Biomarkers of Brain Injury in Critically-Ill Children on Extracorporeal Membrane Oxygenation (BEAM)

The BEAM study is a multicenter, prospective, observational study in children supported on extracorporeal membrane oxygenation (ECMO). The primary goals of this study are to develop and refine a brain injury multimarker panel for accurate neurologic monitoring at the bedside and early classification of mortality and disability outcomes of critically ill children supported on ECMO.

Study Overview

• Status: Active, not recruiting
• Conditions: Extracorporeal Membrane Oxygenation; Children; Neurologic Injury

Detailed Description

The specific aims are to:

1. Determine if circulating levels of brain injury markers during ECMO and brain MRI abnormalities within 6 weeks after ECMO are associated with survival at 18 months after ECMO with a score ≥85 on the Vineland Adaptive Behavior Scales, third edition (VABS-III).
2. Determine whether the presence and degree of inflammation during ECMO and markers of neuroinflammation on brain magnetic resonance spectroscopy (MRS) within 6 weeks after ECMO are associated with survival at 18 months after ECMO with a score ≥85 on VABS-III.
3. Determine whether metabolic and lipid neuroinflammatory pathways will distinguish between at-risk for, acute, and recovery phases of neurologic injury (NI) during ECMO.

• Study Type: Observational
• Enrollment (Estimated): 625

Contacts and Locations

• Study Contact: Name: Melania Bembea, MD, MPH, PhD; Phone Number: 410-955-6412; Email: mbembea1@jhmi.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
  • District of Columbia
    • Washington, District of Columbia, United States, 20310
      • Children's National Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • St. Louis Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Tennessee
    • Memphis, Tennessee, United States, 38163
      • University of Tennessee Health Science Center
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 days to 18 years (Child, Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

225 children who are cannulated onto ECMO and admitted to a pediatric or cardiac Intensive Care Unit at participating institutions.

Description

Inclusion Criteria:

• Children (2 days to <18 years) cannulated onto ECMO and admitted to a pediatric or cardiac Intensive Care Unit at participating institutions.

Exclusion Criteria:

• ECMO cannulation at an outside institution with transport to a study site >24 hours after ECMO initiation
• Limitation of care (e.g., family planning to withdraw support)
• Brain death evaluation within 24 hours of ECMO cannulation
• Inability to speak or understand English or Spanish
• Pregnancy.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Case cohort; Observational study of children between the ages of 2 days to < 18 years who are cannulated onto ECMO at participating sites
Control cohort; Observational study of children between the ages of 2 days to < 18 years admitted to the Johns Hopkins Pediatric Intensive Care Unit (PICU) or Pediatric Cardiac Intensive Care Unit (PCICU) for any reason.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Vineland Adaptive Behavior Scales-Third Edition (VABS-3)	VABS-3 is a 381-item caregiver report measure that was developed to assess adaptive behavior. The questionnaire is divided into 4 domains of adaptive behavior: 1) communication, 2) daily living, 3) social skills and relationships, and 4) physical activity. Each item is rated 0 (never), 1 (sometimes), or 2 (usually or often) as how often the child does the behavior independently without help or reminders. The overall adaptive composite score has a mean of 100 and standard deviation of 15 with lower scores indicating worse intellectual disability.	Baseline and 18 months post-ECMO

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Functional Status Scale (FSS)	The FSS examines 6 domains of functioning: 1) mental status; 2) sensory; 3) communication; 4) motor function; 5) feeding; and 6) respiratory and each domain receives a score of 1 (normal), 2 (mild dysfunction), 3 (moderate dysfunction), 4 (severe dysfunction), or 5 (very severe dysfunction). Final scores range from 6 to 30 with higher scores indicating greater dysfunction.	Baseline and at hospital discharge, up to 18 months post-ECMO
Change in Pediatric Cerebral Performance Category (PCPC)	PCPC consists of a 6-point scale: 1) normal; 2) mild disability; 3) moderate disability; 4) severe disability; 5) coma/vegetative state; 6) brain death. Higher scores indicating worse performance or functional morbidity	Baseline and at hospital discharge, up to 18 months post-ECMO
Change in Pediatric Overall Performance Category (POPC)	POPC consists of a 6-point scale: 1) good overall performance; 2) mild overall disability; 3) moderate overall disability; 4) severe overall disability; 5) coma/vegetative state; 6) brain death. Higher scores indicating worse performance or functional morbidity	Baseline and at hospital discharge, up to 18 months post-ECMO
Change in Pediatric Quality of Life (PedsQL) Inventory	The PedsQL Inventory is a 36-item (for infants 1-12 months), 45 item (for infants 13-24 months) or 23-item (children 2-18) questionnaire with established validity and reliability for health outcomes measurements in pediatric populations, including former PICU patients. The PedsQL is used as a parent proxy report for all ages, as well as self-report in children between 5 and 18 years. The scales are divided into 4 domains of functioning: 1) physical functioning, 2) emotional functioning, 3) social functioning and either 4) cognitive functioning (on the infant scales) or school functioning (on the child scales). Each item on the parent proxy report receives a score of 0 (never), 1 (almost never), 2 (sometimes), 3 (often), or 4 (almost always). Each score on the child report receives a score of 0 (not at all), 2 (sometimes), or 4 (a lot). Final transformed scores range from 0-100 with higher scores indicating better health-related quality of life.	Baseline and 18 months post-ECMO
Consumer Assessment of Healthcare Providers and Systems (CAHPS) Child Survey 5.0H with the Children with Chronic Conditions (CCC) Item Set	The CAHPS CCC is an 81-item questionnaire that provides information on parents' experiences with their child's health care and gives a general indication of how well the health care meets their expectations. Five CCC-specific results are calculated for each population: 1) access to specialized services, 2) family-centered care: personal doctor who knows the child, 3) coordination of care for children with chronic conditions, 4) access to prescription medication, and 5) family-centered care: getting needed information.	18 months post-ECMO

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Melanie Bembea, MD, MPH, PhD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2019
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: August 10, 2021
• First Submitted That Met QC Criteria: September 8, 2021
• First Posted (Actual): September 13, 2021

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Neurodevelopmental Outcomes; Brain Injury Biomarkers
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Wounds and Injuries
• Other Study ID Numbers: IRB00215794; 1R01NS106292 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No