Clinical trial NCT05327556: Epinephrine in the Pediatric Intensive Care Unit: A Dose-Effect Trial
Official title: Epinephrine in the Pediatric Intensive Care Unit: A Dose-Effect Trial (EPI Dose)
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE2
Conditions: Hypotension
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
First posted: 2022-04-14
Enrollment: 86
Sex: ALL
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The use of peri-arrest bolus epinephrine (PBE) has emerged as a rescue strategy for life-threatening hypotension in pediatric intensive care units (ICU) despite scant published data supporting its use in this setting. As optimal dosing of PBE in this population is unclear, we aim to determine if an initial dose of 0.5 mcg/kg versus 1.0 mcg/kg yields differences in hemodynamic outcomes. The EPI Dose Study is a single-center, prospective, randomized, double-blind, dose-effect trial measuring systolic blood pressure (SBP) before and after PBE is given. We hypothesize that the 1.0 mcg/kg group will have more robust increases in SBP.

Detailed description: In order to test the hypothesis that PBE doses of 1.0 mcg/kg will have more robust increases in SBP as compared to 0.5 mcg/kg in critically ill children and young adults with acute hypotension, we plan to conduct a Phase II, single-center, prospective, randomized, double-blind, dose-effect trial. Children and young adults \<26 years of age who, at the discretion of the clinical team, require rescue PBE for life-threatening hypotension and meet inclusion/exclusion criteria will be enrolled. Prior to randomization, our pharmacy team will prepare treatment packets with 3 pre-mixed PBE which will be stocked in the ICUs with either 5 mcg/mL or 10 mcg/mL of epinephrine. Clinicians will be instructed to use 0.1 mL/kg of the experimental syringe for the initial dose, resulting in target doses of 0.5 mcg/kg (Arm 1) or 1 mcg/kg (Arm 2), respectively. Treatment packs will be labeled according to the randomization scheme, and only the pharmacy team will have knowledge of the concentration of epinephrine in each package. Nurses will be instructed to record the exact time of the experimental dose, around which all time-sensitive data will be collected. The clinicians, patients and research team will be blinded to the intervention. We will not restrict any other interventions chosen by the clinical team. Unblinded interim analyses will be performed after the first 6 months of enrollment, and every 12 months thereafter through study completion and reported to the Data and Safety Monitoring Board (DSMB).

Eligibility criteria: Inclusion Criteria:

1. Male or female less than 26 years of age.
2. Admitted to BCH and receiving care in a participating ICU.
3. Is prescribed BDE for acute hypotension deemed to be life-threatening in the judgement of the treating clinician.

Exclusion Criteria:

1. Has opted out of the study prior to enrollment.
2. Has orders in place which limit resuscitation efforts.
3. Is actively receiving chest compressions while PBE is administered.
4. Is receiving care in the neonatal intensive care unit.
5. Is receiving care outside of the ICU at the time PBE is administered (i.e procedural areas).
6. Is pregnant or breastfeeding.
7. Is a prisoner.
8. Is a ward if the state (DCF custody).

Primary outcomes:
measure: Change in Systolic Blood Pressure
timeFrame: 10 minutes
Secondary outcomes:
measure: Incidence of Severe (Stage II) Hypertension
timeFrame: 5 minutes
Other outcomes:
measure: Incidence of Cardiac Arrest
timeFrame: 0 to 120 minutes
measure: Incidence of Extra-corporeal Membrane Oxygenation (ECMO)
timeFrame: 0 to 120 minutes
measure: Early Survival
timeFrame: 7 days
measure: Survival to Hospital Discharge
timeFrame: 90 days
measure: Change in Heart Rate (HR)
timeFrame: 10 minutes
measure: Change in Mean Arterial Pressure (MAP)
timeFrame: 10 minutes
measure: Change in Diastolic Blood Pressure (DBP)
timeFrame: 10 minutes
measure: Percent Change in Vital Signs
timeFrame: 10 minutes
measure: Incidence of Stage I Hypertension (or greater)
timeFrame: 5 minutes
measure: Incidence of Extreme Hypertension
timeFrame: 5 minutes
measure: Incidence of Non-Responders
timeFrame: 10 minutes
measure: Number of doses of epinephrine per resuscitation episode
timeFrame: 120 minutes
measure: Total dose of epinephrine per resuscitation episode
timeFrame: 120 minutes
measure: Safety Outcomes
timeFrame: 0 to 7 days
measure: Continuous Dose Effect Curve
timeFrame: 10 minutes
measure: Effect on change in Systolic Blood Pressure by treatment group
timeFrame: 10 minutes
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
Study officials:
affiliation: Boston Children's Hospital
name: Catherine E Ross, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ross CE, Asaro LA, Wypij D, Holland CC, Donnino MW, Kleinman ME. Physiologic response to pre-arrest bolus dilute epinephrine in the pediatric intensive care unit. Resuscitation. 2018 May;126:137-142. doi: 10.1016/j.resuscitation.2018.03.011. Epub 2018 Mar 8.