Congenital Diaphragmatic HerniaPhase 4NCT05213676
De-implementing Inhaled Nitric Oxide for Congenital Diaphragmatic Hernia
A Phase 4 study testing Inhaled Nitric Oxide (iNO) use and De-implementation of Inhaled Nitric Oxide (iNO) use in people with Congenital Diaphragmatic Hernia, run by The University of Texas Health Science Center, Houston at 19 sites in United States.
Trial summary
The purpose of this study is to determine if de-implementation of inhaled nitric oxide (iNO) in the post-natal resuscitation/stabilization phase affects the composite outcome of extracorporeal life support (ECLS) use and/or mortality, as well as ECLS use, mortality, and/or oxygenation in congenital diaphragmatic… Read more about this study
- Who is it for?
- Ages 0 months to 1 month
- Conditions the study is for
- Congenital Diaphragmatic Hernia
- What is being tested?
- Inhaled Nitric Oxide (iNO) use and De-implementation of Inhaled Nitric Oxide (iNO) use
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 900 participants
- Where
- 19 sitesUnited States
- Study dates
- 1 Nov 2025to 30 Apr 2031
- Phase
- Phase 4
- 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 months to 1 month
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Postnatal, live born neonates with CDH
- Presence of associated or additional anomalies is acceptable for inclusion
- Bochdalek hernia location (right or left)
- Diagnosed prior to 1 month of life
- Born within or transferred to (within 1 week of life) a CDHSG member center participating in the trial
Who cannot join
- CDH diagnosis after 1 month of age
- Morgagni diaphragmatic hernia (central / anterior-medial diaphragmatic defect location)
- Transferred to a CDH Study Group (CDHSG) member center after 1 week of life
- Patients without potential access to iNO
Trial locations and contacts
19 sites in 1 country. Contact the study team or a site near you to ask about taking part.
19 sites in 1 country
United States19 sites, 19 recruiting
- Recruiting
University of Michigan & CS Mott Children's Hospital (UM-CSMott)
Ann Arbor, Michigan, 48109
Erin Perrone, MD, eperrone@med.umich.edu
- Recruiting
Emory University & Children's Healthcare of Atlanta (CHOA)
Atlanta, Georgia, 30322
Sarah Keene, MD, skeene@emory.edu
- Recruiting
University of Colorado & Children's Hospital of Colorado (CU-CHC)
Aurora, Colorado, 80045
Michael W Cookson, MD, Michael.Cookson@childrenscolorado.org
- Recruiting
University of Alabama & Children's Hospital of Alabama (UAB-CoA)
Birmingham, Alabama, 35233
Scott Anderson, MD, Scott.Anderson@childrensal.org
- Recruiting
Harvard University & Boston Children's Hospital (Harvard-BCH)
Boston, Massachusetts, 02115
Jill Zalieckas, MD, MPH, Jill.Zalieckas@childrens.harvard.edu
- Recruiting
Medical University of South Carolina Children's Health (MUSC)
Charleston, South Carolina, 29425
Laura E Hollinger, MD, hollingl@musc.edu
- Recruiting
The University of Texas Health Science Center at Houston
Houston, Texas, 77030
Matthew Harting, MD, MS, FACS, (713) 500-7398, Matthew.T.Harting@uth.tmc.edu
Ashley Ebanks, (832) 325-7234, Ashley.Harmon@uth.tmc.edu
- Recruiting
Indiana University & Riley Children's Hospital (IU-RiCH)
Indianapolis, Indiana, 46202
Brian W Gray, MD, graybw@iupui.edu
- Recruiting
University of California-Irvine & Children's Hospital of Orange County (UC-CHOC)
Irvine, California, 92868
Yigit S Guner, MD, MS, YGuner@choc.org
- Recruiting
University of Arkansas & Arkansas Children's Hospital (UA-ACH)
Little Rock, Arkansas, 72202
Sid Dassinger, MD, dassingermelvins@uams.edu
- Recruiting
University of Southern California & Children's Hospital Los Angeles (USC-CHLA)
Los Angeles, California, 90027
Rachel Chapman, MD, rachapman@chla.usc.edu
- Recruiting
University of Louisville & Norton Children's Hospital (UL-NCH)
Louisville, Kentucky, 40202
Tiffany Wright, MD, tiffany.wright.1@louisville.edu
- Recruiting
University of Tennessee & LeBonheur Children's Hospital (UT-LBCH)
Memphis, Tennessee, 38105
Mark F Weems, MD, mweems@uthsc.edu
- Recruiting
Vanderbilt University & Vanderbilt University Medical Center (VUMC)
Nashville, Tennessee, 37232
Emily A Morris, MD, emily.a.morris@vumc.org
- Recruiting
Stanford University & Lucile Packard Children's Hospital (Stanford-LPCH)
Palo Alto, California, 94304
Krisa Van Meurs, MD, vanmeurs@stanford.edu
- Recruiting
Randall Children's Hospital-Portland (RCH)
Portland, Oregon, 97227
Cynthia Gindalewski, MD, cgingale@lhs.org
- Recruiting
University of Utah & Primary Children's Hospital (Utah-PCH)
Salt Lake City, Utah, 84108
Katie W Russell, MD, Katie.Russell@hsc.utah.edu
- Recruiting
University of California, San Diego & Rady Children's Hospital (UCSD-Rady)
San Diego, California, 92123
Denise Suttner, MD, dsuttner@rchsd.org
- Recruiting
University of Washington & Seattle Children's Hospital (UW-SCH)
Seattle, Washington, 98105
Rebecca Stark, MD, Rebecca.stark@seattlechildrens.org
About this study
Official title: Inhaled Nitric Oxide (iNO) for Congenital Diaphragmatic Hernia (CDH) - The "NoNO Trial" - a Multi-center, De-implementation, Stepped-wedge, Cluster-randomized Trial Within an Established Collaborative
The purpose of this study is to determine if de-implementation of inhaled nitric oxide (iNO) in the post-natal resuscitation/stabilization phase affects the composite outcome of extracorporeal life support (ECLS) use and/or mortality, as well as ECLS use, mortality, and/or oxygenation in congenital diaphragmatic hernia (CDH) newborns and to establish the cost-effectiveness of de-implementing iNO as a therapy in the postnatal resuscitation/stabilization phase of CDH management, which will be assessed as the incremental health system costs (savings) per prevented ECLS use and/or death.
Read the detailed description
In this multi-center study, centers will use iNO per their usual protocol, and centers will then crossover to iNO de-implementation (that is, at the time of crossover, centers will stop using iNO in the initial resuscitation period). A stepped-wedge crossover study design will be used, and the timing of crossover will be cluster randomized at the level of the center.
- Conditions
- Congenital Diaphragmatic Hernia
- Being tested
- Inhaled Nitric Oxide (iNO) use, De-implementation of Inhaled Nitric Oxide (iNO) use
- Keywords
- CDH, Inhaled Nitric Oxide, Pulmonary Hypertension
- Medical subject headings
- Hernias, Diaphragmatic, Congenital, Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inhaled Nitric Oxide (iNO) useDrug
The center will use iNO per their usual protocol in the initial resuscitation period (defined as birth through stabilization and CDH repair). No center will alter any component of their standard clinical practice guideline or protocol governing CDH care.
De-implementation of Inhaled Nitric Oxide (iNO) useOther
The center will stop using iNO in the initial resuscitation period (defined as birth through stabilization and CDH repair).
| Study group | Role | What they receive |
|---|---|---|
| Inhaled Nitric Oxide (iNO) use | Active comparator | The center will use iNO per their usual protocol in the initial resuscitation period (defined as birth through stabilization and CDH repair). No center will alter any component of their standard clinical practice guideline or protocol governing CDH care. Receives: Drug: Inhaled Nitric Oxide (iNO) use |
| De-implementation of Inhaled Nitric Oxide (iNO) use | Active comparator | The center will stop using iNO in the initial resuscitation period (defined as birth through stabilization and CDH repair). Receives: Other: De-implementation of Inhaled Nitric Oxide (iNO) use |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants who require Extracorporeal Life Support (ECLS) and/or who die prior to discharge
The primary outcome is the composite outcome of ECLS use and/or mortality.
Measured: from birth through hospital discharge (up to 12 months from birth)
Secondary outcomes (5)
Number of participants who require Extracorporeal Life Support (ECLS) prior to discharge
Measured: from birth through hospital discharge (up to 12 months from birth)
Number of participants who die prior to discharge
Measured: from birth through hospital discharge (up to 12 months from birth)
Change in oxygenation
For the iNO de-implementation arm, participants will be assessed 1 hour after the time when iNO would have been initiated, per the protocol of the center.
Measured: 1 hour after initiation of iNO use
Change in oxygenation
For the iNO de-implementation arm, participants will be assessed 6 hours after the time when iNO would have been initiated, per the protocol of the center.
Measured: 6 hours after initiation of iNO use
Total cost of initial inpatient care from birth through hospital discharge, per center
Measured: from birth through hospital discharge (up to 12 months from birth)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2022
- Study start1 Nov 2025
- Primary completion31 Oct 2030 (estimated)
- Study completion30 Apr 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Congenital Diaphragmatic HerniaStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center, HoustonThe 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- In this multi-center study, centers will use iNO per their usual protocol, and centers will then crossover to iNO de-implementation (that is, at the time of crossover, centers will stop using iNO in the initial resuscitation period). A stepped-wedge crossover study design will be used, and the timing of crossover will be cluster randomized at the level of the center.
- Masking
- None (open label)
- Enrolment
- 900 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- University of Tennessee & LeBonheur Children's Hospital (UT-LBCH), Children's Hospital of Orange County, Medical University of South Carolina Children's Health (MUSC), University of Michigan & CS Mott Children's Hospital (UM-CSMott), Randall Children's Hospital-Portland (RCH), Stanford University & Lucile Packard Children's Hospital (Stanford-LPCH), Rady Children's Hospital, San Diego, Boston Children's Hospital, Indiana University & Riley Children's Hospital (IU-RiCH), Norton Children's Hospital, University of Utah & Primary Children's Hospital (Utah-PCH), University of Washington & Seattle Children's Hospital (UW-SCH), University of Alabama & Children's Hospital of Alabama (UAB-CoA), University of Arkansas, Vanderbilt University Medical Center, University of Southern California & Children's Hospital Los Angeles (USC-CHLA), Emory University & Children's Healthcare of Atlanta (CHOA), Children's Hospital Colorado
- Responsible party
- Principal investigator, Matthew T Harting, The University of Texas Health Science Center, Houston
- Investigators
- Matthew Harting, MD, MS, FACS, Principal investigator, The University of Texas Health Science Center, Houston
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05213676
- Sponsor's protocol ID
- HSC-MS-21-0603
- Status last verified
- Oct 2026
- First submitted
- 27 Jan 2022
- Last updated
- 29 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhaled Nitric Oxide (iNO) for Congenital Diaphragmatic Hernia (CDH) - The "NoNO Trial" - a Multi-center, De-implementation, Stepped-wedge, Cluster-randomized Trial Within an Established Collaborative
- ClinicalTrials.gov ID
- NCT05213676
- Acronym / sponsor ID
- HSC-MS-21-0603
- Conditions
- Congenital Diaphragmatic Hernia
- Keywords
- CDH, Inhaled Nitric Oxide, Pulmonary Hypertension
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 900 participants (estimated)
- Lead sponsor
- The University of Texas Health Science Center, HoustonUniversity, hospital or other
- Collaborators
- University of Tennessee & LeBonheur Children's Hospital (UT-LBCH), Children's Hospital of Orange County, Medical University of South Carolina Children's Health (MUSC), University of Michigan & CS Mott Children's Hospital (UM-CSMott), Randall Children's Hospital-Portland (RCH), Stanford University & Lucile Packard Children's Hospital (Stanford-LPCH), Rady Children's Hospital, San Diego, Boston Children's Hospital, Indiana University & Riley Children's Hospital (IU-RiCH), Norton Children's Hospital, University of Utah & Primary Children's Hospital (Utah-PCH), University of Washington & Seattle Children's Hospital (UW-SCH), University of Alabama & Children's Hospital of Alabama (UAB-CoA), University of Arkansas, Vanderbilt University Medical Center, University of Southern California & Children's Hospital Los Angeles (USC-CHLA), Emory University & Children's Healthcare of Atlanta (CHOA), Children's Hospital Colorado
- Study start
- 1 Nov 2025 (actual)
- Primary completion
- 31 Oct 2030 (estimated)
- Study completion
- 30 Apr 2031 (estimated)
- First posted
- 28 Jan 2022 (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 purpose of this study is to determine if de-implementation of inhaled nitric oxide (iNO) in the post-natal resuscitation/stabilization phase affects the composite outcome of extracorporeal life support (ECLS) use and/or mortality, as well as ECLS use, mortality, and/or oxygenation in congenital diaphragmatic hernia (CDH) newborns and to establish the cost-effectiveness of de-implementing iNO as a therapy in the postnatal resuscitation/stabilization phase of CDH management, which will be assessed as the incremental health system costs (savings) per prevented ECLS use and/or death.
Detailed description
In this multi-center study, centers will use iNO per their usual protocol, and centers will then crossover to iNO de-implementation (that is, at the time of crossover, centers will stop using iNO in the initial resuscitation period). A stepped-wedge crossover study design will be used, and the timing of crossover will be cluster randomized at the level of the center.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- In this multi-center study, centers will use iNO per their usual protocol, and centers will then crossover to iNO de-implementation (that is, at the time of crossover, centers will stop using iNO in the initial resuscitation period). A stepped-wedge crossover study design will be used, and the timing of crossover will be cluster randomized at the level of the center.
| Arm | Type | Receives |
|---|---|---|
| Inhaled Nitric Oxide (iNO) use | Active comparator | Drug: Inhaled Nitric Oxide (iNO) useThe center will use iNO per their usual protocol in the initial resuscitation period (defined as birth through stabilization and CDH repair). No center will alter any component of their standard clinical practice guideline or protocol governing CDH care. |
| De-implementation of Inhaled Nitric Oxide (iNO) use | Active comparator | Other: De-implementation of Inhaled Nitric Oxide (iNO) useThe center will stop using iNO in the initial resuscitation period (defined as birth through stabilization and CDH repair). |
Who may qualify
- Ages
- 0 months to 1 month
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Postnatal, live born neonates with CDH
- Bochdalek hernia location (right or left)
- Diagnosed prior to 1 month of life
- Born within or transferred to (within 1 week of life) a CDHSG member center participating in the trial
Key exclusion criteria (4 listed)
- CDH diagnosis after 1 month of age
- Morgagni diaphragmatic hernia (central / anterior-medial diaphragmatic defect location)
- Transferred to a CDH Study Group (CDHSG) member center after 1 week of life
- Patients without potential access to iNO
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Inhaled Nitric Oxide (iNO) useThe center will use iNO per their usual protocol in the initial resuscitation period (defined as birth through stabilization and CDH repair). No center will alter any component of their standard clinical practice guideline or protocol governing CDH care. | Drug | Inhaled Nitric Oxide (iNO) use |
| De-implementation of Inhaled Nitric Oxide (iNO) useThe center will stop using iNO in the initial resuscitation period (defined as birth through stabilization and CDH repair). | Other | De-implementation of Inhaled Nitric Oxide (iNO) use |
Primary outcome
Number of participants who require Extracorporeal Life Support (ECLS) and/or who die prior to discharge
Time frame: from birth through hospital discharge (up to 12 months from birth)
The primary outcome is the composite outcome of ECLS use and/or mortality.
5 secondary outcomes
Number of participants who require Extracorporeal Life Support (ECLS) prior to discharge
Time frame: from birth through hospital discharge (up to 12 months from birth)
Number of participants who die prior to discharge
Time frame: from birth through hospital discharge (up to 12 months from birth)
Change in oxygenation
Time frame: 1 hour after initiation of iNO use
Change in oxygenation
Time frame: 6 hours after initiation of iNO use
Total cost of initial inpatient care from birth through hospital discharge, per center
Time frame: from birth through hospital discharge (up to 12 months from birth)
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 29 Oct 2026.
- Individual participant dataSharing planned: No
Related trials for Congenital Diaphragmatic Hernia
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Congenital Diaphragmatic Hernia, Pulmonary Hypoplasia
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Effect of a Parenteral Emulsion With Omega3 on Neonates With PPHN and CDH
Pulmonary Hypertension of Newborn, Diaphragm Defect
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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.
Matthew Harting, MD, MS, FACS principal investigator
The University of Texas Health Science Center, Houston
19 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Inhaled Nitric Oxide (iNO) use and De-implementation of Inhaled Nitric Oxide (iNO) use in people with Congenital Diaphragmatic Hernia, run by The University of Texas Health Science Center, Houston at 19 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 5 inclusion and 4 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 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Matthew Harting, MD, MS, FACS ((713) 500-7398, Matthew.T.Harting@uth.tmc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants who require Extracorporeal Life Support (ECLS) and/or who die prior to discharge (time frame: from birth through hospital discharge (up to 12 months from birth)). 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 29 Oct 2026.