Conditions: Hernia, Diaphragmatic Hypertension, Pulmonary Hypoplasia, Pulmonary
Keywords: Chronic lung disease Nitric oxide cyclic guanosine monophosphate phosphodiesterase inhibitor
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 9
Healthy volunteers: no

Brief summary:
The purpose of this study is to test if sildenafil is effective in the treatment of infants with severe congenital diaphragmatic hernia (determined by the presence of prolonged pulmonary hypertension or prolonged oxygen supplementation on mechanical ventilation), as measured by the estimated pulmonary artery systolic pressure following treatment.

Detailed description:
Congenital diaphragmatic hernia (CDH) is a condition characterized by pulmonary parenchymal and vascular hypoplasia. Severe CDH carries a high rate of mortality, and significant morbidity among survivors. This proposal is a randomized, blinded, placebo-controlled study designed to evaluate the efficacy and potential mechanisms of activity of sildenafil, a phosphodiesterase-5 inhibitor, for treatment of severe CDH. Infants who meet criteria at ≥10d of age predicting a poor outcome \[death or chronic lung disease (CLD) severe enough to require hospital discharge on supplemental oxygen (O2)\] will be eligible for the study. Infants whose parents consent for the study will undergo an initial echocardiogram to assess the degree of pulmonary hypertension. They will then begin either sildenafil or placebo therapy for a 45d course. A final echocardiogram will be performed after the experimental drug course is completed. The pulmonary arterial systolic pressure estimate during hyperoxic conditions will be compared between the sildenafil and placebo groups. Infants from either group who have severely elevated pulmonary arterial pressure (despite supplemental O2) will be considered for open-label sildenafil, which will continue after hospital discharge, depending on the results of a cardiac catheterization performed for clinical care.

Arms:
arm 1: Sildenafil x 45 days arm 2: Placebo x 45 d

Interventions: intervention 1: sildenafil intervention 2: Placebo
Intervention descriptions: intervention 1: Sildenafil 0.5 mg/kg every 6 hours orally x 45 d intervention 2: Placebo suspension (equal volume to experimental drug) x 45 days

Protocol document: