The aim of this study is to evaluate the effectiveness of nebulized magnesium sulfate combined with sildenafil citrate, compared with sildenafil citrate alone, in treating neonates with severe persistent pulmonary hypertension on mechanical ventilation.

Persistent pulmonary hypertension of newborn (PPHN) is a serious condition that results from failure of the normal postnatal circulatory transition and is associated with significant mortality and morbidity. Advanced medical treatment, such as inhaled nitric oxide (iNO), high-frequency ventilation (HFV), and extracorporeal membrane oxygenation (ECMO) are commonly not available in developing countries. Intravenous magnesium sulfate has been shown to alleviate pulmonary hypertension but is associated with systemic hypotension and is less effective compared with iNO and sildenafil. Nebulized magnesium sulfate has been reported to be more effective and safer compared with intravenous magnesium sulfate in treating neonates with PPHN on mechanical ventilation. Combined nebulized magnesium and sildenafil has been studied in a small trial on spontaneously breathing neonates with PPHN but not on those connected to mechanical ventilation.

The aim of this study is to evaluate the effectiveness of nebulized magnesium sulfate combined with sildenafil citrate, compared with sildenafil citrate alone, in treating neonates with severe PPHN on mechanical ventilation. We hypothesize that neonates with severe PPHN connected to mechanical ventilation could benefit from taking continuous nebulization of magnesium sulfate combined besides sildenafil.

Inclusion Criteria:

• Gestational age ≥ 36 weeks
• Birth weight between 2.5 and 4 kg.
• Post-natal age between 6 and 72 hours.
• PPHN confirmed by echocardiography
• Oxygenation index (OI) > 30 on two occasions at least 15 minutes apart
• Connected to Mechanical Ventilation

Exclusion Criteria:

• Failure to obtain informed consent
• Newborns to mothers who received magnesium sulfate within 48 hours before labor.
• Congenital heart diseases, other than patent ductus arteriosus and foramen ovale.
• Major congenital anomalies (including congenital diaphragmatic hernia and lung hypoplasia).
• Prior need for cardiopulmonary resuscitation.
• Mean arterial blood pressure (MABP) < 35 mmHg despite therapy with volume infusions and vasoactive inotropes.
• Impaired kidney function.
• Prior administration of pulmonary vasodilators.
• Gastrointestinal intolerance or bleeding

Unidentified individual participant data will be available from the principal investigator upon reasonable request

Three years after publication of the study results

Unidentified individual participant data can be requested from the principal investigator

Each neonate will be assigned a unique identification number. Pharmacy will fill the active and placebo preparations in similar containers with sealed code for identification. Participants' families, treating clinicians, nurses, echocardiographers, and data collectors will be unaware of group assignment and drug/placebo therapy.