Oral Sildenafil in Persistent Pulmonary Hypertension Secondary to Meconium Aspiration Syndrome in Newborns - Full Text View

Purpose

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	Intervention	Phase
Meconium Aspiration Syndrome Persistent Pulmonary Hypertension of Newborn	Drug: Oral Sildenafil Drug: Placebo (distilled water)	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Subject) Primary Purpose: Treatment
Official Title:	Oral Sildenafil in Persistent Pulmonary Hypertension Secondary to Meconium Aspiration Syndrome in Newborns: A Randomized Placebo Controlled Trial

Resource links provided by NLM:

MedlinePlus related topics: Drinking Water High Blood Pressure Pulmonary Hypertension

Drug Information available for: Sildenafil Sildenafil citrate

U.S. FDA Resources

Further study details as provided by Sir Takhtasinhji General Hospital:

Primary Outcome Measures:

Improvement in oxygen saturation (SpO2) [ Time Frame: 26 hours, 50 hours ] [ Designated as safety issue: No ]
Preductal and postductal oxygen saturation (SpO2) 2 hours after dose of oral sildenafil (24 hours and 48 hours)

Secondary Outcome Measures:

Oxygenation index [ Time Frame: 26 hours, 50 hours ] [ Designated as safety issue: No ]
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:

Mortality of patients enrolled in study [ Time Frame: Upto 4 weeks ] [ Designated as safety issue: Yes ]
During time of hospital stay(upto 4 weeks).

Enrollment:	96
Study Start Date:	December 2011
Study Completion Date:	September 2012
Primary Completion Date:	August 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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)

Arms

Assigned Interventions

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)

Eligibility

Ages Eligible for Study:	up to 12 Hours
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01757782

Sponsors and Collaborators

Sir Takhtasinhji General Hospital

Investigators

Principal Investigator:

Jayendra R Gohil, MD

Professor of Pediatrics, Dept of 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, Professor in Pediatrics, Sir Takhtasinhji General Hospital
ClinicalTrials.gov Identifier:	NCT01757782 History of Changes
Other Study ID Numbers:	Sildenafil
Study First Received:	December 18, 2012
Last Updated:	December 21, 2012
Health Authority:	India: Institutional Review Board

Additional relevant MeSH terms:

Hypertension
Hypertension, Pulmonary
Meconium Aspiration Syndrome
Persistent Fetal Circulation Syndrome
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Lung Injury
Respiration Disorders
Fetal Diseases

Pregnancy Complications
Infant, Newborn, Diseases
Sildenafil
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 16, 2013