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

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

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.

Study Overview

• Status: Completed
• Conditions: Meconium Aspiration Syndrome; Persistent Pulmonary Hypertension of Newborn
• Intervention / Treatment: Drug: Oral Sildenafil; Drug: Placebo (distilled water)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 4

Contacts and Locations

Study Locations

• India
  • Gujarat
    • Bhavnagar, Gujarat, India, 364002
      • NICU, Pediatrics department, SirTakhtasinhjiGH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 minute to 12 hours (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oral Sildenafil; 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; 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; Other Names: Viagra; Integra
Placebo Comparator: Distilled water; 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); Distill water oral; Other Names: Water

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality of patients enrolled in study	During time of hospital stay(upto 4 weeks).	Upto 4 weeks

Collaborators and Investigators

• Sponsor: Sir Takhtasinhji General Hospital

Publications and helpful links

General Publications

• Vargas-Origel A, Gomez-Rodriguez G, Aldana-Valenzuela C, Vela-Huerta MM, Alarcon-Santos SB, Amador-Licona N. The use of sildenafil in persistent pulmonary hypertension of the newborn. Am J Perinatol. 2010 Mar;27(3):225-30. doi: 10.1055/s-0029-1239496. Epub 2009 Oct 28.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: December 18, 2012
• First Submitted That Met QC Criteria: December 21, 2012
• First Posted (Estimate): December 31, 2012

Study Record Updates

• Last Update Posted (Actual): May 20, 2022
• Last Update Submitted That Met QC Criteria: May 15, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Pulmonary Hypertension; PPHN; Newborn; Sildenafil; MAS
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Fetal Diseases; Pregnancy Complications; Lung Injury; Hypertension; Syndrome; Hypertension, Pulmonary; Persistent Fetal Circulation Syndrome; Meconium Aspiration Syndrome; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate
• Other Study ID Numbers: Sildenafil

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Available for six months on request
• IPD Sharing Time Frame: six months
• IPD Sharing Access Criteria: on demand
• IPD Sharing Supporting Information Type: Clinical Study Report (CSR)