Post Market Clinical Follow-up to Assess the Portable Nitric Oxide Generation and Delivery System (INOwill N200) for the Treatment of Neonatal Hypoxic Respiratory Failure Complicated by Pulmonary Hypertension

This multicenter clinical study will evaluate the INOwill-N200 nitric oxide generation and delivery system in neonates with hypoxic respiratory failure associated with pulmonary hypertension who require inhaled nitric oxide therapy.

Decisions regarding the prescribed iNO concentration, dose adjustment, weaning, interruption, and discontinuation will be made by the treating medical team according to the participant's clinical condition and the study protocol.

Technical performance will be assessed using treatment data including prescribed and delivered NO concentrations, delivered NO₂ and oxygen concentrations, the time required to reach the prescribed NO concentration, the stability of NO delivery, alarms, treatment interruptions, and device or accessory replacements. Where sufficiently detailed timestamped data are available, the percentage of valid monitored treatment time during which NO and NO₂ concentrations remain within the manufacturer-specified performance and safety ranges will be calculated centrally.

Oxygenation and ventilation parameters will be assessed at baseline, 60 minutes, 6 hours, 12 hours, 24 hours, and daily thereafter through Day 14, as applicable. Collected parameters include the Oxygenation Index, Oxygen Saturation Index, PaO₂, SpO₂, FiO₂, PaO₂/FiO₂ ratio, SpO₂/FiO₂ ratio, ventilation mode, and other protocol-defined respiratory parameters. Actual assessment dates and times will be recorded to evaluate compliance with the predefined assessment windows.

Safety surveillance will include adverse events, serious adverse events, device deficiencies, technical malfunctions, alarms, unplanned interruptions of NO delivery, and methemoglobin concentrations. The seriousness, severity, outcome, and relationship of each event to the INOwill-N200, iNO therapy, and study procedures will be assessed as defined in the protocol.

Healthcare professionals will complete the iNO Device Performance Assessment Questionnaire at baseline and on Day 14.

Device-use and healthcare-resource data will be collected to support the medico-economic evaluation. Treatment duration, generator use, accessories, consumables, replacements, staff time, and technical interventions may be combined with predefined unit costs to estimate the direct cost of iNO treatment per participant and the cost per treatment day.

Inclusion criteria

• Gestational age ≥34 weeks;
• Postnatal age ≤30 days at iNO initiation;
• Pulmonary hypertension confirmed by echocardiography (this includes any ultrasound sign or measurement consistent with pulmonary hypertension)
• Diagnosis of hypoxic respiratory failure requiring invasive, with any mode (either conventional mechanical ventilation or high-frequency ventilation)
• Oxygenation impairment despite optimized respiratory support, defined by at least one of the following:

Oxygenation Index (OI) ≥20; FiO₂ requirement ≥0.60 pour avoir preductal SpO₂ >90%; PaO₂ <60 mmHg despite optimized ventilatory support;

• Written informed consent will be obtained prior to inclusion from both parents whenever possible or, where this is not feasible, from one parent holding parental responsibility in accordance with applicable national laws and regulations and the other will be informed as soon as possible.
• If the mother is temporarily unable to provide written informed consent, her oral consent will be obtained in the presence of an impartial witness and appropriately documented. Her written informed consent will then be obtained as soon as she is able to provide it.
• Prospective informed consent may be obtained from mothers with threatened preterm labor when there is a high likelihood that their newborn may subsequently require treatment with inhaled nitric oxide (iNO).
• Be affiliated to French social security system.

Exclusion criteria

• Suspected pulmonary hypoplasia is considered by the investigator to be the primary cause of hypoxemic respiratory failure.
• Congenital heart defects (other than a small, hemodynamically insignificant patent ductus arteriosus, or a ventricular septal defect or a patent foramen ovale)
• Undergoing or expected to need a combination of other pulmonary vasodilators or surfactants
• Methemoglobinemia (MetHb >2.5%) before the onset of iNO treatment
• Need for immediate cardio-pulmonary resuscitation (i.e. terminal conditions)
• Any condition that, in the investigator's judgment, makes the infant unsuitable for participation in this clinical trial