Clinical trial NCT05388708: ARDS in Children and ECMO Initiation Strategies Impact on Neurodevelopment (ASCEND)
Official title: ARDS in Children and ECMO Initiation Strategies Impact on Neurodevelopment (ASCEND)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Acute Respiratory Distress Syndrome
Extracorporeal Membrane Oxygenation
Keywords: ARDS
Acute Respiratory Distress Syndrome
Extracorporeal Membrane Oxygenation
ECMO
Extracorporeal Life Support
ECLS
Pediatric
Quality of Life
Functional Status
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2022-05-24
Enrollment: 550
Sex: ALL
Minimum age (years): 14
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population comes from pediatric patients hospitalized for respiratory distress requiring intubation and ECMO. Namely, children are eligible if they have moderate to severe PARDS, meet inclusion criteria and do not have the exclusion criteria listed below under exclusion criteria. Children in ELSO's usual care ECMO cohort also cannot be enrolled in PROSpect, and they must have respiratory ECMO initiated at an ELSO site within 10 days of intubation.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in functional status
timeFrame: baseline and 1 year after pediatric intensive care unit discharge
measure: Change in health-related quality of life
timeFrame: baseline and 1 year after pediatric intensive care unit discharge
measure: The proportion of children with a new morbidity
timeFrame: baseline and 1 year after pediatric intensive care unit discharge
measure: All-cause mortality at hospital discharge or 90-days
timeFrame: 90 days after the day of illness on which patients from the two cohorts are matched
measure: Comparative change in one-year functional status
timeFrame: baseline and 1 year after pediatric intensive care unit discharge
measure: Comparative change in one-year health-related quality of life
timeFrame: baseline and 1 year after pediatric intensive care unit discharge
Secondary outcomes:
measure: Change in pediatric overall performance category
timeFrame: baseline and 1 year after pediatric intensive care unit discharge
measure: Change in pediatric cerebral performance category
timeFrame: baseline and 1 year after pediatric intensive care unit discharge
measure: Change in breathing support
timeFrame: baseline and 1 year after pediatric intensive care unit discharge
measure: Change in the psychosocial component of health-related quality of life
timeFrame: baseline and 1 year after pediatric intensive care unit discharge
measure: Change in the physical component of health-related quality of life
timeFrame: baseline and 1 year after pediatric intensive care unit discharge
measure: Change in child fatigue
timeFrame: baseline and 1 year after pediatric intensive care unit discharge
measure: Change in family impact of the child's health
timeFrame: baseline and 1 year after pediatric intensive care unit discharge
measure: Change in one-year functional status of children suffering a neurologic injury
timeFrame: baseline and 1 year after pediatric intensive care unit discharge
measure: Difference between groups in intracranial bleeding or ischemic stroke
timeFrame: 28 days after day in illness patients are matched or during hospitalization
measure: Difference between groups in pneumothorax
timeFrame: 28 days after day in illness patients are matched or during hospitalization
measure: Comparative difference in the change in child fatigue
timeFrame: baseline and 1 year after pediatric intensive care unit discharge
measure: Comparative difference in the change in family impact of the child's health
timeFrame: baseline and 1 year after pediatric intensive care unit discharge
measure: Comparative difference in the change in the psychosocial component of health-related quality of life
timeFrame: baseline and 1 year after pediatric intensive care unit discharge
measure: Comparative difference in the in change in the physical component of health-related quality of life
timeFrame: baseline and 1 year after pediatric intensive care unit discharge
measure: Comparative change in respiratory support
timeFrame: baseline and 1 year after pediatric intensive care unit discharge
measure: Comparative difference in new morbidity
timeFrame: baseline and 1 year after pediatric intensive care unit discharge
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Loma Linda
country: United States
facility: Loma Linda University Children's Hospital
state: California
city: Los Angeles
country: United States
facility: UCLA Mattel Children's Hospital
state: California
city: Madera
country: United States
facility: Valley Children's Hospital
state: California
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital Oakland
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital Stanford
state: California
city: San Francisco
country: United States
facility: UCSF Benioff Children's Hospital - San Francisco
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: New Haven
country: United States
facility: Yale New Haven Children's Hospital
state: Connecticut
city: Wilmington
country: United States
facility: Nemours Children's Hospital, Delaware
state: Delaware
city: Gainesville
country: United States
facility: UF Health Shands Children's Hospital
state: Florida
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Orlando
country: United States
facility: Orlando Health Arnold Palmer Hospital for Children
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Hospital, Florida
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Honolulu
country: United States
facility: Kapi'olani Medical Center for Women & Children
state: Hawaii
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Chicago
country: United States
facility: Comer Children's Hospital
state: Illinois
city: Peoria
country: United States
facility: OSF Healthcare Children's Hospital of Illinois
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Health Care Stead Family Children's Hospital
state: Iowa
city: Louisville
country: United States
facility: Norton Children's Hospital
state: Kentucky
city: Shreveport
country: United States
facility: Ochsner LSU Health Shreveport
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Children's Hospital
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Children's Center
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan - Mott Children's Hospital
state: Michigan
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Children's Minnesota Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: M Health Fairview Masonic Children's Hospital
state: Minnesota
city: Rochester
country: United States
facility: Mayo Eugenio Litta Children's Hospital
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy
state: Missouri
city: St. Louis
country: United States
facility: Cardinal Glennon Children's Hospital
state: Missouri
city: St. Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
city: Omaha
country: United States
facility: Children's Nebraska
state: Nebraska
city: Albuquerque
country: United States
facility: UNM Children's Hospital
state: New Mexico
city: Buffalo
country: United States
facility: John R. Oishei Children's Hospital
state: New York
city: New York
country: United States
facility: Hassenfeld Children's Hospital at NYU Langone
state: New York
city: New York
country: United States
facility: NewYork-Presbyterian Morgan Stanley Children's Hospital
state: New York
city: New York
country: United States
facility: NewYork-Presbyterian Komansky Children's Hospital
state: New York
city: Queens
country: United States
facility: Cohen Children's Medical Center
state: New York
city: Chapel Hill
country: United States
facility: N.C. Children's Hospital
state: North Carolina
city: Durham
country: United States
facility: Duke Children's Hospital & Health Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Atrium Health Wake Forest Baptist | Brenner Children's Hospital
state: North Carolina
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Children's Hospital OU Health
state: Oklahoma
city: Portland
country: United States
facility: OHSU Doernbecher Children's Hospital
state: Oregon
city: Hershey
country: United States
facility: Penn State Health Children's Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
city: Providence
country: United States
facility: Hasbro Children's
state: Rhode Island
city: Charleston
country: United States
facility: MUSC Shawn Jenkins Children's Hospital
state: South Carolina
city: Sious Falls
country: United States
facility: Sanford Children's Hospital
state: South Dakota
city: Memphis
country: United States
facility: Le Bonheur Children's Hospital
state: Tennessee
city: Nashville
country: United States
facility: Monroe Carell Jr. Children's Hospital at Vanderbilt
state: Tennessee
city: Austin
country: United States
facility: Dell Children's Medical Center
state: Texas
city: Dallas
country: United States
facility: Medical City Children's Hospital
state: Texas
city: Dallas
country: United States
facility: Children's Medical Center Dallas
state: Texas
city: Houston
country: United States
facility: Children's Memorial Hermann Hospital
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: San Antonio
country: United States
facility: University Health Women's & Children's Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Charlottesville
country: United States
facility: UVA Children's Hospital
state: Virginia
city: Falls Church
country: United States
facility: Inova L.J. Murphy Children's Hospital
state: Virginia
city: Richmond
country: United States
facility: Children's Hospital of Richmond at VCU
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Madison
country: United States
facility: UW Health American Family Children's Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: Children's Wisconsin
state: Wisconsin
city: Melbourne
country: Australia
facility: The Royal Children's Hospital Melbourne
city: Perth
country: Australia
facility: Perth Children's Hospital
city: South Brisbane
country: Australia
facility: Queensland Children's Hospital
city: Westmead
country: Australia
facility: The Children's Hospital at Westmead
city: Edmonton
country: Canada
facility: Stollery Children's Hospital
state: Alberta
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Santiago
country: Chile
facility: Pontificia Universidad
city: Floridablanca
country: Colombia
facility: Fundacion Cardiovascular De Colombia
city: Genoa
country: Italy
facility: Istituto Giannina Gaslini
city: Grafton
country: New Zealand
facility: Starship Children's Hospital
state: Aukland
city: Lisbon
country: Portugal
facility: Hospital de Santa Maria
city: Barcelona
country: Spain
facility: Children's Hospital and Vall d' Hebron Women's Hospital
city: Barcelona
country: Spain
facility: Sant Joan de Deu Barcelona Hospital
city: Madrid
country: Spain
facility: Hospital Gregorio Maranon
city: Stockholm
country: Sweden
facility: ECMO Centrum Karolinska
city: Glasgow
country: United Kingdom
facility: Royal Hospital for Children
city: Leicester
country: United Kingdom
facility: Leicester Children's Hospital
city: Liverpool
country: United Kingdom
facility: Alder Hey Children's Hospital
city: London
country: United Kingdom
facility: Evelina London Children's Hospital
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
city: Newcastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital
city: Southampton
country: United Kingdom
facility: Southampton Children's Hospital
Study officials:
affiliation: University of Michigan
name: Ryan Barbaro, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fiser DH. Assessing the outcome of pediatric intensive care. J Pediatr. 1992 Jul;121(1):68-74. doi: 10.1016/s0022-3476(05)82544-2.
citation: Pollack MM, Holubkov R, Glass P, Dean JM, Meert KL, Zimmerman J, Anand KJ, Carcillo J, Newth CJ, Harrison R, Willson DF, Nicholson C; Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Functional Status Scale: new pediatric outcome measure. Pediatrics. 2009 Jul;124(1):e18-28. doi: 10.1542/peds.2008-1987.
citation: Varni JW, Seid M, Kurtin PS. PedsQL 4.0: reliability and validity of the Pediatric Quality of Life Inventory version 4.0 generic core scales in healthy and patient populations. Med Care. 2001 Aug;39(8):800-12. doi: 10.1097/00005650-200108000-00006.
citation: Varni JW, Seid M, Rode CA. The PedsQL: measurement model for the pediatric quality of life inventory. Med Care. 1999 Feb;37(2):126-39. doi: 10.1097/00005650-199902000-00003.
citation: Pollack MM, Holubkov R, Funai T, Berger JT, Clark AE, Meert K, Berg RA, Carcillo J, Wessel DL, Moler F, Dalton H, Newth CJ, Shanley T, Harrison RE, Doctor A, Jenkins TL, Tamburro R, Dean JM; Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Simultaneous Prediction of New Morbidity, Mortality, and Survival Without New Morbidity From Pediatric Intensive Care: A New Paradigm for Outcomes Assessment. Crit Care Med. 2015 Aug;43(8):1699-709. doi: 10.1097/CCM.0000000000001081.
citation: Keim G, Watson RS, Thomas NJ, Yehya N. New Morbidity and Discharge Disposition of Pediatric Acute Respiratory Distress Syndrome Survivors. Crit Care Med. 2018 Nov;46(11):1731-1738. doi: 10.1097/CCM.0000000000003341.
citation: Combes A, Hajage D, Capellier G, Demoule A, Lavoue S, Guervilly C, Da Silva D, Zafrani L, Tirot P, Veber B, Maury E, Levy B, Cohen Y, Richard C, Kalfon P, Bouadma L, Mehdaoui H, Beduneau G, Lebreton G, Brochard L, Ferguson ND, Fan E, Slutsky AS, Brodie D, Mercat A; EOLIA Trial Group, REVA, and ECMONet. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome. N Engl J Med. 2018 May 24;378(21):1965-1975. doi: 10.1056/NEJMoa1800385.