Clinical trial NCT06690801: Dead Space and Inhaled Nitric Oxide in Pediatric Acute Respiratory Distress Syndrome
Official title: Dead Space and Inhaled Nitric Oxide in Pediatric Acute Respiratory Distress Syndrome
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Acute Respiratory Distress Syndrome
Keywords: Pediatrics
Mechanical Ventilation
Inhaled Nitric Oxide
Lead sponsor: Children's Hospital Los Angeles
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2024-11-15
Enrollment: 1260
Sex: ALL
Minimum age (years): 0
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Children with moderate to severe ARDS

Brief summary: The goal of this observational study is to determine whether a marker of dead space (the end-tidal to alveolar dead space fraction \[AVDSf\]) is more strongly associated with mortality risk than markers of oxygenation abnormality (oxygenation index) and to determine whether dead space (AVDSf) is an important marker of heterogeneity in the inhaled nitric oxide (iNO) treatment effect for children with acute respiratory distress syndrome (ARDS).

The study aims are:

1. To validate AVDSf for risk stratification of mortality in pediatric ARDS
2. To determine if there is heterogeneity in treatment effect for iNO defined by AVDSf
3. To detect the association between AVDSf and microvascular dysfunction trajectory and whether iNO therapy modifies this association

This is a prospective, multicenter observational study of 1260 mechanically ventilated children with moderate to severe ARDS. In a subgroup of 450 children with severe ARDS, longitudinal blood samples will be obtained to measure plasma protein markers.


Eligibility criteria: Inclusion Criteria:

* Age \>37 weeks corrected gestational age to 21 years, including adults lacking the capacity to consent.
* Within 72 hours of the start of invasive mechanical ventilation and meet the criteria for pediatric ARDS (new infiltrate on chest imaging and a known ARDS risk factor within 7 days of the onset of hypoxemia) and either meet criteria for moderate or severe pediatric ARDS between 4-72 hours of IMV (OI ≥ 8 or OSI ≥ 7.5) OR have an OI ≥ 20 or an OSI ≥ 14 x 15 minutes between 0-4 hours of IMV.
* Subgroup of children eligible for longituduinal Blood Collection: Children with severe PARDS (OI ≥ 16 or an OSI ≥ 12 between 4-72 hours of IMV) or those with an OI ≥ 20 or an OSI ≥ 14 for 15 minutes between 0-4 hours of IMV will be eligible for collection of longitudinal plasma samples.

Exclusion Criteria:

* Non-conventional invasive mechanical ventilation (i.e. High Frequency Oscillatory Ventilation, Airway Pressure Release Ventilation) at the time of ICU admission
* ECMO or iNO (or other inhaled pulmonary vasodilator therapy) at the time of ICU admission
* Significant lower airways obstruction (examination of ventilator and capnography waveforms by site study or medical team)
* Air leak \>20% (endotracheal tube, tracheostomy tube, or thoracostomy tube)
* Home Invasive Mechanical Ventilation
* Cyanotic Congenital Heart Disease
* Previous enrollment in the DiNO study
* Do not resuscitate order at the time of pediatric ARDS diagnosis.
* Blood gas not obtained prior to initiation of ECMO, iNO, or non-conventional ventilation.

Primary outcomes:
measure: Number of participants that experience all-cause mortality within 28 days from start of invasive mechanical ventilation
timeFrame: From the start of invasive mechanical ventilation to 28 days
Secondary outcomes:
measure: Number of participants that experience all-cause mortality within 90 days from start of invasive mechanical ventilation
timeFrame: From the start of invasive mechanical ventilation to 90 days
measure: 28-Day Ventilator-Free Days
timeFrame: From the start of invasive mechanical ventilation to 28 days
measure: The days on invasive mechanical ventilation for survivors of ARDS
timeFrame: From the start of invasive mechanical ventilation to the end of invasive mechanical ventilation (or 90 days after the start of invasive mechanical ventilation if the patient is still on invasive mechanical ventilation at 90 days)
measure: The number of non-pulmonary organ failure free days within the first 14 days of invasive mechanical ventilation
timeFrame: From the start of invasive mechanical ventilation to 14 days
measure: The number of non-pulmonary organ failures 21 days after the start of invasive mechanical ventilation
timeFrame: 21 days after the start of invasive mechanical ventilation
measure: The number of non-pulmonary organ failures 28 days after the start of invasive mechanical ventilation
timeFrame: 28 days after the start of invasive mechanical ventilation
measure: The number of non-pulmonary organs that newly meet failure criteria or have an increase in the severity of organ failure within the first 14 days of invasive mechanical ventilation
timeFrame: From the start of invasive mechanical ventilation to 14 days
measure: The development of renal failure within the first 14 days of invasive mechanical ventilation
timeFrame: From the start of invasive mechanical ventilation to 14 days
measure: Non-pulmonary organ failure phenotypes that develop within the first 14 days of invasive mechanical ventilation
timeFrame: From the start of invasive mechanical ventilation to 14 days
measure: Cumulative non-pulmonary organ failure severity in the first 14 days of invasive mechanical ventilation
timeFrame: From the start of invasive mechanical ventilation to 14 days
measure: The change in functional status score from baseline to hospital discharge
timeFrame: From baseline to hospital discharge (or 90 days after the start of invasive mechanical ventilation)
measure: The change in pediatric overall performance score from baseline to hospital discharge
timeFrame: From baseline to hospital discharge (or 90 days after the start of invasive mechanical ventilation)
measure: The change in pediatric cerebral performance score from baseline to hospital discharge
timeFrame: From baseline to hospital discharge (or 90 days after the start of invasive mechanical ventilation)
measure: All-cause mortality or the use of extracorporeal membrane oxygenation (ECMO) therapy within 28 days after the start of invasive mechanical ventilation
timeFrame: From the start of invasive mechanical ventilation to 28 days
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Denver
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan / CS Mott Children's Hospital
state: Michigan
city: Omaha
country: United States
facility: University of Nebraska Medical Center / Children's Hospital and Medical Center
state: Nebraska
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Houston
country: United States
facility: Texas Children's Hospital Baylor College of Medicine
state: Texas
city: Madison
country: United States
facility: American Family Children's Hospital / University of Wisconsin-Madison
state: Wisconsin
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin / Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Children's Hospital Los Angeles
name: Anoopindar M Bhalla, MD
role: PRINCIPAL_INVESTIGATOR
References: