Nebulized Magnesium Sulfate and Sildenafil for Persistent Pulmonary Hypertension of Newborn

NCT04898114 | Recruiting Phase 1

• 1 other identifier: Neb-Mag-2
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Persistent Pulmonary Hypertension of Newborn

Keywords

neonate; persistent fetal circulation; persistent pulmonary hypertension of the newborn; PPHN; Magnesium Sulfate; Nebulizer; hypoxia; mechanical ventilation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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.

• Change in Pulmonary artery systolic pressure (PASP)

  From baseline to 24 hours after study drug administration

• Change in Serum magnesium level

  From baseline to 24 hours after study drug administration

Study Arms (2)

NebMag

EXPERIMENTAL

Nebulized magnesium sulfate and oral sildenafil

Drug: Magnesium sulfate; Drug: Sildenafil Citrate

Control

PLACEBO COMPARATOR

Nebulized placebo (isotonic saline) and oral sildenafil

Drug: Sildenafil Citrate; Other: Isotonic saline

Interventions

Magnesium sulfate DRUG

Nebulized magnesium sulfate (4 ml of 6.4% solution) every 15 minutes

Also known as: MgSO4

NebMag

Sildenafil Citrate DRUG

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.

Also known as: Viagra

Control; NebMag

Isotonic saline OTHER

Nebulized isotonic saline (4 ml) every 15 minutes

Also known as: 0.9% NaCl

Control

Eligibility Criteria

• Age: 6 Hours - 72 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sohag University: lead

Study Sites (1)

Neonatal Intensive Care Unit, Sohag University Hospital

Sohag, 82524, Egypt

RECRUITING

Related 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.

  PMID: 33415555 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 30524749 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Persistent Fetal Circulation Syndrome; Hypoxia

Interventions

Magnesium Sulfate; Sildenafil Citrate; Sodium Chloride; Saline Solution

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Magnesium Compounds; Inorganic Chemicals; Sulfates; Sulfuric Acids; Sulfur Acids; Sulfur Compounds; Sulfonamides; Amides; Organic Chemicals; Sulfones; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Chlorides; Hydrochloric Acid; Chlorine Compounds; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Elsayed Abdelkreem, MD, PhD

  Sohag University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elsayed Abdelkreem, MD, PhD

CONTACT

00201114232126; d.elsayedmohammed@med.sohag.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Each neonate will be assigned a unique identification number. Pharmacy will fill the active and placebo preparations in similar containers with sealed code for identification. Participants' families, treating clinicians, nurses, echocardiographers, and data collectors will be unaware of group assignment and drug/placebo therapy.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer of Pediatrics

Model Details: 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.

Study Record Dates

• First Submitted: May 20, 2021
• First Posted: May 24, 2021
• Study Start: June 2, 2021
• Primary Completion: April 30, 2025
• Study Completion: June 1, 2025
• Last Updated: November 27, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Three years after publication of the study results
• Access Criteria: Unidentified individual participant data can be requested from the principal investigator

Locations

EG (1)