Nebulized Magnesium Sulfate and Sildenafil for Persistent Pulmonary Hypertension of Newborn

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Effectiveness of Nebulized Magnesium Sulfate Combined With Sildenafil Citrate in Persistent Pulmonary Hypertension of Newborn

Conditions
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Persistent Pulmonary Hypertension of Newborn

Intervention / Treatment
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* Drug: Magnesium sulfate
* Drug: Sildenafil Citrate
* Other: Isotonic saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Hours
Maximum Age: 72 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two groups of neonates with PPHN on mechanical ventilation: (1) NebMag group: receive nebulized magnesium sulfate and oral sildenafil citrate; (2) Control group: receive nebulized placebo (isotonic saline) and oral sildenafil citrate.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NebMag<br>Nebulized magnesium sulfate and oral sildenafil | Drug: Magnesium sulfate<br>* Nebulized magnesium sulfate (4 ml of 6.4% solution) every 15 minutes<br>* Other names: MgSO4;Drug: Sildenafil Citrate<br>* Oral sildenafil citrate at an initial dose of 1 mg/kg, with incremental increases by 0.5 mg/kg every 6 hours till reaching a target dose of 2mg/kg every 6 hours.<br>* Other names: Viagra;|
| Placebo Comparator: Control<br>Nebulized placebo (isotonic saline) and oral sildenafil | Drug: Sildenafil Citrate<br>* Oral sildenafil citrate at an initial dose of 1 mg/kg, with incremental increases by 0.5 mg/kg every 6 hours till reaching a target dose of 2mg/kg every 6 hours.<br>* Other names: Viagra;Other: Isotonic saline<br>* Nebulized isotonic saline (4 ml) every 15 minutes<br>* Other names: 0.9% NaCl;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Oxygenation index (OI) | OI will be calculated using the following formula: OI = [(FiO2 × MAP) / PaO2] (FiO2, fraction of inspired oxygen expressed in %; MAP, mean airway pressure in cmH2O/mmHg; and PaO2, partial pressure of arterial oxygen in mmHg). | From baseline to 2, 6, 12, and 24 hours following study drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean arterial blood pressure (MABP) |  | From baseline to 2, 6, 12, and 24 hours following study drug administration. | 
| Change in Vasoactive Inotropic Score (VIS) | The VIS will be calculated using the following formula: VIS = dopamine dose (µg/kg/min) + dobutamine dose (µg/kg/min) + 100 × epinephrine dose (µg/kg/min) + 100 × norepinephrine dose (µg/kg/min) + 10 × milrinone dose (µg/kg/min) + 10,000 × vasopressin dose (U/kg/min). | From baseline to 2, 6, 12, and 24 hours following study drug administration. | 
| Change in Pulmonary artery systolic pressure (PASP) | PASP will be estimated by echocardiography using the modified Bernoulli equation: PASP = (TRJV2 × 4) + RAP (TRJV, tricuspid regurgitation jet velocity; RAP, right atrial pressure). | From baseline to 24 hours after study drug administration | 
| Change in Serum magnesium level |  | From baseline to 24 hours after study drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neonate, persistent fetal circulation, persistent pulmonary hypertension of the newborn, PPHN, Magnesium Sulfate, Nebulizer, hypoxia, mechanical ventilation