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

• ClinicalTrials.gov Identifier: NCT01757782
• Recruitment Status: Completed
• First Posted: December 31, 2012
• Last Update Posted: May 20, 2022
• Sponsor: Sir Takhtasinhji General Hospital
• Information provided by (Responsible Party): Jayendra R. Gohil, MD, PROF., Sir Takhtasinhji General Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Meconium Aspiration Syndrome; Persistent Pulmonary Hypertension of Newborn	Drug: Oral Sildenafil; Drug: Placebo (distilled water)	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 96 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Oral Sildenafil in Persistent Pulmonary Hypertension of Neonates Secondary to Meconium Aspiration Syndrome: A Randomized Placebo Controlled Trial
• Study Start Date: December 2011
• Actual Primary Completion Date: August 2012
• Actual Study Completion Date: September 2012

Arms and Interventions

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 Name: Water

Outcome Measures

Primary Outcome Measures :

1. Improvement in oxygen saturation (SpO2) [ Time Frame: 26 hours, 50 hours ]
   Preductal and postductal oxygen saturation (SpO2) 2 hours after dose of oral sildenafil (24 hours and 48 hours)

Secondary Outcome Measures :

1. Oxygenation index [ Time Frame: 26 hours, 50 hours ]
   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]

Other Outcome Measures:

1. Mortality of patients enrolled in study [ Time Frame: Upto 4 weeks ]
   During time of hospital stay(upto 4 weeks).

Eligibility Criteria

• Ages Eligible for Study: up to 12 Hours (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

India

NICU, Pediatrics department, SirTakhtasinhjiGH

Bhavnagar, Gujarat, India, 364002

Sponsors and Collaborators

Sir Takhtasinhji General Hospital

Investigators

• Principal Investigator: Jayendra R Gohil, MD; Professor Pediatrics, Govt Medical College, Bhavnagar, Gujarat, India

More Information

Publications:

Vargas-Origel A, Gómez-Rodríguez G, Aldana-Valenzuela C, Vela-Huerta MM, Alarcón-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.

• Responsible Party: Jayendra R. Gohil, MD, PROF., Professor in Pediatrics, Sir Takhtasinhji General Hospital
• ClinicalTrials.gov Identifier: NCT01757782
• Other Study ID Numbers: Sildenafil
• First Posted: December 31, 2012
• Last Update Posted: May 20, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Available for six months on request
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: six months
• Access Criteria: on demand

Keywords provided by Jayendra R. Gohil, MD, PROF., Sir Takhtasinhji General Hospital:

MAS; PPHN; Sildenafil; Newborn; Pulmonary Hypertension

Additional relevant MeSH terms:

Hypertension, Pulmonary; Meconium Aspiration Syndrome; Persistent Fetal Circulation Syndrome; Hypertension; Syndrome; Disease; Pathologic Processes; Vascular Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Lung Injury; Respiration Disorders; Fetal Diseases; Pregnancy Complications; Infant, Newborn, Diseases; Sildenafil Citrate; Vasodilator Agents; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Urological Agents