Acute Respiratory Distress SyndromeDiNONCT06690801
Dead Space and Inhaled Nitric Oxide in Pediatric Acute Respiratory Distress Syndrome
An observational study of Acute Respiratory Distress Syndrome, run by Children's Hospital Los Angeles at 10 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 0 to 21 years
- Conditions the study is for
- Acute Respiratory Distress Syndrome
- How many people
- 1,260 participants
- Where
- 10 sitesUnited States
- Study dates
- 3 Oct 2024to 1 Feb 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Children with moderate to severe ARDS
Who may be able to join
- 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.
Who cannot join
- 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
Show all 9Show fewer
- 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.
Trial locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
10 sites in 1 country
United States10 sites, 9 recruiting
- Active, not recruiting
University of Michigan / CS Mott Children's Hospital
Ann Arbor, Michigan, 48109
- Not yet recruiting
Boston Children's Hospital
Boston, Massachusetts, 02115
Sally Vitali, sally.vitali@childrens.harvard.edu
Sally Vitali, MD
- Not yet recruiting
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Steve Standage, steve.standage@cchmc.org
Steve Standage, MD
- Not yet recruiting
Children's Hospital Colorado
Denver, Colorado, 80204
Aline Maddux, aline.maddux@childrenscolorado.org
Aline Maddux, MD
- Not yet recruiting
Texas Children's Hospital Baylor College of Medicine
Houston, Texas, 77030
Manpreet Virk, manpreet.virk@bcm.edu
Manpreet Virk, MD
- Recruiting
Children's Hospital Los Angeles
Los Angeles, California, 90027
Jeni Kwok, JD, 323-660-2450 ext. 16330, ymkwok@chla.usc.edu
Anoopindar Bhalla, MD
- Not yet recruiting
American Family Children's Hospital / University of Wisconsin-Madison
Madison, Wisconsin, 53792
Awni Al-Subu, al-subu@pediatrics.wisc.edu
Awni Al-Subu, MD
- Not yet recruiting
Children's Hospital of Wisconsin / Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Jasmine Dowell, jdowell@mcw.edu
Jasmine Dowell, MD
- Not yet recruiting
University of Nebraska Medical Center / Children's Hospital and Medical Center
Omaha, Nebraska, 68198
Eleanor Gradidge, egradidge@childrensnebraska.org
Eleanor Gradidge, MD
- Not yet recruiting
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Adam Himebauch, himebaucha@chop.edu
Adam Himebauch, MD
About this study
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:
Read more
- To validate AVDSf for risk stratification of mortality in pediatric ARDS
- To determine if there is heterogeneity in treatment effect for iNO defined by AVDSf
- 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.
- Conditions
- Acute Respiratory Distress Syndrome
- Keywords
- Pediatrics, Mechanical Ventilation, Inhaled Nitric Oxide
- Medical subject headings
- Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Children with moderate to severe ARDS | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants that experience all-cause mortality within 28 days from start of invasive mechanical ventilation
28 day all-cause mortality
Measured: From the start of invasive mechanical ventilation to 28 days
Secondary outcomes (14)
Number of participants that experience all-cause mortality within 90 days from start of invasive mechanical ventilation
90 day all-cause mortality
Measured: From the start of invasive mechanical ventilation to 90 days
28-Day Ventilator-Free 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.
Measured: From the start of invasive mechanical ventilation to 28 days
The days on invasive mechanical ventilation for survivors of ARDS
The number of days that a patient that survives is on invasive mechanical ventilation (up to 90 days)
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: From the start of invasive mechanical ventilation to 14 days
The development of renal failure within the first 14 days of invasive mechanical ventilation
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.
Measured: 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
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.
Measured: 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
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.
Measured: From the start of invasive mechanical ventilation to 14 days
The change in functional status score from baseline to hospital discharge
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.
Measured: 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
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.
Measured: From baseline to hospital discharge (or 90 days after the start of invasive mechanical ventilation)
The change in pediatric cerebral performance score from baseline to hospital discharge
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.
Measured: From baseline to hospital discharge (or 90 days after the start of invasive mechanical ventilation)
All-cause mortality or the use of extracorporeal membrane oxygenation (ECMO) therapy within 28 days after the start of invasive mechanical ventilation
Patients who experience mortality or use of ECMO within 28 days of the start of invasive mechanical ventilation
Measured: From the start of invasive mechanical ventilation to 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2024
- Study start3 Oct 2024
- Primary completion1 Dec 2028 (estimated)
- Study completion1 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- More trials run by Children's Hospital Los AngelesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,260 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Anoopindar Bhalla, Children's Hospital Los Angeles
- Investigators
- Anoopindar M Bhalla, MD, Principal investigator, Children's Hospital Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06690801
- Sponsor's protocol ID
- CHLA-24-00209
- Other IDs
- R01HL173488
- Acronym
- DiNO
- Status last verified
- Nov 2024
- First submitted
- 8 Nov 2024
- Last updated
- 15 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified public use dataset will be created.
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dead Space and Inhaled Nitric Oxide in Pediatric Acute Respiratory Distress Syndrome
- ClinicalTrials.gov ID
- NCT06690801
- Acronym / sponsor ID
- DiNO / CHLA-24-00209
- Conditions
- Acute Respiratory Distress Syndrome
- Keywords
- Pediatrics, Mechanical Ventilation, Inhaled Nitric Oxide
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 1,260 participants (estimated)
- Lead sponsor
- Children's Hospital Los AngelesUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 3 Oct 2024 (actual)
- Primary completion
- 1 Dec 2028 (estimated)
- Study completion
- 1 Feb 2029 (estimated)
- First posted
- 15 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To validate AVDSf for risk stratification of mortality in pediatric ARDS
- To determine if there is heterogeneity in treatment effect for iNO defined by AVDSf
- 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Children with moderate to severe ARDS | – | – |
Who may qualify
- Ages
- 0 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Children with moderate to severe ARDS
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
14 secondary outcomes
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
28-Day Ventilator-Free Days
Time frame: From the start of invasive mechanical ventilation to 28 days
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 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
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
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
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
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
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
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
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 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 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)
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2024.
- Individual participant dataSharing planned: Yes. Deidentified public use dataset will be created.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Anoopindar M Bhalla, MD principal investigator
Children's Hospital Los Angeles
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Respiratory Distress Syndrome, run by Children's Hospital Los Angeles at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jeni Kwok (3233617939, dinostudy@chla.usc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2024.