Treatment of Persistent Pulmonary Hypertension in Neonates With Nebulized Magnesium Sulfate

NCT06603766 | Completed Phase 2 Results

• 1 other identifier: 39-9-204
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

we conducted this study to compare between effect of nebulized and intravenous magnesium sulfate (MgSO₄) for better treatment of persistent pulmonary hypertension of neonates with less side effects.

Conditions

Magnesium Sulfate - PPHN

Keywords

PPHN; magnesium sulfate; Neonates

Outcome Measures

Primary Outcomes (4)

• Mean Airway Pressure (cm H2O)

  from baseline to 12 and 24 hours after administering the study drug

• Fraction of Inspired Oxygen (FiO2) (%)

  from baseline to 12 and 24 hours after administering the study drug

• PaO2 (mmHg)

  kPa x 7.5 converts to the equivalent PaO2 in mmHg

  from baseline to 6, 12 and 24 hours after administering the study drug

• Tracking Changes in the Oxygenation Index (OI)

  OI evaluates both oxygenation and ventilatory support, aiding decisions on Extracorporeal Membrane Oxygenation (ECMO) necessity in newborns with PPHN. OI calculated as (Mean Airway Pressure (cm H2O) x Fraction of Inspired Oxygen (%) x 100) ÷ (PaO2 (kPa) x 7.5). OI is routinely used as an indicator of severity of hypoxemic respiratory failure (HRF) in neonates, with an arbitrary cutoff of 15 or less for mild HRF, between 16 and 25 for moderate HRF, between 26 and 40 for severe HRF, and more than 40 for very severe HRF

  from baseline to 12 and 24 hours after administering the study drug

Secondary Outcomes (2)

• the Variations in Mean Arterial Blood Pressure (MABP)

  at 0, 12, and 24 hours post administration of the study drug relative to baseline

• the Alterations in Serum Magnesium Levels (mmol/L)

  from baseline to 12 hours following the administration of the study drug.

Study Arms (2)

Nebulized magnesium (NebMag) group 1

ACTIVE COMPARATOR

NebMag group (n=20) was administered nebulized isotonic magnesium (64 mg/mL). For nebulization, an isotonic MgSO₄ solution (64 mg/mL) was formulated by diluting a 10% intravenous preparation of MgSO₄ heptahydrate with sterile distilled water. 4 mL aliquots of the isotonic MgSO₄ solution (containing 256 mg of MgSO₄) were administered every 15 minutes through the jet nebulizer connected to the ventilator during the 24 hour study period.

Drug: Inhalational magnesium sulfate

Intravenous magnesium (IVMag) group 2

ACTIVE COMPARATOR

IVMag group (n=20) received intravenous magnesium. For intravenous administration, a 10% MgSO₄ solution was prepared by diluting a 50% intravenous formulation of MgSO₄ heptahydrate with 5% glucose and administrated in a loading dose of 2 mL/kg over 30 minutes (equivalent to 200 mg/kg of MgSO₄), followed by a continuous infusion at a rate of 0.5 mL/kg/h (equivalent to 50 mg/kg/h of MgSO₄) over the 24 hour study period.

Drug: IV Magnesium Sulfate

Interventions

IV Magnesium Sulfate DRUG

MgSO₄'s mechanism in PPHN includes activating cellular processes, modulating membrane excitability, and acting as a physiological calcium antagonist. It exerts sedative, muscle relaxant, and bronchodilatory properties, while concurrently inducing a state of alkalosis.

Also known as: IV MgSO4

Intravenous magnesium (IVMag) group 2

Inhalational magnesium sulfate DRUG

It gives us the same mechanism of action as IV MgSO4 with less side effects.

Also known as: Inhalational MgSO4

Nebulized magnesium (NebMag) group 1

Eligibility Criteria

• Age: 1 Hour - 3 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Newborns with documented persistent pulmonary hypertension as confirmed by echocardiography.
• Neonates born at ≥ 35 wk. gestation with a birth weight of 2.5-4 kg
• Neonates have to be connected to mechanical ventilation with an oxygenation index (OI) \>30 on two occasions at least 15 min apart.
• The echocardiogram had to show a predominant right-to-left or bidirectional shunt (through ductus arteriosus and/or foramen oval) and/or tricuspid regurgitant jet with a pressure gradient ≥ 2/3 of the systemic systolic blood pressure.

You may not qualify if:

• Infants of parents who refuse to give informed consent.
• Infants of mothers who receive magnesium sulfate within 48 h before labor.
• Congenital heart diseases other than patent ductus arteriosus (PDA) 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; and prior administration of pulmonary vasodilators or prior administration of surfactant.

Sponsors & Collaborators

• Benha University: lead

Study Sites (1)

Pediatrics Department, Faculty of Medicine, Benha University.

Benha, Egypt., Egypt

Location

MeSH Terms

Interventions

Magnesium Sulfate

Intervention Hierarchy (Ancestors)

Magnesium Compounds; Inorganic Chemicals; Sulfates; Sulfuric Acids; Sulfur Acids; Sulfur Compounds

Limitations and Caveats

First, the study involved a limited group of neonates with PPHN. Second, a single dosage of magnesium was administered via continuous nebulization in this trial. It is still technically difficult to have a reliable \& effective nebulization system while using mechanical breathing. Thirdly, effects of nebulized magnesium sulfate in combination with other pulmonary vasodilators were not disclosed by study. Finally, because of study's constrained time frame, critical outcomes could not be addressed.

Results Point of Contact

• Title: Dr. Heba Morsy Saad El Din El Ganady
• Organization: faculty of medicine Benha University

Heba.Aljanadi21@fmed.bu.edu.eg

+201111211367

Study Officials

• Osama Z. El Feky, Professor

  Pediatrics Department, Faculty of Medicine, Benha University, Benha, Egypt.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: September 16, 2024
• First Posted: September 19, 2024
• Study Start: October 1, 2021
• Primary Completion: September 28, 2023
• Study Completion: September 28, 2023
• Last Updated: February 5, 2025
• Results First Posted: February 5, 2025

Record last verified: 2025-02

Locations

EG (1)