes/moderate/severe. Total score is on a 0-12 scale where lower is better.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: through day 7 of mechanical ventilation or initial extubation (whichever is first)

Estimate the incidence of opioid withdrawal syndrome in children exposed to fentanyl and dexmedetomidine when administered alone or in combination when receiving mechanical ventilation. (Measures of withdrawal). WAT-1 scale is 0=no/none and 1=yes/moderate/severe. Total score is on a 0-12 scale where lower is better.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: through day 7 of mechanical ventilation or initial extubation (whichever is first)

Estimate the incidence of opioid withdrawal syndrome in children exposed to fentanyl and dexmedetomidine when administered alone or in combination when receiving mechanical ventilation. (Measures of withdrawal). WAT-1 scale is 0=no/none and 1=yes/moderate/severe. Total score is on a 0-12 scale where lower is better.

Outcome measures

Outcome data not reported

Adverse Events

Fen. SOC+Saline Placebo (Bolus+Infusion)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr)

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr)

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Fen. SOC+Saline Placebo (Bolus+Infusion) n=6 participants at risk Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr) n=12 participants at risk Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr) n=12 participants at risk Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
General disorders General signs and symptoms NEC	0.00% 0/6 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	8.3% 1/12 • Number of events 1 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	0.00% 0/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	— 0/0 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
Gastrointestinal disorders Colitis (excl infective)	0.00% 0/6 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	8.3% 1/12 • Number of events 1 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	0.00% 0/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	— 0/0 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
Nervous system disorders Seizures and seizure disorder NEC	0.00% 0/6 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	0.00% 0/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	8.3% 1/12 • Number of events 1 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	— 0/0 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.

Other adverse events

Additional Information

Mara L. Becker, MD, MSCE

Duke University

Phone: 919-613-1942

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Fen. SOC+Saline Placebo (Bolus+Infusion) n=6 participants at risk Fentanyl standard of care (SOC) titrated to sedation + saline placebo (bolus + infusion) Fentanyl: Fentanyl standard of care	Fen. SOC+Dex.(.5mcg/kg + .25mcg/kg/hr) n=12 participants at risk Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.2mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.2 mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .5mcg/kg/hr) n=12 participants at risk Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.5mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.5 mcg/kg/hr)	Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) Fentanyl SOC titrated to sedation + Dexmedetomidine (0.5mcg/kg bolus load + 0.7mcg/kg/hr infusion) Fentanyl: Fentanyl standard of care Dexmedetomidine: Dexmedetomidine (0.5 mcg/kg + 0.7 mcg/kg/hr)
Injury, poisoning and procedural complications Anaesthetic and allied procedural complications	0.00% 0/6 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	8.3% 1/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	0.00% 0/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	— 0/0 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
Psychiatric disorders Anxiety symptoms	0.00% 0/6 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	8.3% 1/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	0.00% 0/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	— 0/0 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
Renal and urinary disorders Bladder and urethral symptoms	16.7% 1/6 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	16.7% 2/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	8.3% 1/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	— 0/0 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
Gastrointestinal disorders Colitis (excl infective)	0.00% 0/6 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	8.3% 1/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	0.00% 0/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	— 0/0 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
Respiratory, thoracic and mediastinal disorders Conditions associated with abnormal gas exchange	0.00% 0/6 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	8.3% 1/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	0.00% 0/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	— 0/0 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
Nervous system disorders Encephalopathies NEC	0.00% 0/6 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	8.3% 1/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	0.00% 0/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	— 0/0 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
General disorders Febrile disorders	33.3% 2/6 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	0.00% 0/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	8.3% 1/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	— 0/0 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
General disorders General signs and symptoms NEC	0.00% 0/6 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	8.3% 1/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	0.00% 0/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	— 0/0 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
Investigations Heart rate and pulse investigations	16.7% 1/6 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	0.00% 0/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	0.00% 0/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	— 0/0 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
Hepatobiliary disorders Hepatic failure and associated disorders	0.00% 0/6 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	8.3% 1/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	0.00% 0/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	— 0/0 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
Respiratory, thoracic and mediastinal disorders Laryngeal spasm, oedema and obstruction	16.7% 1/6 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	0.00% 0/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	0.00% 0/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	— 0/0 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
Metabolism and nutrition disorders Magnesium metabolism disorders	0.00% 0/6 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	8.3% 1/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	0.00% 0/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	— 0/0 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
Gastrointestinal disorders Nausea and vomiting symptoms	0.00% 0/6 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	0.00% 0/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	8.3% 1/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	— 0/0 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
Infections and infestations Parainfluenzae viral infections	16.7% 1/6 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	0.00% 0/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	0.00% 0/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	— 0/0 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
Respiratory, thoracic and mediastinal disorders Pneumothorax and pleural effusions NEC	0.00% 0/6 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	8.3% 1/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	8.3% 1/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	— 0/0 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
Metabolism and nutrition disorders Protein metabolism disorders NEC	0.00% 0/6 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	8.3% 1/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	0.00% 0/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	— 0/0 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
Cardiac disorders Rate and rhythm disorders NEC	33.3% 2/6 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	41.7% 5/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	41.7% 5/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	— 0/0 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
Renal and urinary disorders Renal failure and impairment	0.00% 0/6 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	16.7% 2/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	0.00% 0/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	— 0/0 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
Injury, poisoning and procedural complications Respiratory tract and thoracic cavity procedural complications	0.00% 0/6 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	16.7% 2/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	0.00% 0/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	— 0/0 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
Nervous system disorders Seizures and seizure disorders NEC	0.00% 0/6 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	0.00% 0/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	8.3% 1/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	— 0/0 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
Psychiatric disorders Stereotypies and automatisms	0.00% 0/6 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	0.00% 0/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	8.3% 1/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	— 0/0 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
Nervous system disorders Tremor (excl congenital)	0.00% 0/6 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	0.00% 0/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	8.3% 1/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	— 0/0 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.
Vascular disorders Vascular hypotensive disorders	50.0% 3/6 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	50.0% 6/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	41.7% 5/12 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.	— 0/0 • Up to 28 days or until discharge from the ICU (whichever is first) No participants were enrolled in the Fen. SOC+Dex.(.5mcg/kg + .75mcg/kg/hr) group.