Ignite Creation Date:
2025-12-24 @ 11:17 PM
Ignite Modification Date:
2026-02-27 @ 6:49 AM
Study NCT ID:
NCT05327556
Status:
TERMINATED
Last Update Posted:
2025-08-22
First Post:
2022-04-07
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Epinephrine in the Pediatric Intensive Care Unit: A Dose-Effect Trial
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D007022', 'term': 'Hypotension'}], 'ancestors': [{'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D004837', 'term': 'Epinephrine'}], 'ancestors': [{'id': 'D004983', 'term': 'Ethanolamines'}, {'id': 'D000605', 'term': 'Amino Alcohols'}, {'id': 'D000438', 'term': 'Alcohols'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D000588', 'term': 'Amines'}, {'id': 'D015306', 'term': 'Biogenic Monoamines'}, {'id': 'D001679', 'term': 'Biogenic Amines'}, {'id': 'D002395', 'term': 'Catecholamines'}, {'id': 'D002396', 'term': 'Catechols'}, {'id': 'D010636', 'term': 'Phenols'}, {'id': 'D001555', 'term': 'Benzene Derivatives'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR'], 'maskingDescription': '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.'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 15}}, 'statusModule': {'whyStopped': 'Funding constraints', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2023-02-08', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-08', 'completionDateStruct': {'date': '2025-05-16', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-08-18', 'studyFirstSubmitDate': '2022-04-07', 'studyFirstSubmitQcDate': '2022-04-07', 'lastUpdatePostDateStruct': {'date': '2025-08-22', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2022-04-14', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-05-16', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Incidence of Cardiac Arrest', 'timeFrame': '0 to 120 minutes', 'description': 'The proportion of patients who receive chest compressions at anytime from 0 to 120 minutes after the first dose of study drug'}, {'measure': 'Incidence of Extra-corporeal Membrane Oxygenation (ECMO)', 'timeFrame': '0 to 120 minutes', 'description': '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'}, {'measure': 'Early Survival', 'timeFrame': '7 days', 'description': 'The proportion of patients alive or discharged from the hospital alive at 7 days after the calendar day study drug was administered'}, {'measure': 'Survival to Hospital Discharge', 'timeFrame': '90 days', 'description': 'The proportion of patients alive at time of discharge from the hospital (Truncated at 90 days)'}, {'measure': 'Change in Heart Rate (HR)', 'timeFrame': '10 minutes', 'description': 'Difference in HR before and after PBE is given, using measurements that coincide with the primary outcome'}, {'measure': 'Change in Mean Arterial Pressure (MAP)', 'timeFrame': '10 minutes', 'description': 'Difference in MAP before and after PBE is given, using measurements that coincide with the primary outcome'}, {'measure': 'Change in Diastolic Blood Pressure (DBP)', 'timeFrame': '10 minutes', 'description': 'Difference in DBP before and after PBE is given, using measurements that coincide with the primary outcome'}, {'measure': 'Percent Change in Vital Signs', 'timeFrame': '10 minutes', 'description': 'The difference in SBP, MAP, DBP and HR (defined as above) expressed as a percentage.'}, {'measure': 'Incidence of Stage I Hypertension (or greater)', 'timeFrame': '5 minutes', 'description': '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).'}, {'measure': 'Incidence of Extreme Hypertension', 'timeFrame': '5 minutes', 'description': '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.'}, {'measure': 'Incidence of Non-Responders', 'timeFrame': '10 minutes', 'description': 'The proportion of patients who do not respond to initial dose of study drug, defined as \\<10mmHg difference between nadir and peak SBP'}, {'measure': 'Number of doses of epinephrine per resuscitation episode', 'timeFrame': '120 minutes', 'description': 'Comparison of the number of doses of epinephrine (study drug or open label) given in a discrete resuscitation episode up to 120 minutes after initial dose.'}, {'measure': 'Total dose of epinephrine per resuscitation episode', 'timeFrame': '120 minutes', 'description': 'Comparison of the total dose of epinephrine (study drug or open label) in mcg/kg given in a discrete resuscitation episode up to 120 minutes after initial dose.'}, {'measure': 'Safety Outcomes', 'timeFrame': '0 to 7 days', 'description': 'The proportion of patients who develop the following prespecified safety outcomes:\n\n* Any new arrhythmia within 20 minutes of first dose of study drug\n* Any new arrhythmia requiring intervention within 20 minutes of first dose of study drug\n* 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'}, {'measure': 'Continuous Dose Effect Curve', 'timeFrame': '10 minutes', 'description': 'Correlation of actual dose received in mcg/kg with change in systolic blood pressure.'}, {'measure': 'Effect on change in Systolic Blood Pressure by treatment group', 'timeFrame': '10 minutes', 'description': 'Effect on change in Systolic Blood Pressure by treatment group controlling for:\n\n* Age\n* Nadir BP adjusted for age per PALS handbook (≤28 days of age, SBP \\<60 mmHg; ≥29 days to \\<1 year, SBP \\<70 mmHg; ≥1 year to \\<10 years, SBP \\<70 + 2x(age in years) mmHg; and ≥10 years, SBP \\<90 mmHg.)\n* Provider who was leading the event'}], 'primaryOutcomes': [{'measure': 'Change in Systolic Blood Pressure', 'timeFrame': '10 minutes', 'description': '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.\n\nPrimary 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.'}], 'secondaryOutcomes': [{'measure': 'Incidence of Severe (Stage II) Hypertension', 'timeFrame': '5 minutes', 'description': '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.'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Hypotension']}, 'referencesModule': {'references': [{'pmid': '29526678', 'type': 'BACKGROUND', '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.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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).'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '25 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Male or female less than 26 years of age.\n2. Admitted to BCH and receiving care in a participating ICU.\n3. Is prescribed BDE for acute hypotension deemed to be life-threatening in the judgement of the treating clinician.\n\nExclusion Criteria:\n\n1. Has opted out of the study prior to enrollment.\n2. Has orders in place which limit resuscitation efforts.\n3. Is actively receiving chest compressions while PBE is administered.\n4. Is receiving care in the neonatal intensive care unit.\n5. Is receiving care outside of the ICU at the time PBE is administered (i.e procedural areas).\n6. Is pregnant or breastfeeding.\n7. Is a prisoner.\n8. Is a ward if the state (DCF custody).'}, 'identificationModule': {'nctId': 'NCT05327556', 'acronym': 'EPIDose', 'briefTitle': 'Epinephrine in the Pediatric Intensive Care Unit: A Dose-Effect Trial', 'organization': {'class': 'OTHER', 'fullName': "Boston Children's Hospital"}, 'officialTitle': 'Epinephrine in the Pediatric Intensive Care Unit: A Dose-Effect Trial (EPI Dose)', 'orgStudyIdInfo': {'id': 'P00035730'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': '0.5 mcg/kg Dose', 'description': 'Providers use 0.1 mL/kg of 5 mcg/mL epinephrine for target dose 0.5 mcg/kg', 'interventionNames': ['Drug: Epinephrine 0.5 mcg/kg']}, {'type': 'ACTIVE_COMPARATOR', 'label': '1.0 mcg/kg Dose', 'description': 'Providers use 0.1 mL/kg of 10 mcg/mL epinephrine for target dose of 1.0 mcg/kg', 'interventionNames': ['Drug: Epinephrine 1 mcg/kg']}], 'interventions': [{'name': 'Epinephrine 0.5 mcg/kg', 'type': 'DRUG', 'otherNames': ['Peri-Arrest Bolus Epinephrine'], 'description': 'Syringe with 5 mcg/mL epinephrine', 'armGroupLabels': ['0.5 mcg/kg Dose']}, {'name': 'Epinephrine 1 mcg/kg', 'type': 'DRUG', 'otherNames': ['Peri-Arrest Bolus Epinephrine'], 'description': 'Syringe with 10 mcg/mL epinephrine', 'armGroupLabels': ['1.0 mcg/kg Dose']}]}, 'contactsLocationsModule': {'locations': [{'zip': '02115', 'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'facility': "Boston Children's Hospital", 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}], 'overallOfficials': [{'name': 'Catherine E Ross, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': "Boston Children's Hospital"}]}, 'ipdSharingStatementModule': {'infoTypes': ['STUDY_PROTOCOL', 'SAP', 'ICF', 'CSR', 'ANALYTIC_CODE'], 'timeFrame': 'Immediately following publication of primary results and ending 5 years after publication.', 'ipdSharing': 'YES', 'description': 'All deidentified individual participant data collected during the trial.', 'accessCriteria': '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.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': "Boston Children's Hospital", 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Attending Physician', 'investigatorFullName': 'Catherine E. Ross, MD', 'investigatorAffiliation': "Boston Children's Hospital"}}}}