De-implementing Inhaled Nitric Oxide for Congenital Diaphragmatic Hernia

February 4, 2026 updated by: Matthew T Harting, The University of Texas Health Science Center, Houston

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

600

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
    • Arkansas
      • Little Rock, Arkansas, United States, 72202
        • Recruiting
        • University of Arkansas & Arkansas Children's Hospital (UA-ACH)
        • Contact:
    • California
      • Irvine, California, United States, 92868
        • Recruiting
        • University of California-Irvine & Children's Hospital of Orange County (UC-CHOC)
        • Contact:
      • Los Angeles, California, United States, 90027
        • Recruiting
        • University of Southern California & Children's Hospital Los Angeles (USC-CHLA)
        • Contact:
      • Palo Alto, California, United States, 94304
        • Recruiting
        • Stanford University & Lucile Packard Children's Hospital (Stanford-LPCH)
        • Contact:
      • San Diego, California, United States, 92123
        • Recruiting
        • University of California, San Diego & Rady Children's Hospital (UCSD-Rady)
        • Contact:
    • Colorado
      • Aurora, Colorado, United States, 80045
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University & Children's Healthcare of Atlanta (CHOA)
        • Contact:
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Indiana University & Riley Children's Hospital (IU-RiCH)
        • Contact:
    • Kentucky
      • Louisville, Kentucky, United States, 40202
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan & CS Mott Children's Hospital (UM-CSMott)
        • Contact:
    • Oregon
      • Portland, Oregon, United States, 97227
        • Recruiting
        • Randall Children's Hospital-Portland (RCH)
        • Contact:
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Recruiting
        • Medical University of South Carolina Children's Health (MUSC)
        • Contact:
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • Recruiting
        • University of Tennessee & LeBonheur Children's Hospital (UT-LBCH)
        • Contact:
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt University & Vanderbilt University Medical Center (VUMC)
        • Contact:
    • Texas
      • Houston, Texas, United States, 77030
    • Utah
      • Salt Lake City, Utah, United States, 84108
        • Recruiting
        • University of Utah & Primary Children's Hospital (Utah-PCH)
        • Contact:
    • Washington
      • Seattle, Washington, United States, 98105

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 second to 1 month (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Postnatal, live born neonates with CDH

    a. 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Inhaled Nitric Oxide (iNO) use
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.
Drug: Inhaled Nitric Oxide (iNO) use
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.
Active Comparator: De-implementation of Inhaled Nitric Oxide (iNO) use
The 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
The center will stop using iNO in the initial resuscitation period (defined as birth through stabilization and CDH repair).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
from birth through hospital discharge (up to 12 months from birth)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in oxygenation
Time Frame: 1 hour after initiation of iNO use
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.
1 hour after initiation of iNO use
Change in oxygenation
Time Frame: 6 hours after initiation of iNO use
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.
6 hours after initiation of iNO use
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)
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)
from birth through hospital discharge (up to 12 months from birth)
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)
from birth through hospital discharge (up to 12 months from birth)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Texas Health Science Center, Houston

Collaborators

University of Tennessee & LeBonheur Children's Hospital (UT-LBCH)
University of California-Irvine & Children's Hospital of Orange County (UC-CHOC)
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)
University of California, San Diego & Rady Children's Hospital (UCSD-Rady)
Harvard University & Boston Children's Hospital (Harvard-BCH)
Indiana University & Riley Children's Hospital (IU-RiCH)
University of Louisville & Norton Children's Hospital (UL-NCH)
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 & Arkansas Children's Hospital (UA-ACH)
Vanderbilt University & Vanderbilt University Medical Center (VUMC)
University of Southern California & Children's Hospital Los Angeles (USC-CHLA)
Emory University & Children's Healthcare of Atlanta (CHOA)
University of Colorado & Children's Hospital of Colorado (CU-CHC)

Investigators

  • Principal Investigator: Matthew Harting, MD, MS, FACS, The University of Texas Health Science Center, Houston

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2025

Primary Completion (Estimated)

October 31, 2030

Study Completion (Estimated)

April 30, 2031

Study Registration Dates

First Submitted

January 27, 2022

First Submitted That Met QC Criteria

January 27, 2022

First Posted (Actual)

January 28, 2022

Study Record Updates

Last Update Posted (Actual)

February 9, 2026

Last Update Submitted That Met QC Criteria

February 4, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HSC-MS-21-0603

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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