Persistent Pulmonary Hypertension of Newborn
Conditions
Keywords
neonate, persistent fetal circulation, persistent pulmonary hypertension of the newborn, PPHN, Magnesium Sulfate, Nebulizer, hypoxia, mechanical ventilation
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.
Interventions
DRUGMagnesium sulfate
Nebulized magnesium sulfate (4 ml of 6.4% solution) every 15 minutes
DRUGSildenafil 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.
OTHERIsotonic saline
Nebulized isotonic saline (4 ml) every 15 minutes
Sponsors
Sohag University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
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.
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.
Eligibility
Sex/Gender
ALL
Age
6 Hours to 72 Hours
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Oxygenation index (OI) | From baseline to 2, 6, 12, and 24 hours following study drug administration | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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). |
| Change in Pulmonary artery systolic pressure (PASP) | From baseline to 24 hours after study drug administration | PASP will be estimated by echocardiography using the modified Bernoulli equation: PASP = (TRJV2 × 4) + RAP (TRJV, tricuspid regurgitation jet velocity; RAP, right atrial pressure). |
| Change in Serum magnesium level | From baseline to 24 hours after study drug administration | — |
Countries
Egypt
Contacts
Primary ContactElsayed Abdelkreem, MD, PhD
Outcome results
None listed