Nebulized Magnesium Sulfate and Sildenafil for Persistent Pulmonary Hypertension of Newborn

Persistent Pulmonary Hypertension of Newborn Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04898114
• Other study ID #: Neb-Mag-2
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 2, 2021
• Est. completion date: September 1, 2023

Study information

• Verified date: July 2023
• Source: Sohag University
• Contact: Elsayed Abdelkreem, MD, PhD
• Phone: 00201114232126
• Email: d.elsayedmohammed[@]med.sohag.edu.eg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: September 1, 2023
• Est. primary completion date: August 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Hours to 72 Hours

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Persistent Fetal Circulation Syndrome
• Persistent Pulmonary Hypertension of Newborn

Intervention

Drug:
• Magnesium sulfate
Nebulized magnesium sulfate (4 ml of 6.4% solution) every 15 minutes
• 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.

Other:
• Isotonic saline
Nebulized isotonic saline (4 ml) every 15 minutes

Locations

Country	Name	City	State
Egypt	Neonatal Intensive Care Unit, Sohag University Hospital	Sohag

Sponsors (1)

Lead Sponsor	Collaborator
Sohag University

Country where clinical trial is conducted

Egypt, 

References & Publications (7)

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. — View Citation

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/s40748-018-0093-1. eCollection 2018. — View 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. — View 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. — View Citation

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. — View Citation

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in Mean arterial blood pressure (MABP)		From baseline to 2, 6, 12, and 24 hours following study drug administration.
Secondary	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.
Secondary	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
Secondary	Change in Serum magnesium level		From baseline to 24 hours after study drug administration