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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Congenital Diaphragmatic Hernia

Intervention / Treatment
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* Drug: Inhaled Nitric Oxide (iNO) use
* Other: De-implementation of Inhaled Nitric Oxide (iNO) use


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 0 Months
Maximum Age: 1 Month

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional 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)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants that require Extracorporeal Life Support (ECLS) and/or that die prior to discharge | The primary outcome is the composite outcome of ECLS use and/or mortality. | from birth through hospital discharge (upto 12 months from birth) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants that require Extracorporeal Life Support (ECLS) prior to discharge |  | from birth through hospital discharge (upto 12 months from birth) | 
| Number of participants that die prior to discharge |  | from birth through hospital discharge (upto 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. | 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. | 6 hours after initiation of iNO use | 
| Total cost of initial inpatient care from birth through hospital discharge, per center |  | from birth through hospital discharge (upto 12 months from birth) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CDH, Inhaled Nitric Oxide, Pulmonary hypertension