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NCT Number: NCT06690801

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

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.

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Key information

Conditions

Acute Respiratory Distress Syndrome Lung Diseases Respiration Disorders Respiratory Distress Syndrome Respiratory Tract Diseases

Age range

0 year–21 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Children's Hospital Los Angeles, Los Angeles, California, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Primary outcomes

  1. Number of participants that experience all-cause mortality within 28 days from start of invasive mechanical ventilation

    Time frame: From the start of invasive mechanical ventilation to 28 days

    28 day all-cause mortality

Secondary outcomes

  1. Number of participants that experience all-cause mortality within 90 days from start of invasive mechanical ventilation

    Time frame: From the start of invasive mechanical ventilation to 90 days

    90 day all-cause mortality

  2. 28-Day Ventilator-Free Days

    Time frame: From the start of invasive mechanical ventilation to 28 days

    The number of days within the first 28 days of invasive mechanical ventilation for ARDS that a patient is alive and free of mechanical ventilation.

  3. The days on invasive mechanical ventilation for survivors of ARDS

    Time frame: 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 days that a patient that survives is on invasive mechanical ventilation (up to 90 days)

  4. The number of non-pulmonary organ failure free days within the first 14 days of invasive mechanical ventilation

    Time frame: From the start of invasive mechanical ventilation to 14 days

    Organ failure criteria will be determined with the Pediatric Organ Dysfunction Information Update Mandate. We will identify the number of days in the first 14 days of ARDS that a patient is alive and without any non-pulmonary organ failures.

  5. The number of non-pulmonary organ failures 21 days after the start of invasive mechanical ventilation

    Time frame: 21 days after the start of invasive mechanical ventilation

    Organ failure criteria will be determined with the Pediatric Organ Dysfunction Information Update Mandate. The number of non-pulmonary organ failures on day 21 after the start of invasive mechanical ventilation will be identified. Patients that experience mortality prior to 21 days will be considered to have failure of all non-pulmonary organs.

  6. The number of non-pulmonary organ failures 28 days after the start of invasive mechanical ventilation

    Time frame: 28 days after the start of invasive mechanical ventilation

    Organ failure criteria will be determined with the Pediatric Organ Dysfunction Information Update Mandate. The number of non-pulmonary organ failures on day 28 after the start of invasive mechanical ventilation will be identified. Patients that experience mortality prior to 28 days will be considered to have failure of all non-pulmonary organs.

  7. 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

    Time frame: From the start of invasive mechanical ventilation to 14 days

    Organ failure criteria will be determined with the Pediatric Organ Dysfunction Information Update Mandate. We will identify the number of organs during the first 14 days of invasive mechanical ventilation that either have worsening of the severity of failure or new failure after the first day of invasive mechanical ventilation.

  8. The development of renal failure within the first 14 days of invasive mechanical ventilation

    Time frame: From the start of invasive mechanical ventilation to 14 days

    Renal organ failure criteria will be determined with the Pediatric Organ Dysfunction Information Update Mandate. We will identify whether during the first 14 days of invasive mechanical ventilation there is new renal failure after the first day of invasive mechanical ventilation.

  9. Non-pulmonary organ failure phenotypes that develop within the first 14 days of invasive mechanical ventilation

    Time frame: From the start of invasive mechanical ventilation to 14 days

    Organ failure criteria will be determined with the Pediatric Organ Dysfunction Information Update Mandate. We will identify 14-day non-pulmonary organ failure free phenotypes using clustering analyses.

  10. Cumulative non-pulmonary organ failure severity in the first 14 days of invasive mechanical ventilation

    Time frame: From the start of invasive mechanical ventilation to 14 days

    Organ failure scores will be quantified daily with the Pediatric Logistic Organ Dysfunction (PELOD-2) score. Children that die will be assigned the maximum value. The score will be summed over the first 14 days of invasive mechanical ventilation.

  11. The change in functional status score from baseline to hospital discharge

    Time frame: From baseline to hospital discharge (or 90 days after the start of invasive mechanical ventilation)

    The baseline functional status score and the intensive care unit discharge functional status score will be compared and new morbidities will be identified. If the patient is still in the hospital after 90 days of the start of invasive mechanical ventilation the functional status score at 90 days will be used rather than the functional status score at hospital discharge.

  12. The change in pediatric overall performance score from baseline to hospital discharge

    Time frame: From baseline to hospital discharge (or 90 days after the start of invasive mechanical ventilation)

    The baseline pediatric overall performance score and the hospital discharge pediatric overall performance score will be compared and new morbidities will be identified. If the patient is still in the hospital after 90 days of the start of invasive mechanical ventilation the pediatric overall performance score at 90 days will be used rather than the pediatric overall performance score at hospital discharge.

  13. The change in pediatric cerebral performance score from baseline to hospital discharge

    Time frame: From baseline to hospital discharge (or 90 days after the start of invasive mechanical ventilation)

    The baseline pediatric cerebral performance score and the hospital discharge pediatric cerebral performance score will be compared and new morbidities will be identified. If the patient is still in the hospital after 90 days of the start of invasive mechanical ventilation the pediatric cerebral performance score at 90 days will be used rather than the pediatric cerebral performance score at hospital discharge.

  14. All-cause mortality or the use of extracorporeal membrane oxygenation (ECMO) therapy within 28 days after the start of invasive mechanical ventilation

    Time frame: From the start of invasive mechanical ventilation to 28 days

    Patients who experience mortality or use of ECMO within 28 days of the start of invasive mechanical ventilation

Study contacts

Contact information is provided by the study sponsor or research team.

Anoopindar Bhalla, MD

CONTACT

[email protected]

3233617939

Jeni Kwok

CONTACT

[email protected]

3233617939

Sponsors and collaborators

Lead sponsor

Children's Hospital Los Angeles

Other

Collaborators

  • National Heart, Lung, and Blood Institute (NHLBI)

Registry information

Acronym: DiNO

Important dates

Study start
2024
Primary completion
2028
Study completion
2029
First posted
Nov 15, 2024
Registry last updated
Nov 15, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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