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 Identifier: NCT05213676
• Recruitment Status: Not yet recruiting
• First Posted: January 28, 2022
• Last Update Posted: January 28, 2022
• Sponsor: The University of Texas Health Science Center, Houston
• Information provided by (Responsible Party): Matthew Tihen Harting, The University of Texas Health Science Center, Houston

Tracking Information

• First Submitted Date: January 27, 2022
• First Posted Date: January 28, 2022
• Last Update Posted Date: January 28, 2022
• Estimated Study Start Date: January 1, 2023
• Estimated Primary Completion Date: January 30, 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 27, 2022)

Number of participants that require Extracorporeal Life Support (ECLS) and/or that die prior to discharge [ Time Frame: from birth through hospital discharge (upto 12 months from birth) ]

The primary outcome is the composite outcome of ECLS use and/or mortality.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: January 27, 2022)

• Number of participants that require Extracorporeal Life Support (ECLS) prior to discharge [ Time Frame: from birth through hospital discharge (upto 12 months from birth) ]
• Number of participants that die prior to discharge [ Time Frame: from birth through hospital discharge (upto 12 months from birth) ]
• 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.
• 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.
• Total cost of initial inpatient care from birth through hospital discharge, per center [ Time Frame: from birth through hospital discharge (upto 12 months from birth) ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief 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
• 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
• Brief Summary: The purpose of this study is to Determine if deimplementation of iNO in the post-natal resuscitation/stabilization phase affects the composite outcome of ECLS use and/or mortality, as well as ECLS use, mortality, and/or oxygenation in CDH newborns and to establish the cost-effectiveness of deimplementing 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 Type: Interventional
• Study Phase: Phase 4

Study Design

Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:

In this multi-center study, centers will use iNO per their usual protocol, and centers will then crossover to iNO deimplementation (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)
Primary Purpose: Treatment

• Condition: Congenital Diaphragmatic Hernia

Intervention

• 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.
• 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).

Study Arms

• 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.
  Intervention: Drug: Inhaled Nitric Oxide (iNO) use
• 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).
  Intervention: Other: De-implementation of Inhaled Nitric Oxide (iNO) use

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: January 27, 2022): 600
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 30, 2028
• Estimated Primary Completion Date: January 30, 2028 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 0 Months to 1 Month (Child)
• Accepts Healthy Volunteers: No

Contacts

Contact: Matthew Harting, MD, MS, FACS; (713) 500-7398; Matthew.T.Harting@uth.tmc.edu

Contact: Ashley Ebanks; (832) 325-7234; Ashley.Harmon@uth.tmc.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05213676
• Other Study ID Numbers: HSC-MS-21-0603
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Matthew Tihen Harting, The University of Texas Health Science Center, Houston
• Original Responsible Party: Same as current
• Current Study Sponsor: The University of Texas Health Science Center, Houston
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: The University of Texas Health Science Center, Houston
• Verification Date: January 2022