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About
The purpose of this study is to determine whether intravenous sildenafil reduces pulmonary artery pressure and improves oxygenation in near-term and term infants with persistent pulmonary hypertension.
Full description
Term infants with respiratory failure and persistent pulmonary hypertension (PPHN) are among the most critically ill infants in the NICU, with significant mortality and morbidity reported even for infants with moderate disease. Currently, management is largely supportive, and includes oxygen, mechanical ventilation (conventional or high frequency ventilation), and exogenous surfactant therapy. Inhaled nitric oxide (iNO) is a pulmonary vasodilator that was approved for the treatment of hypoxic respiratory failure (HRF) and PPHN of the newborn in 1999 based on clinical trials showing a reduction in the need for rescue treatment with extracorporeal membrane oxygenation (ECMO).
One promising therapy to decrease pulmonary arterial pressure and improve oxygenation is sildenafil. Sildenafil is a cGMP-specific phosphodiesterase inhibitor that causes relatively selective pulmonary vasodilation. The use of intravenous (IV) sildenafil was recently FDA approved for use in adults in PPHN. A pilot trial studying dose response and pharmacokinetics in 36 term newborns with PPHN found that IV sildenafil was well tolerated and has the potential to induce marked improvements in oxygenation. The data from this pilot trial provided background to support the dosing regimen for this Phase II trial. We hypothesize that IV sildenafil will acutely reduce pulmonary artery pressure and improve oxygenation in near-term and term infants with PPHN, thus reducing the need for rescue therapy iNO and/or ECMO.
Enrollment
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Inclusion criteria
Signed informed consent from legally acceptable guardian
PPHN or hypoxemic respiratory failure associated with:
Greater than or equal to 35 weeks gestation
Age at enrollment less than 72 hours
Moderate hypoxemic respiratory failure, with 12<OI<35 (oxygenation index, calculated as FiO2 * mean airway pressure * 100 / postductal PaO2)
Absence of structural heart disease (except patent ductus arteriosus, atrial septal defect <1cm, or muscular ventricular septal defect < 2mm)
Absence of lethal congenital anomaly
Not participating in another concurrent experimental study
Exclusion criteria
Prior or immediate need for iNO or ECMO
Profound hypoxemia: qualifying PaO2 <30 mmHg, from a blood gas drawn within 30 minutes of starting study drug infusion.
Hypotension: Mean arterial pressure <35 mmHg
Congenital heart disease, except patent ductus arteriosus, atrial septal defect <1cm, or muscular ventricular septal defect <2mm
Congenital diaphragmatic hernia or lung hypoplasia syndromes, diagnosed on the basis of prolonged oligohydramnios
Active seizures
Apgar score of <3 at 5 minutes
Bleeding diathesis
Receipt of any other experimental drug or device
Receipt of any prohibited concurrent medication:
Known hereditary degenerative retinal disorders such as retinitis pigmentosa.
In the opinion of the investigator, a subject who is not likely to complete the study or would be considered inappropriate for the study, for any reason.
Primary purpose
Allocation
Interventional model
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3 participants in 2 patient groups, including a placebo group
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Data sourced from clinicaltrials.gov
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