Nebulized Magnesium Sulfate and Sildenafil for Persistent Pulmonary Hypertension of Newborn

Phase 1

Recruiting

• Conditions: Persistent Pulmonary Hypertension of Newborn
• Interventions: Drug: Magnesium sulfate; Other: Isotonic saline; Drug: Sildenafil Citrate

• Registration Number: NCT04898114
• Lead Sponsor: Sohag University

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2021-05-20
• Study First Submitted QC: 2021-05-21
• Study First Posted: 2021-05-24
• Study Start: 2021-06-02
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-26
• Last Update Posted: 2024-11-27
• Primary Completion: 2025-04-30
• Study Completion: 2025-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	Isotonic saline	Nebulized placebo (isotonic saline) and oral sildenafil
NebMag	Magnesium sulfate	Nebulized magnesium sulfate and oral sildenafil
NebMag	Sildenafil Citrate	Nebulized magnesium sulfate and oral sildenafil
Control	Sildenafil Citrate	Nebulized placebo (isotonic saline) and oral sildenafil

Primary Outcome Measures

Name	Time	Method
Change in Oxygenation index (OI)	From baseline to 2, 6, 12, and 24 hours following study drug administration	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).

Secondary Outcome Measures

Name	Time	Method
Change in Pulmonary artery systolic pressure (PASP)	From baseline to 24 hours after study drug administration	PASP will be estimated by echocardiography using the modified Bernoulli equation: PASP = (TRJV2 × 4) + RAP (TRJV, tricuspid regurgitation jet velocity; RAP, right atrial pressure).
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)	From baseline to 2, 6, 12, and 24 hours following study drug administration.	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).
Change in Serum magnesium level	From baseline to 24 hours after study drug administration

Trial Locations

Locations (1)

Neonatal Intensive Care Unit, Sohag University Hospital; 🇪🇬 Sohag, Egypt