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

• Sponsor: The University of Texas Health Science Center, Houston (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05213676
• Collaborator: (none)
• Enrollment: 600
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 60.9
• Patients Per Site Per Month: 9.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Congenital Diaphragmatic Hernia	Drug: Inhaled Nitric Oxide (iNO) use; Other: De-implementation of Inhaled Nitric Oxide (iNO) use	Phase 4

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

• Study Type: Interventional
• Anticipated Enrollment: 600 participants
• 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.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
• 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
• Anticipated Study Start Date: Jan 1, 2023
• Anticipated Primary Completion Date: Jan 30, 2028
• Anticipated Study Completion Date: Jan 30, 2028

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures

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

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

Secondary Outcome Measures

1. Number of participants that require Extracorporeal Life Support (ECLS) prior to discharge [from birth through hospital discharge (upto 12 months from birth)]

2. Number of participants that die prior to discharge [from birth through hospital discharge (upto 12 months from birth)]

3. Change in oxygenation [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.

4. Change in oxygenation [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.

5. Total cost of initial inpatient care from birth through hospital discharge, per center [from birth through hospital discharge (upto 12 months from birth)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 0 Months to 1 Month
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Postnatal, live born neonates with CDH

1. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Texas Health Science Center at Houston	Houston	Texas	United States	77030

Sponsors and Collaborators

• The University of Texas Health Science Center, Houston

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Matthew Tihen Harting, Associate Professor, The University of Texas Health Science Center, Houston
• ClinicalTrials.gov Identifier: NCT05213676
• Other Study ID Numbers: HSC-MS-21-0603
• First Posted: Jan 28, 2022
• Last Update Posted: Jan 28, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Keywords provided by Matthew Tihen Harting, Associate Professor, The University of Texas Health Science Center, Houston: CDH; Inhaled Nitric Oxide; Pulmonary hypertension
• Additional relevant MeSH terms: Hernias, Diaphragmatic, Congenital; Hernia; Hernia, Diaphragmatic; Nitric Oxide

Study Results

No Results Posted as of Jan 28, 2022