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

N/ANot Yet RecruitingNCT07837921

Novlead Inc.50 enrolled

Overview

* Title : A multicenter clinical trial of the portable nitric oxide generation and delivery system (INOwill N200) for the treatment of neonatal hypoxic respiratory failure complicated by pulmonary hypertension * Investigational product :Device Name: Nitric Oxide Generator and Delivery System * Study population : Newborn Babies ≥34 weeks of gestation and postnatal age \<30 days with breathing problems associated with pulmonary hypertension (high blood pressure in the lungs). The goal of this prospective, multicenter, single-arm, post-market clinical study is to evaluate the performance, safety, usability, and medico-economic aspects of the INOwill-N200 device when used to deliver inhaled nitric oxide (iNO) to neonates requiring iNO therapy as part of their clinical care. The main questions this study aims to answer are: * Can the INOwill-N200 deliver the prescribed NO concentration and maintain delivered NO and NO₂ concentrations within the manufacturer-specified performance and safety ranges? * Does oxygenation improve 60 minutes after initiation of iNO therapy compared with baseline, as assessed by changes in the Oxygenation Index and arterial oxygen partial pressure? * What adverse events, serious adverse events, device deficiencies, alarms, or interruptions occur during treatment? * How do healthcare professionals assess the performance and usability of the device? * What are the total cost per participant and the cost per day of iNO therapy using the INOwill-N200? There is no comparison group in this study. The decision to initiate, adjust, wean, interrupt, or discontinue iNO therapy will remain under the responsibility of the treating medical team and will be based on each participant's clinical condition. Neonates enrolled in the study will: * Receive prescribed iNO therapy using the INOwill-N200; * Undergo oxygenation and ventilation assessments at baseline, 60 minutes, 6 hours, 24 hours, and at the end of iNO treatment, as specified in the protocol; * Have delivered NO, NO₂, and oxygen concentrations monitored during treatment; * Have methemoglobin levels monitored according to the study protocol; * Be monitored for adverse events, serious adverse events, device deficiencies, alarms, and treatment interruptions; * Be followed until the end of study participation, for up to 14 days. Healthcare professionals using the INOwill-N200 will complete the iNO Device Performance Assessment Questionnaire to evaluate device performance, usability, and overall satisfaction. Device use and healthcare resource consumption will also be collected to estimate the total cost of iNO treatment per participant and the cost per day of therapy.

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.

Eligibility

Sex: ALLMin age: 0 DaysMax age: 30 Days

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Evaluate the performance of the INOwill-N200 by measuring the proportion of participants achieving a reduction ≥20% in the Oxygenation Index (OI) after 60 minutes of iNO therapy compared to baseline.

OI is calculated as following: OI = (PaO2\*FiO2\*100)/PaO2

Time frame: Comparision between OI at baseline and OI after 60 minutes of iNO therapy.

Secondary Outcomes

To assess the clinical performance of the INOwill-N200 under real-world conditions by measuring the Oxygen Saturation Index (OSI) at predefined time points after baseline.

Description of Oxygen Saturation Index (OSI) during iNO treatment in neonates with PPHN, using continuous oxygenation metrics measured at predefined after baseline (60 min, 6 hours, 12 hours, 24 hours, and daily until treatment discontinuation or at day 14)

Time frame: Measures performed at 60 min, 6 hours, 12 hours, 24 hours, and daily until treatment discontinuation or maximum at day 14, after treatment initiation.

To assess the clinical performance of the INOwill-N200 under real-world conditions by measuring the partial pressure of oxygen in arterial blood (PaO₂) at predefined time points after baseline.

Description of the partial pressure of oxygen in arterial blood (PaO₂) during iNO treatment in neonates with PPHN, using continuous oxygenation metrics measured at predefined time points after baseline

Time frame: Measures performed at 60 min, 6 hours, 12 hours, 24 hours, and daily until treatment discontinuation or maximum at day 14, after treatment initiation.

To assess the clinical performance of the INOwill-N200 under real-world conditions by measuring the PF ratio (PaO₂/FiO₂) at predefined time points after baseline.

Description of the PF ratio (PaO₂/FiO₂) during iNO treatment in neonates with PPHN, using continuous oxygenation metrics measured at predefined time points after baseline (60 min, 6 hours, 12 hours, 24 hours, and daily until treatment discontinuation or at day 14)

Time frame: Measures performed at 60 min, 6 hours, 12 hours, 24 hours, and daily until treatment discontinuation or maximum at day 14, after treatment initiation.

To assess the clinical performance of the INOwill-N200 under real-world conditions by measuring the SF ratio (SpO₂/FiO₂) at predefined time points after baseline.

Description of the SF ratio (SpO₂/FiO₂) during iNO treatment in neonates with PPHN, using continuous oxygenation metrics measured at predefined time points after baseline (60 min, 6 hours, 12 hours, 24 hours, and daily until treatment discontinuation or at day 14)

Time frame: Up to day 14

To assess the clinical effectiveness of the INOwill-N200 by measuring the proportion of participants requiring extracorporeal membrane oxygenation (ECMO) rescue 14 days after iNO initiation

proportion of participants requiring extracorporeal membrane oxygenation (ECMO) rescue during hospitalization

Time frame: At hospital discharge

To assess the accuracy of delivered NO by comparing the concentration delivered by the device with the prescribed NO concentration during the treatment period with a maximum of 14 days

Accuracy of delivered NO concentration compared with prescribed NO concentration

Time frame: At baseline, 60 minutes, 6 hours, 24 hours after treatment initiation and at the end of inhaled nitric oxide treatment with a maximum of 14 days.

To assess the stability of NO delivery by measuring the Number of treatment interruptions during the treatment period with a maximum of 14 days

Stability of NO delivery measured by the number of treatment interruptions

Time frame: From treatment initiation until the end of iNO treatment with a maximum of 14 days.

To assess the time required to reach the prescribed NO Concentration

Time to reach the targeted iNO concentration delivered by the INOwill-N200 after treatment initiation

Time frame: From treatment initiation until the end of iNO treatment with a maximum of 14 days.

To describe any adverse events, whether related to the use of INOwill N200 T

Rate of adverse events and serious adverse events related or not to the device; Rate of device deficiencies (nature, severity, and resolution of device deficiencies) Frequency of technical malfunctions (alarm activations, unplanned interruptions, and others) of NO delivery.

Time frame: From initiation of iNO therapy through the end of the study participation (up to Day 14)

To assess the safety of the INOwill-N200 by measuring the number of participants with methemoglobinemia during the iNO treatment period in accordance with routine clinical practice at each participating site

Proportion of participants with Methemoglobin concentration ≥5%, requiring reassessment of iNO therapy

Time frame: From initiation of iNO therapy through its final discontinuation (up to Day 14).

To assess clinicians' satisfaction with the use of the INOwill N200

Overall investigator satisfaction scores based on iNO Device Performance Assessment Questionnaire

Time frame: Initiation and at the end of iNO treatment or at the end of study participation (up to Day 14)

To estimate the cost of iNO treatment per patient