Trial Outcomes & Findings for Epinephrine in the Pediatric Intensive Care Unit: A Dose-Effect Trial (NCT NCT05327556)

Results Overview

The change in SBP from the nadir SBP prior to study drug administration to the peak SBP after study drug. The nadir SBP was defined as the lowest measurement within the 5 minutes prior to or up to 1 minute after the documented time of study drug. The peak SBP was the highest measurement with 5 minutes following study drug occurring after the nadir SBP. If an additional dose of epinephrine was administered within 5 minutes of the initial dose, the timeframe was truncated so that the peak SBP was the highest value recorded prior to the subsequent epinephrine dose.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

15 participants

Primary outcome timeframe

5 minutes prior to study drug through 5 minutes after study drug

Results posted on

2026-07-07

Participant Flow

Patients meeting eligibility criteria who received study drug between February 8, 2023 to May 16, 2025 at Boston Children's Hospital were enrolled. Given the critical nature of the event of interest, no active recruitment was done.

All enrolled patients completed the study.

Participant milestones

Participant milestones
Measure	1.0 mcg/kg Dose Clinicians were instructed to use 0.1 mL/kg of 10 mcg/mL epinephrine for target dose of 1.0 mcg/kg	0.5 mcg/kg Dose Clinicians were instructed to use 0.1 mL/kg of 5 mcg/mL epinephrine for target dose 0.5 mcg/kg
Overall Study STARTED	6	9
Overall Study COMPLETED	6	9
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Missing data

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1.0 mcg/kg Dose n=6 Participants Clinicians were instructed to use 0.1 mL/kg of 10 mcg/mL epinephrine for target dose of 1.0 mcg/kg	0.5 mcg/kg Dose n=9 Participants Clinicians were instructed to use 0.1 mL/kg of 5 mcg/mL epinephrine for target dose 0.5 mcg/kg	Total n=15 Participants Total of all reporting groups
Age, Continuous	6.4 years n=6 Participants	2.8 years n=9 Participants	2.8 years n=15 Participants
Sex: Female, Male Female	3 Participants n=6 Participants	3 Participants n=9 Participants	6 Participants n=15 Participants
Sex: Female, Male Male	3 Participants n=6 Participants	6 Participants n=9 Participants	9 Participants n=15 Participants
Race/Ethnicity, Customized Hispanic	3 Participants n=6 Participants • Missing data	3 Participants n=7 Participants • Missing data	6 Participants n=13 Participants • Missing data
Race/Ethnicity, Customized Non-Hispanic Asian	0 Participants n=6 Participants • Missing data	1 Participants n=7 Participants • Missing data	1 Participants n=13 Participants • Missing data
Race/Ethnicity, Customized Non-Hispanic Black	2 Participants n=6 Participants • Missing data	1 Participants n=7 Participants • Missing data	3 Participants n=13 Participants • Missing data
Race/Ethnicity, Customized Non-Hispanic White	1 Participants n=6 Participants • Missing data	2 Participants n=7 Participants • Missing data	3 Participants n=13 Participants • Missing data
Nadir SBP Prior to Study Drug	66 mm Hg n=6 Participants • The nadir SBP was defined as the lowest measurement within the 5 minutes prior to or up to 1 minute after the documented time of study drug to allow for minor delays and whole-minute rounding in clinical charting.	66 mm Hg n=9 Participants • The nadir SBP was defined as the lowest measurement within the 5 minutes prior to or up to 1 minute after the documented time of study drug to allow for minor delays and whole-minute rounding in clinical charting.	66 mm Hg n=15 Participants • The nadir SBP was defined as the lowest measurement within the 5 minutes prior to or up to 1 minute after the documented time of study drug to allow for minor delays and whole-minute rounding in clinical charting.

PRIMARY outcome

Timeframe: 5 minutes prior to study drug through 5 minutes after study drug

The change in SBP from the nadir SBP prior to study drug administration to the peak SBP after study drug. The nadir SBP was defined as the lowest measurement within the 5 minutes prior to or up to 1 minute after the documented time of study drug. The peak SBP was the highest measurement with 5 minutes following study drug occurring after the nadir SBP. If an additional dose of epinephrine was administered within 5 minutes of the initial dose, the timeframe was truncated so that the peak SBP was the highest value recorded prior to the subsequent epinephrine dose.

Outcome measures

Outcome measures
Measure	1.0 mcg/kg Dose n=6 Participants Clinicians were instructed to use 0.1 mL/kg of 10 mcg/mL epinephrine for target dose of 1.0 mcg/kg	0.5 mcg/kg Dose n=9 Participants Clinicians were instructed to use 0.1 mL/kg of 5 mcg/mL epinephrine for target dose 0.5 mcg/kg
Change in Systolic Blood Pressure	48 mmHg Interval 46.0 to 150.0	40 mmHg Interval 9.0 to 58.0

SECONDARY outcome

Timeframe: 5 minutes after study drug

The proportion of patients whose peak systolic blood pressure (determined as per the primary outcome) is greater than or equal to the 95th percentile plus 12 mmHg or greater than or equal to 140 mmHg, whichever is lower.

Outcome measures

Outcome measures
Measure	1.0 mcg/kg Dose n=6 Participants Clinicians were instructed to use 0.1 mL/kg of 10 mcg/mL epinephrine for target dose of 1.0 mcg/kg	0.5 mcg/kg Dose n=9 Participants Clinicians were instructed to use 0.1 mL/kg of 5 mcg/mL epinephrine for target dose 0.5 mcg/kg
Incidence of Severe (Stage II) Hypertension	4 Participants	2 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 0 to 120 minutes after study drug

The proportion of patients who receive chest compressions at anytime from 0 to 120 minutes after the first dose of study drug

Outcome measures

Outcome measures
Measure	1.0 mcg/kg Dose n=6 Participants Clinicians were instructed to use 0.1 mL/kg of 10 mcg/mL epinephrine for target dose of 1.0 mcg/kg	0.5 mcg/kg Dose n=9 Participants Clinicians were instructed to use 0.1 mL/kg of 5 mcg/mL epinephrine for target dose 0.5 mcg/kg
Incidence of Cardiac Arrest	0 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 0 to 120 minutes after study drug

The proportion of patients who are cannulated to ECMO at anytime from 0 to 120 minutes after the first dose of study drug, starting at time of first flow

Outcome measures

Outcome measures
Measure	1.0 mcg/kg Dose n=6 Participants Clinicians were instructed to use 0.1 mL/kg of 10 mcg/mL epinephrine for target dose of 1.0 mcg/kg	0.5 mcg/kg Dose n=9 Participants Clinicians were instructed to use 0.1 mL/kg of 5 mcg/mL epinephrine for target dose 0.5 mcg/kg
Incidence of Extra-corporeal Membrane Oxygenation (ECMO)	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: through 120 minutes after study drug

The proportion of patients alive 120 minutes after study drug was administered.

Outcome measures

Outcome measures
Measure	1.0 mcg/kg Dose n=6 Participants Clinicians were instructed to use 0.1 mL/kg of 10 mcg/mL epinephrine for target dose of 1.0 mcg/kg	0.5 mcg/kg Dose n=9 Participants Clinicians were instructed to use 0.1 mL/kg of 5 mcg/mL epinephrine for target dose 0.5 mcg/kg
Event Survival	6 Participants	9 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: through hospital discharge, truncated at 90 days

The proportion of patients alive at time of discharge from the hospital (Truncated at 90 days)

Outcome measures

Outcome measures
Measure	1.0 mcg/kg Dose n=6 Participants Clinicians were instructed to use 0.1 mL/kg of 10 mcg/mL epinephrine for target dose of 1.0 mcg/kg	0.5 mcg/kg Dose n=9 Participants Clinicians were instructed to use 0.1 mL/kg of 5 mcg/mL epinephrine for target dose 0.5 mcg/kg
Survival to Hospital Discharge	3 Participants	5 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 5 minutes prior to study drug through 5 minutes after study drug

The change in HR from the nadir HR prior to study drug administration to the peak HR after study drug. The nadir HR was defined as the lowest measurement within the 5 minutes prior to or up to 1 minute after the documented time of study drug. The peak HR was the highest measurement with 5 minutes following study drug occurring after the nadir HR. If an additional dose of epinephrine was administered within 5 minutes of the initial dose, the timeframe was truncated so that the peak HR was the highest value recorded prior to the subsequent epinephrine dose.

Outcome measures

Outcome measures
Measure	1.0 mcg/kg Dose n=6 Participants Clinicians were instructed to use 0.1 mL/kg of 10 mcg/mL epinephrine for target dose of 1.0 mcg/kg	0.5 mcg/kg Dose n=9 Participants Clinicians were instructed to use 0.1 mL/kg of 5 mcg/mL epinephrine for target dose 0.5 mcg/kg
Change in Heart Rate (HR)	16 beats per minute Interval 6.0 to 40.0	19 beats per minute Interval 11.0 to 35.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 5 minutes prior to study drug through 5 minutes after study drug

Difference in MAP within 5 minutes before and after study drug using measurements corresponding with the nadir and peak SBP (primary outcome).

Outcome measures

Outcome measures
Measure	1.0 mcg/kg Dose n=6 Participants Clinicians were instructed to use 0.1 mL/kg of 10 mcg/mL epinephrine for target dose of 1.0 mcg/kg	0.5 mcg/kg Dose n=9 Participants Clinicians were instructed to use 0.1 mL/kg of 5 mcg/mL epinephrine for target dose 0.5 mcg/kg
Change in Mean Arterial Pressure (MAP)	32 mmHg Interval 25.0 to 112.0	25 mmHg Interval 17.0 to 39.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 5 minutes before study drug through 5 minutes after study drug

Difference in DBP within 5 minutes before and after study drug using measurements corresponding with the nadir and peak SBP (primary outcome).

Outcome measures

Outcome measures
Measure	1.0 mcg/kg Dose n=6 Participants Clinicians were instructed to use 0.1 mL/kg of 10 mcg/mL epinephrine for target dose of 1.0 mcg/kg	0.5 mcg/kg Dose n=9 Participants Clinicians were instructed to use 0.1 mL/kg of 5 mcg/mL epinephrine for target dose 0.5 mcg/kg
Change in Diastolic Blood Pressure (DBP)	25 mmHg Interval 17.0 to 82.0	21 mmHg Interval 13.0 to 32.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 5 minutes before study drug through 5 minutes after study drug

The difference in SBP before and after study drug as defined by the primary outcome, expressed as a percentage. This was calculated by dividing the change in SBP (peak SBP minus nadir SBP) by the nadir SBP.

Outcome measures

Outcome measures
Measure	1.0 mcg/kg Dose n=6 Participants Clinicians were instructed to use 0.1 mL/kg of 10 mcg/mL epinephrine for target dose of 1.0 mcg/kg	0.5 mcg/kg Dose n=9 Participants Clinicians were instructed to use 0.1 mL/kg of 5 mcg/mL epinephrine for target dose 0.5 mcg/kg
Percent Change in SBP	80 percent change Interval 59.0 to 224.0	62 percent change Interval 43.0 to 79.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 5 minutes after study drug

The proportion of patients whose peak systolic blood pressure (as per the primary outcome) is greater than or equal to the 95th percentile or 130/80 mm Hg (whichever is lower).

Outcome measures

Outcome measures
Measure	1.0 mcg/kg Dose n=6 Participants Clinicians were instructed to use 0.1 mL/kg of 10 mcg/mL epinephrine for target dose of 1.0 mcg/kg	0.5 mcg/kg Dose n=9 Participants Clinicians were instructed to use 0.1 mL/kg of 5 mcg/mL epinephrine for target dose 0.5 mcg/kg
Incidence of Stage I Hypertension (or Greater)	4 Participants	5 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 5 minutes after study drug

The proportion of patients whose peak systolic blood pressure (as per the primary outcome) is greater than or equal to the 95th percentile + 30 mm Hg or ≥170, whichever is lower.

Outcome measures

Outcome measures
Measure	1.0 mcg/kg Dose n=6 Participants Clinicians were instructed to use 0.1 mL/kg of 10 mcg/mL epinephrine for target dose of 1.0 mcg/kg	0.5 mcg/kg Dose n=9 Participants Clinicians were instructed to use 0.1 mL/kg of 5 mcg/mL epinephrine for target dose 0.5 mcg/kg
Incidence of Extreme Hypertension	3 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 5 minutes before study drug through 5 minutes after study drug

The proportion of patients who do not respond to initial dose of study drug, defined as \<10mmHg difference between nadir and peak SBP

Outcome measures

Outcome measures
Measure	1.0 mcg/kg Dose n=6 Participants Clinicians were instructed to use 0.1 mL/kg of 10 mcg/mL epinephrine for target dose of 1.0 mcg/kg	0.5 mcg/kg Dose n=9 Participants Clinicians were instructed to use 0.1 mL/kg of 5 mcg/mL epinephrine for target dose 0.5 mcg/kg
Incidence of Non-Responders	0 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 1 to 120 minutes after study drug

Comparison of the proportion of patients requiring 1 or more additional doses of epinephrine (study drug or open label) given in a discrete resuscitation episode up to 120 minutes after initial dose.

Outcome measures

Outcome measures
Measure	1.0 mcg/kg Dose n=6 Participants Clinicians were instructed to use 0.1 mL/kg of 10 mcg/mL epinephrine for target dose of 1.0 mcg/kg	0.5 mcg/kg Dose n=9 Participants Clinicians were instructed to use 0.1 mL/kg of 5 mcg/mL epinephrine for target dose 0.5 mcg/kg
Proportion of Patients Requiring 1 or More Additional Doses of Epinephrine	1 Participants	6 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 0 to 120 minutes after study drug

Comparison of the cumulative dose of epinephrine (study drug or open label) in mcg/kg given in a discrete resuscitation episode up to 120 minutes after initial dose.

Outcome measures

Outcome measures
Measure	1.0 mcg/kg Dose n=6 Participants Clinicians were instructed to use 0.1 mL/kg of 10 mcg/mL epinephrine for target dose of 1.0 mcg/kg	0.5 mcg/kg Dose n=9 Participants Clinicians were instructed to use 0.1 mL/kg of 5 mcg/mL epinephrine for target dose 0.5 mcg/kg
Cumulative Dose of Epinephrine Per Resuscitation Episode	1.04 mcg/kg Interval 1.0 to 1.09	0.52 mcg/kg Interval 0.32 to 1.58

OTHER_PRE_SPECIFIED outcome

Timeframe: 0 to 7 days after study drug

The proportion of patients who develop any the following prespecified safety outcomes (composite): * Any new arrhythmia within 20 minutes of first dose of study drug * Any new arrhythmia requiring intervention within 20 minutes of first dose of study drug * Intracranial hemorrhage associated with severe or extreme hypertension within 5 minutes of the first dose of study drug which is diagnosed within 7 days after the calendar day study drug was administered

Outcome measures

Outcome measures
Measure	1.0 mcg/kg Dose n=6 Participants Clinicians were instructed to use 0.1 mL/kg of 10 mcg/mL epinephrine for target dose of 1.0 mcg/kg	0.5 mcg/kg Dose n=9 Participants Clinicians were instructed to use 0.1 mL/kg of 5 mcg/mL epinephrine for target dose 0.5 mcg/kg
Safety Outcomes -- Composite	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 5 minutes prior to study drug through 5 minutes after study drug

Correlation of actual dose received in mcg/kg with change in systolic blood pressure.

Outcome measures

Outcome measures
Measure	1.0 mcg/kg Dose n=15 Participants Clinicians were instructed to use 0.1 mL/kg of 10 mcg/mL epinephrine for target dose of 1.0 mcg/kg	0.5 mcg/kg Dose Clinicians were instructed to use 0.1 mL/kg of 5 mcg/mL epinephrine for target dose 0.5 mcg/kg
Correlation of Dose and SBP Response (Continuous)	0.44 correlation coefficient	—

Adverse Events

1.0 mcg/kg Dose

Serious events: 0 serious events

Other events: 0 other events

Deaths: 3 deaths

0.5 mcg/kg Dose

Serious events: 0 serious events

Other events: 0 other events

Deaths: 4 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Catherine Ross, MD

Boston Children's Hospital

Phone: 617-355-6000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place