Epinephrine in the Pediatric Intensive Care Unit: A Dose-Effect Trial

NCT05327556 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: P00035730
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypotension

Outcome Measures

Primary Outcomes (1)

• Change in Systolic Blood Pressure

  The lowest systolic blood pressure value in the 5 minutes prior to or up to 1 minute after the documented time of PBE administration (nadir) subtracted from the highest systolic blood pressure in the 5 minutes following PBE (must be subsequent to the nadir). If an additional dose of PBE was administered within 5 minutes of the initial dose, the peak SBP will be the highest value recorded prior to the subsequent dose. Primary analysis will be performed with an intention-to-treat approach based on the concentration of study drug received. An exploratory analysis will be performed per protocol based on the actual volume of study drug the patient received on first administration being within 20% of the intended volume. Patients who received ≥0.4 to ≤0.6 mcg/kg will be considered in the 0.5 mcg/kg group whereas patients who received ≥0.8 to ≤1.2 mcg/kg will be considered in the 1 mcg/kg group.

  10 minutes

Secondary Outcomes (1)

• Incidence of Severe (Stage II) Hypertension

  5 minutes

Other Outcomes (16)

• Incidence of Cardiac Arrest

  0 to 120 minutes

• Incidence of Extra-corporeal Membrane Oxygenation (ECMO)

  0 to 120 minutes

• Early Survival

  7 days

Study Arms (2)

0.5 mcg/kg Dose

ACTIVE COMPARATOR

Providers use 0.1 mL/kg of 5 mcg/mL epinephrine for target dose 0.5 mcg/kg

Drug: Epinephrine 0.5 mcg/kg

1.0 mcg/kg Dose

ACTIVE COMPARATOR

Providers use 0.1 mL/kg of 10 mcg/mL epinephrine for target dose of 1.0 mcg/kg

Drug: Epinephrine 1 mcg/kg

Interventions

Epinephrine 0.5 mcg/kg DRUG

Syringe with 5 mcg/mL epinephrine

Also known as: Peri-Arrest Bolus Epinephrine

0.5 mcg/kg Dose

Epinephrine 1 mcg/kg DRUG

Syringe with 10 mcg/mL epinephrine

Also known as: Peri-Arrest Bolus Epinephrine

1.0 mcg/kg Dose

Eligibility Criteria

• Age: Up to 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Boston Children's Hospital: lead

Study Sites (1)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• 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.

  PMID: 29526678 BACKGROUND

MeSH Terms

Conditions

Hypotension

Interventions

Epinephrine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Catherine E Ross, MD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Study kits in either arm will be identical, and only the research pharmacy and the study statisticians will have access to the populated Master Randomization List.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending Physician

Study Record Dates

• First Submitted: April 7, 2022
• First Posted: April 14, 2022
• Study Start: February 8, 2023
• Primary Completion: May 16, 2025
• Study Completion: May 16, 2025
• Last Updated: May 13, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Immediately following publication of primary results and ending 5 years after publication.
• Access Criteria: Data will be made available on a case by case basis to investigators whose proposed use of the data has been approved by the primary investigator.

Locations

US (1)