MedPath

ARDS in Children and ECMO Initiation Strategies Impact on Neurodevelopment (ASCEND)

Recruiting
Conditions
Acute Respiratory Distress Syndrome
Extracorporeal Membrane Oxygenation
Interventions
Device: ECMO support
Other: PROSpect protocolized therapies
Registration Number
NCT05388708
Lead Sponsor
University of Michigan
Brief Summary

ASCEND researchers are partnering with families of children who receive extracorporeal membrane oxygenation (ECMO) after a sudden failure of breathing named pediatric acute respiratory distress syndrome (PARDS). ECMO is a life support technology that uses an artificial lung outside of the body to do the lung's work. ASCEND has two objectives.

The first objective is to learn more about children's abilities and quality of life among ECMO-supported children in the year after they leave the pediatric intensive care unit. The second objective is to compare short and long-term patient outcomes in two groups of children: one group managed with a mechanical ventilation protocol that reserves the use of extracorporeal membrane oxygenation (ECMO) until protocol failure to another group supported on ECMO per usual care.

Detailed Description

Decades after extracorporeal membrane oxygenation (ECMO) was first used to support children with severe pediatric acute respiratory distress syndrome (PARDS), pediatric intensivists lack both prospective studies of long-term outcomes in ECMO for PARDS and well-powered studies comparing the impact of ECMO initiation strategies on mortality and morbidity. While clinicians lack the equipoise necessary to randomize ECMO in dying children, there is uncertainty on if and when it is best to initiate ECMO to preserve survival, functioning, and quality of life. To determine if and when ECMO should be initiated in children with severe PARDS, it is necessary to compare the long-term outcomes in ECMO supported children to otherwise similar children who did not receive ECMO at the same threshold if at all.

An opportunity to address this question is provided by NHLBI-funded Prone and Oscillation Pediatric Clinical Trial (PROSpect) and the ECMO registry, Extracorporeal Life Support Organization (ELSO). PROSpect is an existing randomized clinical trial testing the impact of supine/prone positioning and conventional mechanical ventilation/high-frequency oscillatory ventilation on short and long-term clinical outcomes in 1,000 children with severe PARDS. PROSpect manages subjects with a rigorous protocol that reserves ECMO for protocol failure. The ELSO Registry includes children receiving usual care ECMO, initiated at the discretion of the intensivist.

ASCEND harmonizes PROSpect and ELSO data collection and prospectively measures functional status and quality of life via surveys in an additional 550 children with severe PARDS from ELSO sites. ASCEND measures children's abilities and quality of life when the child was in their normal state of health (just prior to being hospitalized), at discharge from the pediatric intensive care unit, and at 1-month, 3-months, 6-months, and 12-months after discharge from the pediatric intensive care unit. After enrollment of the usual care ECMO (in ELSO) and PROSpect's protocolized therapies (from the PROSpect clinical trial) is complete, then ASCEND will match similarly critically ill children based on their propensity to receive usual care ECMO.

ASCEND combines real-world observational data (from ELSO) and a randomized clinical trial (from PROSpect) to address two specific aims.

Aim 1: The study will test the hypotheses that one year after children receive usual care ECMO for PARDS, there will be a decline in long-term functional status and health-related quality of life as well as an increase in the proportion of children receiving respiratory support.

Aim 2: The study will test the hypotheses that 90-day mortality, one-year functional status, and one-year health-related quality of life are not equivalent for children with usual care ECMO (in ELSO) and PROSpect's protocolized therapies.

Protocol change in November 2021:

Inclusion criteria: Extend the window between intubation and ECMO cannulation from 120 hours to 168 hours.

Exclusion criteria: Remove active air leak, critical airway, and facial surgery/trauma within the last 2 weeks.

Protocol change in October 2022:

Inclusion criteria:

1. Extended the age range from 14 days - 17 years to 14 days - 20 years of age.

2. Extended the window between intubation and ECMO cannulation from 168 hours to 240 hours.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
550
Inclusion Criteria
  • Time between intubation and ECMO cannulation is less than 240 hours (10 days)
  • ECMO support type is respiratory (VV or VA cannulation)
  • Chest radiograph with bilateral lung disease
  • Moderate or severe pediatric ARDS as measured by oxygenation index or oxygen saturation index after intubation and prior to ECMO cannulation:

One OI ≥ 16 or Two OIs ≥ 12 and ≤ 16 at least four hours apart or Two OSIs ≥ 10 at least four hours apart or One OI ≥ 12 and ≤ 16 and One OSI ≥ 10 at least four hours apart

Exclusion Criteria
  • Previously enrolled in PROSpect
  • Perinatal related lung disease
  • Congenital diaphragmatic hernia or congenital/acquired diaphragm paralysis
  • Respiratory failure caused by cardiac failure or fluid overload
  • Cyanotic congenital heart disease
  • Cardiomyopathy
  • Primary pulmonary hypertension (PAH)
  • Unilateral lung disease
  • Intubated for status asthmaticus
  • Obstructive airway disease
  • Bronchiolitis obliterans
  • Post hematopoietic stem cell transplant
  • Post lung transplant
  • Home ventilator dependent
  • Neuromuscular respiratory failure
  • Head trauma: (managed with hyperventilation)
  • Intracranial bleeding
  • Unstable spine, femur or pelvic fractures
  • Acute abdominal process/open abdomen
  • Family/medical team have decided to not provide full support
  • Enrolled in interventional clinical trial: not approved for co-enrollment; does not include cancer protocols.
  • Known pregnancy

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Usual care ECMO CohortECMO supportThe cohort will be comprised of 550 patients, aged 14 days to 20 years, who go on extracorporeal membrane oxygenation (ECMO) support due to pediatric acute respiratory distress syndrome (PARDS) at physician discretion. Patients with qualifying PARDS must have one oxygenation index (OI) ≥ 16 or two OIs 12 ≥ to \< 16 (at least 4 hours apart) or two oxygenation saturation indexes (OSIs) ≥ 10 (at least 4 hours apart) or one OI 12 ≥ to \< 16 and one OSI \> 10 (at least 4 hours apart) Subjects must be on mechanical ventilation for less than 240 hours (10 days) prior to cannulation. These measures must be after endotracheal intubation and before ECMO start. Chest radiograph prior to ECMO must show bilateral lung disease. Subjects cannulated on ECMO for no more than 96 hours prior to gaining consent.
PROSpect protocolized therapies cohortPROSpect protocolized therapiesThe cohort will be comprised of 1000 patients, aged 14 days to 20 years, who are endotracheally intubated for PARDS. Patients with qualifying PARDS must have one oxygenation index (OI) ≥ 16 or two OIs 12 ≥ to \< 16 (at least 4 hours apart) or two oxygenation saturation indexes (OSIs) ≥ 10 (at least 4 hours apart) or one OI 12 ≥ to \< 16 and one OSI \> 10 (at least 4 hours apart). These measures must be after endotracheal intubation. Chest radiograph must show bilateral lung disease. Patient must be enrolled in a clinical trial Prone and Oscillation Pediatric Clinical Trial (PROSpect) NCT01515787 which is distinct from ASCEND. PROSpect is a response adaptive randomized clinical trial, testing the impact of supine/prone positioning and conventional mechanical ventilation/high-frequency oscillatory ventilation on short and long-term clinical outcomes in children with severe PARDS. PROSpect manages severe PARDS subjects using a rigorous protocol that reserves ECMO for protocol failure.
Primary Outcome Measures
NameTimeMethod
Comparative change in one-year functional statusbaseline and 1 year after pediatric intensive care unit discharge

This primary comparative long-term outcome is measured among both usual care ECMO and PROSpect protocolized therapy groups. The outcome compares the change in the functional status as measured at baseline and 12 months after PICU discharge between matched children in the two groups. The instrument is the functional status scale score.

The Functional Status Scale (FSS) is a valid and reliable assessment method to quantify functional status. The FSS includes 6 domains: mental status, sensory functioning, communication, motor function, feeding, and respiratory. Scores for each domain range from 1 (normal) to 5 (very severe dysfunction); total scores range from 6 to 30 with higher scores reflecting worse functioning.

Change in health-related quality of lifebaseline and 1 year after pediatric intensive care unit discharge

This primary natural history outcome is measured among usual care ECMO patients. This outcome is the change in the health-related quality of life as measured at baseline and 12 months after PICU discharge. The instrument is the age-appropriate Version 4.0 Pediatric Quality of Life Inventory (PedsQL 4.0) generic core scales for acute illness.

PedsQL 4.0 Generic Core Scales and Infant Scales - Acute Version are parent proxy-report scales. The scales ranges from 0 to 100, with higher scores indicating fewer problems. PedsQL 4.0 Generic Core Scales is a 23-item scale with 4 domains: physical functioning, emotional functioning, social functioning, and school functioning. The PedsQL Infant Scales consist of 36-45 questions, depending on age, with 5 domains: physical functioning, physical symptoms, emotional functioning, social functioning, and cognitive functioning.

Change in functional statusbaseline and 1 year after pediatric intensive care unit discharge

This primary natural history outcome is measured among usual care extracorporeal membrane oxygenation (ECMO) patients. This outcome is the change in functional status as measured at baseline and 12 months after pediatric intensive care unit (PICU) discharge. The instrument is the functional status scale score. The baseline measure will be made within 96 hours of ECMO initiation and reflect patient's status in the week prior to ECMO.

The Functional Status Scale (FSS) is a valid and reliable assessment method to quantify functional status. The FSS includes 6 domains: mental status, sensory functioning, communication, motor function, feeding, and respiratory. Scores for each domain range from 1 (normal) to 5 (very severe dysfunction); total scores range from 6 to 30 with higher scores reflecting worse functioning.

The proportion of children with a new morbiditybaseline and 1 year after pediatric intensive care unit discharge

This primary natural history outcome is measured among usual care ECMO patients. A new morbidity is defined as a change in the functional status scale score instrument by 3 or more, as previously described. This outcome will report the proportion of children who acquire a new morbidity as measured at baseline and 12 months after PICU discharge.

The Functional Status Scale (FSS) is a valid and reliable assessment method to quantify functional status. The FSS includes 6 domains: mental status, sensory functioning, communication, motor function, feeding, and respiratory. Scores for each domain range from 1 (normal) to 5 (very severe dysfunction); total scores range from 6 to 30 with higher scores reflecting worse functioning.

All-cause mortality at hospital discharge or 90-days90 days after the day of illness on which patients from the two cohorts are matched

This primary comparative short-term outcome is measured among both usual care ECMO and Prone and Oscillation Pediatric Clinical Trial (PROSpect) protocolized therapy groups. The outcome compares the 90-day mortality for matched children in the two groups. The endpoint is 90 days after the day of illness on which patients from the two cohorts are matched or hospital discharge.

Comparative change in one-year health-related quality of lifebaseline and 1 year after pediatric intensive care unit discharge

This primary comparative long-term outcome is measured among both usual care ECMO and PROSpect protocolized therapy groups. The outcome compares the change in the health-related quality of life as measured at baseline and 12 months after PICU discharge between matched children in the two groups. The instrument is the change in the age-appropriate PedsQL 4.0 generic core scales for acute illness.

PedsQL 4.0 Generic Core Scales and Infant Scales - Acute Version are parent proxy-report scales. The scales ranges from 0 to 100, with higher scores indicating fewer problems. PedsQL 4.0 Generic Core Scales is a 23-item scale with 4 domains: physical functioning, emotional functioning, social functioning, and school functioning. The PedsQL Infant Scales consist of 36-45 questions, depending on age, with 5 domains: physical functioning, physical symptoms, emotional functioning, social functioning, and cognitive functioning.

Secondary Outcome Measures
NameTimeMethod
Change in breathing supportbaseline and 1 year after pediatric intensive care unit discharge

This secondary natural history outcome is measured among usual care ECMO patients. This outcome is the change in breathing support measured at baseline and 12 months after PICU discharge. The instrument is the respiratory subscale of the functional status scale score.

The Functional Status Scale (FSS) is a valid and reliable assessment method to quantify functional status with 6 domains. This measure of breathing support will rely on the FSS respiratory domain. The respiratory domain score ranges from 1 (normal) to 5 (very severe dysfunction).

Change in the physical component of health-related quality of lifebaseline and 1 year after pediatric intensive care unit discharge

This secondary natural history outcome is measured among usual care ECMO patients. The outcome is the change in the physical component of health-related quality of life measured at baseline and 12 months after PICU discharge. The instrument is the age-appropriate physical health summary score of the PedsQL 4.0 generic core scales for acute illness.

PedsQL 4.0 Generic Core Scales and Infant Scales - Acute Version are parent proxy-report scales. The scales range from 0 to 100, with higher scores indicating fewer problems. The physical component of the PedsQL 4.0 Generic Core Scales is composed of one of the four domains: physical functioning. The PedsQL Infant Scales physical component is composed of two of the five domains: physical functioning and physical symptoms.

Change in family impact of the child's healthbaseline and 1 year after pediatric intensive care unit discharge

This secondary natural history outcome is measured among usual care ECMO patients. This outcome is the change in child fatigue measured at baseline and 12 months after PICU discharge. The instrument is the age-appropriate PedsQL fatigue scale for acute illness.

The PedsQL™ Family Impact Module - Acute Version is a 36-item scale that encompasses eight domains: Physical Functioning, Emotional Functioning, Social Functioning, Cognitive Functioning, Communication, Worry, Daily Activities, and Family Relationships. The scale ranges from 0 to 100, with higher scores indicating fewer problems.

Difference between groups in intracranial bleeding or ischemic stroke28 days after day in illness patients are matched or during hospitalization

This secondary comparative short-term outcome is measured among both usual care ECMO and PROSpect protocolized therapy groups. This outcome compares the difference in the proportion of matched children who suffer a new intracranial hemorrhage or ischemic stroke (recognized on radiologic imaging) between the two groups.

Change in pediatric overall performance categorybaseline and 1 year after pediatric intensive care unit discharge

This secondary natural history outcome is measured among usual care ECMO patients. The outcome is the change in the pediatric overall performance category measured at baseline and 12 months after PICU discharge. The instrument is the pediatric overall performance category.

The Pediatric Overall Performance Category (POPC) quantifies impairments and functional morbidity. Scores range from 1 to 6 with 1: good, 2: mild disability, 3: moderate disability, 4: severe disability, 5: coma, and 6: brain death.

Change in pediatric cerebral performance categorybaseline and 1 year after pediatric intensive care unit discharge

This secondary natural history outcome is measured among usual care ECMO patients. This outcome is the change in the pediatric cerebral performance category measured at baseline and 12 months after PICU discharge. The instrument is the pediatric cerebral performance category.

The Pediatric Cerebral Performance Category (PCPC) quantifies cognitive impairments. Scores range from 1 to 6 with 1: good, 2: mild disability, 3: moderate disability, 4: severe disability, 5: coma, and 6: brain death.

Change in child fatiguebaseline and 1 year after pediatric intensive care unit discharge

This secondary natural history outcome is measured among usual care ECMO patients. This outcome is the change in child fatigue measured at baseline and 12 months after PICU discharge. The instrument is the age-appropriate PedsQL fatigue scale for acute illness.

The PedsQL™ Multi-dimensional Fatigue Scale - Acute Version is an 18-item scale that encompasses three domains: General Fatigue, Sleep/Rest Fatigue and Cognitive Fatigue. The scale ranges from 0 to 100, with higher scores indicating fewer problems and better health-related quality of life.

Change in the psychosocial component of health-related quality of lifebaseline and 1 year after pediatric intensive care unit discharge

This secondary natural history outcome is measured among usual care ECMO patients. This outcome is the change in the psychosocial component of health-related quality of life measured at baseline and 12 months after PICU discharge. The instrument is the age-appropriate psychosocial health summary score of the PedsQL 4.0 generic core scales for acute illness.

PedsQL 4.0 Generic Core Scales and Infant Scales - Acute Version are parent proxy-report scales. The scales range from 0 to 100, with higher scores indicating fewer problems. The psychosocial component of the PedsQL 4.0 Generic Core Scales is composed of three of the four domains: emotional functioning, social functioning, and school functioning. The PedsQL Infant Scales psychosocial component is composed of three of the five domains: emotional functioning, social functioning, and cognitive functioning.

Change in one-year functional status of children suffering a neurologic injurybaseline and 1 year after pediatric intensive care unit discharge

This secondary natural history outcome is measured among usual care ECMO patients. A neurologic injury is defined as a new intracranial hemorrhage or stroke recognized on radiologic imaging. This outcome will compare the change in functional status as measured at baseline and 12 months after PICU discharge between those children who suffered a neurologic injury to those who did not. The instrument is the functional status scale score.

The Functional Status Scale (FSS) is a valid and reliable assessment method to quantify functional status. The FSS includes 6 domains: mental status, sensory functioning, communication, motor function, feeding, and respiratory. Scores for each domain range from 1 (normal) to 5 (very severe dysfunction) with total scores ranging from 6 to 30.

Comparative difference in the change in child fatiguebaseline and 1 year after pediatric intensive care unit discharge

This secondary comparative long-term outcome is measured among both usual care ECMO and PROSpect protocolized therapy groups. This outcome compares the change in child fatigue as measured at baseline and 12 months after PICU discharge between matched children in the two groups. The instrument is the age-appropriate PedsQL fatigue scale for acute illness.

The PedsQL™ Multi-dimensional Fatigue Scale - Acute Version is an 18-item scale that encompasses three domains: General Fatigue, Sleep/Rest Fatigue and Cognitive Fatigue. The scale ranges from 0 to 100, with higher scores indicating fewer problems and better health-related quality of life.

Comparative difference in new morbiditybaseline and 1 year after pediatric intensive care unit discharge

This secondary comparative long-term outcome is measured among both usual care ECMO and PROSpect protocolized therapy groups. A new morbidity is defined as a change in the functional status scale instrument score by 3 or more, as previously described. This outcome compares the change in the proportion of matched children who acquire a new morbidity as measured at baseline and 12 months after PICU discharge between the two groups.

The Functional Status Scale is a valid and reliable assessment method to quantify functional status. The FSS includes 6 domains: mental status, sensory functioning, communication, motor function, feeding, and respiratory. Scores for each domain range from 1 (normal) to 5 (very severe dysfunction) with total scores ranging from 6 to 30.

Difference between groups in pneumothorax28 days after day in illness patients are matched or during hospitalization

This secondary comparative short-term outcome is measured among both usual care ECMO and PROSpect protocolized therapy groups. This outcome compares the difference in the proportion of matched children who suffer a pulmonary complication of a new pneumothorax at 28 days between children in the two groups.

Comparative difference in the change in family impact of the child's healthbaseline and 1 year after pediatric intensive care unit discharge

This secondary comparative long-term outcome is measured among both usual care ECMO and PROSpect protocolized therapy groups. This outcome compares the change in family impact of the child's health as measured at baseline and 12 months after PICU discharge between matched children in the two groups. The instrument is the PedsQL family impact module for acute illness.

The PedsQL™ Family Impact Module - Acute Version is a 36-item scale that encompasses eight domains: Physical Functioning, Emotional Functioning, Social Functioning, Cognitive Functioning, Communication, Worry, Daily Activities, and Family Relationships. The scale ranges from 0 to 100, with higher scores indicating fewer problems.

Comparative difference in the change in the psychosocial component of health-related quality of lifebaseline and 1 year after pediatric intensive care unit discharge

This secondary comparative long-term outcome is measured among both usual care ECMO and PROSpect protocolized therapy groups. This outcome compares the change in the psychosocial component of health-related quality of life as measured at baseline and 12 months after PICU discharge between matched children in the two groups. The instrument is the age-appropriate psychosocial health summary score from PedsQL 4.0 generic core scales for acute illness.

PedsQL 4.0 Generic Core Scales and Infant Scales - Acute Version are parent proxy-report scales. The scale ranges from 0 to 100, with higher scores indicating fewer problems. The psychosocial component of the PedsQL 4.0 Generic Core Scales is composed of three of the four domains: emotional functioning, social functioning, and school functioning. The PedsQL Infant Scales psychosocial component is composed of three of the five domains: emotional functioning, social functioning, and cognitive functioning.

Comparative difference in the in change in the physical component of health-related quality of lifebaseline and 1 year after pediatric intensive care unit discharge

This secondary comparative long-term outcome is measured among both usual care ECMO and PROSpect protocolized therapy groups. This outcome compares the change in the physical component of health-related quality of life as measured at baseline and 12 months after PICU discharge between matched children in the two groups. The instrument is the age-appropriate physical health summary score from PedsQL 4.0 generic core scales for acute illness.

PedsQL 4.0 Generic Core Scales and Infant Scales - Acute Version are parent proxy-report scales. The scales range from 0 to 100, with higher scores indicating fewer problems. The physical component of the PedsQL 4.0 Generic Core Scales is composed of one of the four domains: physical functioning. The PedsQL Infant Scales physical component is composed of two of the five domains: physical functioning and physical symptoms.

Comparative change in respiratory supportbaseline and 1 year after pediatric intensive care unit discharge

This secondary comparative long-term outcome is measured among both usual care ECMO and PROSpect protocolized therapy groups. This outcome compares the change in respiratory support as measured at baseline and 12 months after PICU discharge between matched children in the two groups. The instrument is the respiratory subscale of the functional status scale score.

The Functional Status Scale (FSS) is a valid and reliable assessment method to quantify functional status with 6 domains. This measure of breathing support will rely on the FSS respiratory domain. The respiratory domain score ranges from 1 (normal) to 5 (very severe dysfunction).

Trial Locations

Locations (99)

Children's of Alabama

🇺🇸

Birmingham, Alabama, United States

Phoenix Children's Hospital

🇺🇸

Phoenix, Arizona, United States

Arkansas Children's Hospital

🇺🇸

Little Rock, Arkansas, United States

Loma Linda University Children's Hospital

🇺🇸

Loma Linda, California, United States

UCLA Mattel Children's Hospital

🇺🇸

Los Angeles, California, United States

Valley Children's Hospital

🇺🇸

Madera, California, United States

UCSF Benioff Children's Hospital Oakland

🇺🇸

Oakland, California, United States

Children's Hospital of Orange County

🇺🇸

Orange, California, United States

Lucile Packard Children's Hospital Stanford

🇺🇸

Palo Alto, California, United States

UCSF Benioff Children's Hospital - San Francisco

🇺🇸

San Francisco, California, United States

Children's Hospital Colorado

🇺🇸

Aurora, Colorado, United States

Connecticut Children's Medical Center

🇺🇸

Hartford, Connecticut, United States

Yale New Haven Children's Hospital

🇺🇸

New Haven, Connecticut, United States

Nemours Children's Hospital, Delaware

🇺🇸

Wilmington, Delaware, United States

UF Health Shands Children's Hospital

🇺🇸

Gainesville, Florida, United States

Nicklaus Children's Hospital

🇺🇸

Miami, Florida, United States

Orlando Health Arnold Palmer Hospital for Children

🇺🇸

Orlando, Florida, United States

Nemours Children's Hospital, Florida

🇺🇸

Orlando, Florida, United States

Children's Healthcare of Atlanta

🇺🇸

Atlanta, Georgia, United States

Kapi'olani Medical Center for Women & Children

🇺🇸

Honolulu, Hawaii, United States

Ann & Robert H. Lurie Children's Hospital of Chicago

🇺🇸

Chicago, Illinois, United States

Comer Children's Hospital

🇺🇸

Chicago, Illinois, United States

OSF Healthcare Children's Hospital of Illinois

🇺🇸

Peoria, Illinois, United States

Riley Hospital for Children

🇺🇸

Indianapolis, Indiana, United States

University of Iowa Health Care Stead Family Children's Hospital

🇺🇸

Iowa City, Iowa, United States

Norton Children's Hospital

🇺🇸

Louisville, Kentucky, United States

Ochsner LSU Health Shreveport

🇺🇸

Shreveport, Louisiana, United States

University of Maryland Children's Hospital

🇺🇸

Baltimore, Maryland, United States

Johns Hopkins Children's Center

🇺🇸

Baltimore, Maryland, United States

Boston Children's Hospital

🇺🇸

Boston, Massachusetts, United States

Children's Hospital of Michigan

🇺🇸

Detroit, Michigan, United States

Helen DeVos Children's Hospital

🇺🇸

Grand Rapids, Michigan, United States

Children's Minnesota Hospital

🇺🇸

Minneapolis, Minnesota, United States

M Health Fairview Masonic Children's Hospital

🇺🇸

Minneapolis, Minnesota, United States

Mayo Eugenio Litta Children's Hospital

🇺🇸

Rochester, Minnesota, United States

Children's Mercy

🇺🇸

Kansas City, Missouri, United States

Cardinal Glennon Children's Hospital

🇺🇸

St. Louis, Missouri, United States

St. Louis Children's Hospital

🇺🇸

St. Louis, Missouri, United States

Children's Nebraska

🇺🇸

Omaha, Nebraska, United States

UNM Children's Hospital

🇺🇸

Albuquerque, New Mexico, United States

John R. Oishei Children's Hospital

🇺🇸

Buffalo, New York, United States

Hassenfeld Children's Hospital at NYU Langone

🇺🇸

New York, New York, United States

NewYork-Presbyterian Morgan Stanley Children's Hospital

🇺🇸

New York, New York, United States

NewYork-Presbyterian Komansky Children's Hospital

🇺🇸

New York, New York, United States

Cohen Children's Medical Center

🇺🇸

Queens, New York, United States

N.C. Children's Hospital

🇺🇸

Chapel Hill, North Carolina, United States

Duke Children's Hospital & Health Center

🇺🇸

Durham, North Carolina, United States

Atrium Health Wake Forest Baptist | Brenner Children's Hospital

🇺🇸

Winston-Salem, North Carolina, United States

Akron Children's Hospital

🇺🇸

Akron, Ohio, United States

Cincinnati Children's Hospital Medical Center

🇺🇸

Cincinnati, Ohio, United States

Cleveland Clinic Children's Hospital

🇺🇸

Cleveland, Ohio, United States

Nationwide Children's Hospital

🇺🇸

Columbus, Ohio, United States

Oklahoma Children's Hospital OU Health

🇺🇸

Oklahoma City, Oklahoma, United States

OHSU Doernbecher Children's Hospital

🇺🇸

Portland, Oregon, United States

Penn State Health Children's Hospital

🇺🇸

Hershey, Pennsylvania, United States

Children's Hospital of Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

UPMC Children's Hospital of Pittsburgh

🇺🇸

Pittsburgh, Pennsylvania, United States

Hasbro Children's

🇺🇸

Providence, Rhode Island, United States

MUSC Shawn Jenkins Children's Hospital

🇺🇸

Charleston, South Carolina, United States

Sanford Children's Hospital

🇺🇸

Sious Falls, South Dakota, United States

Le Bonheur Children's Hospital

🇺🇸

Memphis, Tennessee, United States

Monroe Carell Jr. Children's Hospital at Vanderbilt

🇺🇸

Nashville, Tennessee, United States

Dell Children's Medical Center

🇺🇸

Austin, Texas, United States

Medical City Children's Hospital

🇺🇸

Dallas, Texas, United States

Children's Medical Center Dallas

🇺🇸

Dallas, Texas, United States

Children's Memorial Hermann Hospital

🇺🇸

Houston, Texas, United States

Texas Children's Hospital

🇺🇸

Houston, Texas, United States

University Health Women's & Children's Hospital

🇺🇸

San Antonio, Texas, United States

Primary Children's Hospital

🇺🇸

Salt Lake City, Utah, United States

UVA Children's Hospital

🇺🇸

Charlottesville, Virginia, United States

Inova L.J. Murphy Children's Hospital

🇺🇸

Falls Church, Virginia, United States

Children's Hospital of Richmond at VCU

🇺🇸

Richmond, Virginia, United States

Seattle Children's Hospital

🇺🇸

Seattle, Washington, United States

UW Health American Family Children's Hospital

🇺🇸

Madison, Wisconsin, United States

Children's Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

The Royal Children's Hospital Melbourne

🇦🇺

Melbourne, Australia

Perth Children's Hospital

🇦🇺

Perth, Australia

Queensland Children's Hospital

🇦🇺

South Brisbane, Australia

The Children's Hospital at Westmead

🇦🇺

Westmead, Australia

Stollery Children's Hospital

🇨🇦

Edmonton, Alberta, Canada

The Hospital for Sick Children

🇨🇦

Toronto, Ontario, Canada

Pontificia Universidad

🇨🇱

Santiago, Chile

Fundacion Cardiovascular De Colombia

🇨🇴

Floridablanca, Colombia

Istituto Giannina Gaslini

🇮🇹

Genoa, Italy

Starship Children's Hospital

🇳🇿

Grafton, Aukland, New Zealand

Hospital de Santa Maria

🇵🇹

Lisbon, Portugal

Children's Hospital and Vall d' Hebron Women's Hospital

🇪🇸

Barcelona, Spain

Sant Joan de Deu Barcelona Hospital

🇪🇸

Barcelona, Spain

Hospital Gregorio Maranon

🇪🇸

Madrid, Spain

ECMO Centrum Karolinska

🇸🇪

Stockholm, Sweden

Royal Hospital for Children

🇬🇧

Glasgow, United Kingdom

Leicester Children's Hospital

🇬🇧

Leicester, United Kingdom

Alder Hey Children's Hospital

🇬🇧

Liverpool, United Kingdom

Evelina London Children's Hospital

🇬🇧

London, United Kingdom

Royal Brompton Hospital

🇬🇧

London, United Kingdom

Great Ormond Street Hospital for Children

🇬🇧

London, United Kingdom

Freeman Hospital

🇬🇧

Newcastle Upon Tyne, United Kingdom

Southampton Children's Hospital

🇬🇧

Southampton, United Kingdom

University of Michigan - Mott Children's Hospital

🇺🇸

Ann Arbor, Michigan, United States

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