Dead Space and Inhaled Nitric Oxide in Pediatric Acute Respiratory Distress Syndrome

Обзор

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.

Первичные конечные точки

• Number of participants that experience all-cause mortality within 28 days from start of invasive mechanical ventilation [Срок оценки: From the start of invasive mechanical ventilation to 28 days]

Вторичные конечные точки (12)

• Number of participants that experience all-cause mortality within 90 days from start of invasive mechanical ventilation [Срок оценки: From the start of invasive mechanical ventilation to 90 days]
• 28-Day Ventilator-Free Days [Срок оценки: From the start of invasive mechanical ventilation to 28 days]
• The days on invasive mechanical ventilation for survivors of ARDS [Срок оценки: 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)]
• The number of non-pulmonary organ failure free days within the first 14 days of invasive mechanical ventilation [Срок оценки: From the start of invasive mechanical ventilation to 14 days]
• The number of non-pulmonary organ failures 21 days after the start of invasive mechanical ventilation [Срок оценки: 21 days after the start of invasive mechanical ventilation]
• The number of non-pulmonary organ failures 28 days after the start of invasive mechanical ventilation [Срок оценки: 28 days after the start of invasive mechanical ventilation]
• 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 [Срок оценки: From the start of invasive mechanical ventilation to 14 days]
• The development of renal failure within the first 14 days of invasive mechanical ventilation [Срок оценки: From the start of invasive mechanical ventilation to 14 days]
• Non-pulmonary organ failure phenotypes that develop within the first 14 days of invasive mechanical ventilation [Срок оценки: From the start of invasive mechanical ventilation to 14 days]
• Cumulative non-pulmonary organ failure severity in the first 14 days of invasive mechanical ventilation [Срок оценки: From the start of invasive mechanical ventilation to 14 days]
• The change in functional status score from baseline to hospital discharge [Срок оценки: From baseline to hospital discharge (or 90 days after the start of invasive mechanical ventilation)]
• The change in pediatric overall performance score from baseline to hospital discharge [Срок оценки: From baseline to hospital discharge (or 90 days after the start of invasive mechanical ventilation)]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

США · 10 центров

• Children's Hospital Los Angeles — Los Angeles
• Children's Hospital Colorado — Denver
• Boston Children's Hospital — Boston
• University of Michigan / CS Mott Children's Hospital — Ann Arbor
• University of Nebraska Medical Center / Children's Hospital and Medical Center — Omaha
• Cincinnati Children's Hospital Medical Center — Cincinnati
• Children's Hospital of Philadelphia — Philadelphia
• Texas Children's Hospital Baylor College of Medicine — Houston
• … и ещё 2 центра

Идентификаторы

NCT: NCT06690801 · CHLA-24-00209 · R01HL173488

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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