Nebulized Magnesium Sulfate and Sildenafil for Persistent Pulmonary Hypertension of Newborn

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Magnesium sulfate
  Nebulized magnesium sulfate (4 ml of 6.4% solution) every 15 minutes
• Препарат Sildenafil Citrate
  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.
• Другое Isotonic saline
  Nebulized isotonic saline (4 ml) every 15 minutes

Первичные конечные точки

• Change in Oxygenation index (OI) [Срок оценки: From baseline to 2, 6, 12, and 24 hours following study drug administration]

Вторичные конечные точки (4)

• Change in Mean arterial blood pressure (MABP) [Срок оценки: From baseline to 2, 6, 12, and 24 hours following study drug administration.]
• Change in Vasoactive Inotropic Score (VIS) [Срок оценки: From baseline to 2, 6, 12, and 24 hours following study drug administration.]
• Change in Pulmonary artery systolic pressure (PASP) [Срок оценки: From baseline to 24 hours after study drug administration]
• Change in Serum magnesium level [Срок оценки: From baseline to 24 hours after study drug administration]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Египет · 1 центр

• Neonatal Intensive Care Unit, Sohag University Hospital — Sohag

Публикации

• 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. PMID 33415555
• Mandell E, Kinsella JP, Abman SH. Persistent pulmonary hypertension of the newborn. Pediatr Pulmonol. 2021 Mar;56(3):661-669. doi: 10.1002/ppul.25073. PMID 32930508
• El-Khuffash A, McNamara PJ, Breatnach C, Bussmann N, Smith A, Feeney O, Tully E, Griffin J, de Boode WP, Cleary B, Franklin O, Dempsey E. The use of milrinone in neonates with persistent pulmonary hypertension of the newborn - a randomised controlled trial pilot study (MINT 1): study protocol and review of literature. Matern Health Neonatol Perinatol. 2018 Dec 3;4:24. doi: 10.1186/s40748-018-0093- PMID 30524749
• Lai MY, Chu SM, Lakshminrusimha S, Lin HC. Beyond the inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Pediatr Neonatol. 2018 Feb;59(1):15-23. doi: 10.1016/j.pedneo.2016.09.011. Epub 2017 Aug 10. PMID 28923474
• 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. PMID 29920641
• 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. PMID 33983650
• 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. PMID 17636807

Идентификаторы

NCT: NCT04898114 · Neb-Mag-2

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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