Assessment of Persistent Pulmonary Hypertension Incidence in Neonates with Respiratory Failure Treated with Salbutamol Sulfate and Sodium Chloride

The primary objective of this study is the **assessment** of the frequency of occurrence of persistent pulmonary hypertension of the newborn (PPHN). This condition is defined by the necessity to use ventilation with an additional oxygen fraction in the respiratory mixture (FiO2) greater than 0.30, alongside echocardiographic features indicating increased pulmonary pressure, such as right-left or bi-directional leakage through an unobstructed arterial duct or oval opening, or a difference in pre- and post-ductal saturation exceeding 10%. The clinical relevance of this objective lies in its potential to improve the understanding and management of PPHN, a serious condition that can lead to significant morbidity in newborns.

Secondary objectives include the evaluation of the TTN scale (modified Silverman score) in comparison to the concentration of oxygen used during ventilation and the parameters of acid-base equilibrium, specifically pH, carbon dioxide pressure (pCO2), and base excess (BE) in the compared groups. These secondary objectives aim to provide further insights into the respiratory and metabolic status of newborns undergoing treatment, which could inform therapeutic strategies and improve clinical outcomes.

The clinical trial focuses on **breathing disorders** as a cause of neonatal respiratory failure. The study population comprises newborns, both male and female, born from pregnancies lasting between 32 0/7 and 41 6/7 weeks. The trial includes a vulnerable population, as it involves newborns who may require breathing support shortly after birth. The sponsor has not provided the total number of participants. Participants were selected based on specific criteria, including disturbances of tachypnoe breathing and expiratory bulking persisting for more than 15 minutes after birth or occurring up to the age of 6 hours, and the need for breathing support at birth before the age of 6 hours. Additionally, a chest X-ray must be taken within 6 hours of age, and an acid-base balance test must be performed from umbilical cord blood or capillary blood drawn from the heel of a newborn in the first hour of life. The trial does not specify any particular lifestyle considerations such as diet or physical activity, as the focus is on the immediate postnatal period.

The clinical trial is designed to evaluate the frequency of persistent pulmonary hypertension of the newborn (PPHN) in neonates born between 32 and 42 weeks of gestation, treated with **salbutamol sulfate**. This is a Phase III, randomized, double-blind, controlled study, with an estimated trial duration from November 15, 2021, to December 31, 2025. The trial involves the administration of **salbutamol sulfate** via inhalation, with **sodium chloride** serving as a placebo. The primary objective is to assess the incidence of PPHN, defined by the need for ventilation with an additional oxygen fraction (FiO2) greater than 0.30 and echocardiographic features of increased pulmonary pressure or a significant difference in pre- and post-ductal saturation.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on specific inclusion criteria, such as gestational age and respiratory conditions. The inclusion criteria require newborns to exhibit respiratory disturbances persisting for more than 15 minutes after birth or the need for breathing support within the first six hours of life. A chest X-ray and acid-base balance test are also required within the first six hours. Follow-up visits will monitor the primary and secondary endpoints, including the TTN score, need for intubation, duration of respiratory support, hospitalization time, and occurrence of adverse events. The end-of-study visit will conclude the participant's involvement, which is expected to last up to two weeks, depending on the treatment period and individual response.

Participants may be withdrawn from the study if they experience significant adverse events, fail to comply with the study protocol, or if the investigator deems it necessary for their safety. The trial's design ensures rigorous monitoring and data collection to achieve its objectives while maintaining participant safety and scientific integrity.

The clinical trial involves the administration of **salbutamol sulfate**, a chemical compound used as the experimental medication. The pharmaceutical form of salbutamol sulfate is designated as PHF00207MIG, and it is administered via **inhalation**. The trial does not specify a maximum daily dose or total dose amount, indicating that the dosing is likely determined by clinical judgment within the trial's parameters. The treatment period is set for a maximum of two days. Salbutamol sulfate is classified under the ATC code R03AC02, which identifies it as a selective β2-adrenoceptor agonist used in the treatment of obstructive airway diseases. The trial aims to evaluate the frequency of persistent pulmonary hypertension in newborns treated with this medication.

In addition to the experimental treatment, the trial utilizes **sodium chloride** as a non-experimental treatment. Sodium chloride is provided in the form of a solvent for parenteral use, specifically as Natrium chloratum 0.9% Kabi, with a concentration of 9 mg/ml. This solution is also administered via inhalation. The sodium chloride solution serves as a comparator or placebo in the trial, ensuring that the effects of the experimental medication can be accurately assessed. The ATC classification for sodium chloride is V07AB, which includes solvents and diluting agents, including irrigating solutions. The administration of sodium chloride follows the same dosing schedule as salbutamol sulfate, with a maximum treatment period of two days.

Efficacy in this clinical trial will be assessed through both primary and secondary endpoints. The primary endpoint is the assessment of the incidence of **Persistent Pulmonary Hypertension of the Newborn (PPHN)**, defined by the need for ventilation with an additional oxygen fraction in the respiratory mixture (FiO2) greater than 0.30, echocardiographic features of elevated pulmonary pressure, or a difference in pre- and post-ductal saturation greater than 10%. Secondary endpoints include scoring on the TTN score, prevalence of failures defined as the need for intubation, duration of respiratory support, hospitalization time, results of the acid-base balance (ABS) and ionogram, and the occurrence of adverse events.

These efficacy parameters will be measured and collected at various timepoints throughout the trial. The trial will utilize validated scales and laboratory tests to ensure accurate and reliable data collection. The trial is designed to evaluate the treatment effects of **salbutamol sulfate** in newborns born between 32 and 42 weeks of pregnancy. The trial is expected to conclude by December 31, 2025, with recruitment having started on September 1, 2021.