Predictors of Inhaled Nitric Oxide Responsiveness in Patients With PPHN (PINOR)

Predictors of Inhaled Nitric Oxide (iNO) Responsiveness in Neonates With Persistent Pulmonary Hypertension of the Newborn (PPHN)/Hypoxic Respiratory Failure (HRF)

To identify biochemical, clinical, or genetic biomarkers that may predict responsiveness to iNO in neonates with PPHN/HRF. The primary outcome will be identification of any biomarker(s) associated with response to iNO therapy. We will evaluate related biomarkers at various time-points during disease progression and in response to therapy, including single nucleotide polymorphisms in the cyclic adenosine monophosphate/cyclic guanosine monophosphate-Phosphodiesterase (PDE) pathway, indicators of metabolic dysregulation and inflammation, as well as biochemical markers of heart strain. We will perform targeted neonatal echocardiograms to evaluate severity of PPHN and heart function both as an added clinical biomarker and to follow disease progression.

Study Overview

• Status: Withdrawn
• Conditions: Hypoxic Respiratory Failure; PPHN

Detailed Description

A single-center, prospective observational cohort study evaluating potential biochemical, clinical, and/or genetic biomarkers in neonates admitted with a diagnosis of PPHN that may predict iNO response. Thus, it is important to collect data prior to the initiation of iNO to be able to identify biomarkers that can predict response. For patients who meet the screening criteria and when consent is not attainable prior to initiation of the potential life-saving iNO therapy, then samples will be obtained with deferred written informed parental consent obtained within the first 4 hours after enrollment. These patients will have one sample of blood, urine, and tracheal aspirate (if available) collected. If the patient meets the inclusion and exclusion criteria, the patient will be recruited for study participation. To ensure no delay in care or in the initiation of the only FDA-approved vasodilator for this population, iNO, a deferred written informed parental consent is requested to allow for the collection of blood, urine, tracheal aspirate specimens (if available) prior to the initiation of iNO. Only one sample of blood and tracheal aspirate specimens will be collected prior to the deferred consent. Samples are often collected during the routine collections that are obtain from patients who are critically ill such as in our study participants, therefore, no additional discomfort will be expected from this study. Urine collection will be from cotton ball collection that would normally be discarded and is noninvasive. All data and biospecimens obtained from eligible infants whose parent(s) decline consent or do not qualify for the study will be discarded.

• Study Type: Observational

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Late pre-term and term neonates admitted to NCH NICU with a diagnosis of PPHN/HRF.

Description

Inclusion Criteria:

1. Greater than 34 weeks gestational age.
2. Less than or equal to 10 postnatal days of age.
3. Echocardiographic evidence of PPHN (right-to-left or bidirectional shunt at the foramen ovale or the ductus arteriosus and/or severe tricuspid regurgitation)

Exclusion Criteria:

1. Lethal congenital anomalies, obvious syndromic or chromosomal disorders.
2. Congenital diaphragmatic hernia.
3. Congenital heart defect (except a small atrial septal defect, ventricular septal defect, and/or PDA).

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarker Identification	Identification of a biomarker that is associated with response to iNO therapy	24 hours after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarker Predication	Identification of a biomarker that may be predictive of the need for iNO therapy	24 hours after enrollment

Collaborators and Investigators

• Sponsor: Nationwide Children's Hospital
• Investigators: Principal Investigator: Bernadette Chen, MD, Nationwide Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2021
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: September 12, 2023
• First Submitted That Met QC Criteria: September 12, 2023
• First Posted (Actual): September 21, 2023

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 12, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Respiratory Insufficiency; Hypoxia
• Other Study ID Numbers: IRB18-00711

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: No
• Studies a U.S. FDA-regulated device product: No