Clinical trial NCT06043635: Predictors of Inhaled Nitric Oxide Responsiveness in Patients With PPHN
Official title: Predictors of Inhaled Nitric Oxide (iNO) Responsiveness in Neonates With Persistent Pulmonary Hypertension of the Newborn (PPHN)/Hypoxic Respiratory Failure (HRF)
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: PPHN
Hypoxic Respiratory Failure
Lead sponsor: Nationwide Children's Hospital
Sponsor class: OTHER
First posted: 2023-09-21
Enrollment: 0
Sex: ALL
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Late pre-term and term neonates admitted to NCH NICU with a diagnosis of PPHN/HRF.

Brief summary: 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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Biomarker Identification
timeFrame: 24 hours after enrollment
Secondary outcomes:
measure: Biomarker Predication
timeFrame: 24 hours after enrollment
Other outcomes:
Locations:
Study officials:
affiliation: Nationwide Children's Hospital
name: Bernadette Chen, MD
role: PRINCIPAL_INVESTIGATOR
References: