Clinical trial NCT04938167: Preductal Oxygen Saturation Target in Term and Late Preterm Neonates With Hypoxemic Respiratory Failure or Pulmonary Hypertension
Official title: Preductal Oxygen Saturation Target in Term and Late Preterm Neonates With Hypoxemic Respiratory Failure or Pulmonary Hypertension (POST-IT)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Persistent Pulmonary Hypertension of the Newborn
Hypoxemic Respiratory Failure
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Center for Advancing Translational Sciences (NCATS)
First posted: 2021-06-24
Enrollment: 54
Sex: ALL
Minimum age (years): 0
Maximum age (years): 28
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized assignment to Standard arm (target preductal SpO2 91% to 95%) or Intervention arm (target preductal SpO2 95% to 99%)
Primary purpose: TREATMENT

Brief summary: The purpose of this research is to evaluate two oxygen saturation goals for newborns with pulmonary hypertension. Participation in this research will involve random assignment to one of two oxygen saturation goals, review of the medical record and targeted echocardiograms.

Detailed description: Successful transition at birth is dependent on establishment of lungs as the organ of gas exchange. Breathing at birth and an increase in alveolar oxygen tension (PAO2) leads to an 8-10 fold increase in pulmonary blood flow with a marked reduction in pulmonary vascular resistance (PVR). Failure to decrease PVR at birth results in hypoxemic respiratory failure (HRF) and persistent pulmonary hypertension of the newborn (PPHN). Hypoxemia exacerbates PPHN by increasing PVR. However, administration of excess oxygen in animal studies has been shown to increase free radical formation and reduce response to pulmonary vasodilators such as inhaled nitric oxide (iNO).

Thus, there is potential for benefit and also poor outcomes at both higher and lower oxygen saturations (SpO2), with the ideal range being unknown. The investigators will conduct a randomized unblinded, pilot trial to compare two ranges of target preductal SpO2 in late preterm and term infants with HRF or PPHN. During this trial the investigators will assess the reliability of a hypoxic respiratory failure/pulmonary hypertension (HRF/PH) score that could then be used in a larger clinical trial. The investigators will also assess trial feasibility and obtain preliminary estimates of outcomes. Our central hypothesis is that neonates with pulmonary hypertension (PH) and/or HRF, targeting preductal SpO2 of 95-99% (intervention) will result in lower PVR and lower need for non-oxygen based pulmonary vasodilators (iNO, milrinone and sildenafil) compared to a target of 91-95% (standard).

Eligibility criteria: Inclusion Criteria:

* Corrected gestational age (postmenstrual age) \> 34 6/7 weeks
* postnatal age ≤ 28 d
* on respiratory support with invasive mechanical ventilation, non-invasive ventilation, CPAP or high flow nasal cannula (defined as flow rates ≥ 2 LPM with a humidifier), inspired oxygen concentration, FiO2 ≥ 0.3
* and echocardiography shows any finding suggestive of PH (or score \> 0 for PH in table 2).
* Infants with congenital diaphragmatic hernia (CDH), Down syndrome, hypoxic ischemic encephalopathy (HIE) on therapeutic hypothermia and patent ductus arteriosus (PDA), patent foramen ovale/atrial septal defect (PFO/ASD) and ventricular septal defect (VSD) (single or multiple) \< 2 mm can be included in the study.

Exclusion Criteria:

* \< 32 weeks gestation at birth (31 6/7 or lower)
* Weight \< 2000 g at the time of enrollment
* Severe HRF with OI \> 35 or SpO2 \< 75% on FiO2 = 1.0 on mechanical ventilation for \> 60 minutes in spite of correction of reversible factors such as pneumothorax
* A condition or congenital anomaly known to be lethal (high likelihood of death during infancy) - e.g., trisomy 18 or trisomy 13
* Congenital heart disease other than ASD/PFO, PDA or VSD (single or multiple defects) \< 2 mm.

Primary outcomes:
measure: Hypoxemic Respiratory Failure and Pulmonary Hypertension (HRF/PH) score
timeFrame: At enrollment
measure: Correlation of the Oxygenation and Echocardiography components of the HRF/PH scores
timeFrame: At enrollment
Secondary outcomes:
measure: Intracluster correlation coefficients of the HRF/PH score
timeFrame: Days 3-7
measure: Preliminary estimates of intervention effects on outcomes (length of stay, duration of mechanical ventilation, and ECMO)
timeFrame: Day 7
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California-Davis
state: California
Study officials:
References:
citation: Siefkes H, Sunderji S, Vaughn J, Sankaran D, Vali P, Vadlaputi P, Timberline S, Bhatt A, Tancredi D, Lakshminrusimha S. Factors to Consider to Study Preductal Oxygen Saturation Targets in Neonatal Pulmonary Hypertension. Children (Basel). 2022 Mar 11;9(3):396. doi: 10.3390/children9030396.