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

University of Michigan

Status: Enrolling

Conditions: Acute Respiratory Distress Syndrome; Extracorporeal Membrane Oxygenation

Treatments: Device: ECMO support; Other: PROSpect protocolized therapies

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT05388708

R01HL153519-01 (U.S. NIH Grant/Contract)

HUM00173031

Details and patient eligibility

About

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.

Full 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.

Enrollment: 550 estimated patients

Sex: All

Ages: 14 days to 20 years old

Volunteers: No Healthy Volunteers

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

Trial design

550 participants in 2 patient groups

Usual care ECMO Cohort

Description:

The 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.

Treatment:

Device: ECMO support

PROSpect protocolized therapies cohort

Description:

The 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.

Treatment:

Other: PROSpect protocolized therapies