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 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.

Study Overview

• Status: Not yet recruiting
• Conditions: Congenital Diaphragmatic Hernia
• Intervention / Treatment: Drug: Inhaled Nitric Oxide (iNO) use; Other: De-implementation of Inhaled Nitric Oxide (iNO) use

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

• Study Contact: Name: Matthew Harting, MD, MS, FACS; Phone Number: (713) 500-7398; Email: Matthew.T.Harting@uth.tmc.edu
• Study Contact Backup: Name: Ashley Ebanks; Phone Number: (832) 325-7234; Email: Ashley.Harmon@uth.tmc.edu

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas health Science Center at Houston
      • Contact: Ashley Ebanks; Phone Number: (832) 325-7234; Email: Ashley.Harmon@uth.tmc.edu
      • Contact: Matthew Harting, MD, MS, FACS; Phone Number: 713-500-7398; Email: Matthew.T.Harting@uth.tmc.edu

Participation Criteria

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

How is the study designed?

Design Details

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

Number of Arms

2

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 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)

Collaborators and Investigators

• Sponsor: 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 record dates

Study Major Dates

• Study Start (Estimated): January 1, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2030

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): June 29, 2023
• Last Update Submitted That Met QC Criteria: June 27, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Pulmonary hypertension; Inhaled Nitric Oxide; CDH
• Additional Relevant MeSH Terms: Congenital Abnormalities; Pathological Conditions, Anatomical; Internal Hernia; Hernia; Hernias, Diaphragmatic, Congenital; Hernia, Diaphragmatic; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antioxidants; Free Radical Scavengers; Endothelium-Dependent Relaxing Factors; Gasotransmitters; Nitric Oxide
• 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