Clinical trial NCT04898114: Nebulized Magnesium Sulfate and Sildenafil for Persistent Pulmonary Hypertension of Newborn
Official title: Effectiveness of Nebulized Magnesium Sulfate Combined With Sildenafil Citrate in Persistent Pulmonary Hypertension of Newborn
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Persistent Pulmonary Hypertension of Newborn
Keywords: neonate
persistent fetal circulation
persistent pulmonary hypertension of the newborn
PPHN
Magnesium Sulfate
Nebulizer
hypoxia
mechanical ventilation
Lead sponsor: Sohag University
Sponsor class: OTHER
First posted: 2021-05-24
Enrollment: 40
Sex: ALL
Minimum age (years): 6
Maximum age (years): 72
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Oxygenation index (OI)
timeFrame: From baseline to 2, 6, 12, and 24 hours following study drug administration
Secondary outcomes:
measure: Change in Mean arterial blood pressure (MABP)
timeFrame: From baseline to 2, 6, 12, and 24 hours following study drug administration.
measure: Change in Vasoactive Inotropic Score (VIS)
timeFrame: From baseline to 2, 6, 12, and 24 hours following study drug administration.
measure: Change in Pulmonary artery systolic pressure (PASP)
timeFrame: From baseline to 24 hours after study drug administration
measure: Change in Serum magnesium level
timeFrame: From baseline to 24 hours after study drug administration
Other outcomes:
Locations:
city: Sohag
country: Egypt
facility: Neonatal Intensive Care Unit, Sohag University Hospital
Study officials:
affiliation: Sohag University
name: Elsayed Abdelkreem, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Abdelkreem E, Mahmoud SM, Aboelez MO, Abd El Aal M. Nebulized Magnesium Sulfate for Treatment of Persistent Pulmonary Hypertension of Newborn: A Pilot Randomized Controlled Trial. Indian J Pediatr. 2021 Aug;88(8):771-777. doi: 10.1007/s12098-020-03643-y. Epub 2021 Jan 8.
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citation: Nakwan N. The Practical Challenges of Diagnosis and Treatment Options in Persistent Pulmonary Hypertension of the Newborn: A Developing Country's Perspective. Am J Perinatol. 2018 Dec;35(14):1366-1375. doi: 10.1055/s-0038-1660462. Epub 2018 Jun 19.
citation: He Z, Zhu S, Zhou K, Jin Y, He L, Xu W, Lao C, Liu G, Han S. Sildenafil for pulmonary hypertension in neonates: An updated systematic review and meta-analysis. Pediatr Pulmonol. 2021 Aug;56(8):2399-2412. doi: 10.1002/ppul.25444. Epub 2021 May 13.
citation: Ho JJ, Rasa G. Magnesium sulfate for persistent pulmonary hypertension of the newborn. Cochrane Database Syst Rev. 2007 Jul 18;2007(3):CD005588. doi: 10.1002/14651858.CD005588.pub2.