Study of Sildenafil to Treat Newborns With Persistent Pulmonary Hypertension
Condition: Persistent Pulmonary Hypertension; Respiratory Failure
MeSH terms: Hypertension, Pulmonary; Respiratory Insufficiency; Hypertension
Intervention: Intravenous Sildenafil; Placebo
Intervention description: 0.4 mg/kg bolus, followed by a continuous infusion of 1.6 mg/kg/day or an equivalent volume of placebo (D5W); infusion will be initiated as a bolus over 3 hours, followed by a controlled continuous infusion for up to 7 days.; An equivalent volume of placebo (D5W)infusion will be initiated as a bolus over 3 hours, followed by a controlled continuous infusion for up to 7 days.
Intervention MeSH terms: Sildenafil Citrate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 3.0
Sex: All
Maximum age: 72 Hours
Healthy volunteers: No
Keywords: newborns; respiratory failure; pulmonary hypertension; treatment

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed informed consent from legally acceptable guardian

          -  PPHN or hypoxemic respiratory failure associated with:

               -  Idiopathic PPHN

               -  Meconium aspiration syndrome

               -  Respiratory distress syndrome

               -  Sepsis

               -  Pneumonia

          -  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:

               -  Potent cytochrome P450 3A4 inhibitors (e.g., erythromycin, ketoconazole,
                  itraconazole and protease inhibitors)

               -  Endothelin antagonists (e.g. Tracleer/bosentan)

               -  Intravenous nitrates or nitric oxide donors

          -  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.