Oral Sildenafil in Persistent Pulmonary Hypertension Secondary to Meconium Aspiration Syndrome in Newborns

Study Overview
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Brief Summary
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The purpose of this study is to to study the role of oral Sildenafil in Persistent Pulmonary Hypertension of Newborn (PPHN) secondary to Meconium Aspiration Syndrome (MAS) in newborns and to study risk factors of MAS developing into PPHN.

Detailed Description
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Design: Randomized control trial Setting: Neonatal intensive care unit in a tertiary care hospital Patients: Patients diagnosed with MAS with PPHN according to clinical criteria. 97 patients with MAS were enrolled in the study over a period of 8 months, out of which 40 patients with PPHN were randomized into two groups. Intervention: Group A received Sildenafil through a feeding tube (1 mg/kg/dose q6h) for 8 doses. Group B received a placebo. Outcome measures: Improvement in oxygen saturation (SpO2), oxygenation index (OI), duration of hospitalization and mechanical ventilation and mortality.

Official Title
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Oral Sildenafil in Persistent Pulmonary Hypertension of Neonates Secondary to Meconium Aspiration Syndrome: A Randomized Placebo Controlled Trial

Conditions
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Meconium Aspiration Syndrome, Persistent Pulmonary Hypertension of Newborn

Intervention / Treatment
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* Drug: Oral Sildenafil
* Drug: Placebo (distilled water)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newborns were diagnosed with MAS if any of the two of the following three criteria were present. (1) Meconium staining of liquor or staining of umbilical cord or skin or nails. (2) Respiratory distress, within one hour of birth. (3) Radiological evidence of aspiration pneumonitis (atelectasis and/or hyperinflation). Newborns with MAS diagnosed with clinical PPHN were enrolled in the study for drug trial. PPHN was determined either clinically by loud P2(second component of second heart sound), 10% or greater pre-/post ductal difference in arterial oxygenation (obtained by acid base gas analysis) or upper limb- lower limb SpO2 difference (obtained by pulse oximetry). Exclusion Criteria: (a) babies with congenital heart disease (b) congenital anomalies particularly those which were incompatible to life or which was the cause for respiratory distress e.g. diaphragmatic hernia (c) Respiratory morbidities such as hyaline membrane disease, congenital pneumonia (d) Babies with PPHN secondary to MAS admitted after 12 hours of delivery (e) Non availability of consent of guardian for interventional procedures

Ages Eligible for Study
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Minimum Age: 1 Minute
Maximum Age: 12 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Oral Sildenafil<br>In group A, newborns received oral Sildenafil solution through feeding tube which was prepared by crushing a 50 mg tablet of sildenafil in distilled water to make a concentration of 5 mg/ml. The protocol for dosing was (1) first dose of 1 mg/kg/dose within 30 minutes admission or within 12 hours of delivery (whichever earlier), (2) Dosing every six hours for a maximum of 8 doses. | Drug: Oral Sildenafil<br>* Patients were randomized into two groups. Placebo was prepared with distilled water. In group A, newborns received oral Sildenafil solution through feeding tube which was prepared by crushing a 50 mg tablet of sildenafil in distilled water to make a concentration of 5 mg/ml. In group B, newborns received placebo. The protocol for dosing was (1) first dose of 1 mg/kg/dose within 30 minutes admission or within 12 hours of delivery (whichever earlier), (2) Dosing every six hours for a maximum of 8 doses, (3) Dose was doubled if the oxygenation index (OI) or SpO2 did not improve (If OI continued to be <10% of previous value and SpO2 was not increasing >5 of previous value) and blood pressure remained stable<br>* Other names: Integra;|
| Placebo Comparator: Distilled water<br>In group B, newborns received placebo. The protocol for dosing was (1) first dose of 1 mg/kg/dose within 30 minutes admission or within 12 hours of delivery (whichever earlier), (2) Dosing every six hours for a maximum of 8 doses. | Drug: Placebo (distilled water)<br>* Distill water oral<br>* Other names: Water;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in oxygen saturation (SpO2) | Preductal and postductal oxygen saturation (SpO2) 2 hours after dose of oral sildenafil (24 hours and 48 hours) | 26 hours, 50 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxygenation index | Oxygenation index of neonates kept on ventilator 2 hours after dose of oral sildenafil (24 hours and 48 hours) [Oxygenation index (OI) = Mean airway pressure (cm H2O) × FiO2 × 100/ PaO2 [fraction of inspired oxygen- FiO2] [Arterial partial pressure of oxygen- PaO2] | 26 hours, 50 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MAS, PPHN, Sildenafil, Newborn, Pulmonary Hypertension