Clinical Trial: Chronic Sildenafil for Severe Diaphragmatic Hernia

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Chronic Sildenafil for Severe Diaphragmatic Hernia

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 Summary: 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.
Sponsor: University of California, San Francisco

Current Primary Outcome: Estimated systolic pulmonary arterial pressure at final echocardiogram [ Time Frame: 7 weeks ]

Original Primary Outcome: Pulmonary vascular resistance at final cardiac catheterization (7 weeks from initial cardiac catheterization)

Current Secondary Outcome:

  • Systemic levels of vasoactive substances at the time of final echocardiogram [ Time Frame: 7 weeks ]
  • Adverse effects of sildenafil therapy [ Time Frame: 2 years ]
  • Somatic growth at 1 and 2 years of age [ Time Frame: 2 years ]
  • Neurodevelopmental outcome at 1 and 2 years of age [ Time Frame: 2 years ]
  • Respiratory status at 1 and 2 years of age [ Time Frame: 2 years ]


Original Secondary Outcome:

  • Pulmonary arterial pressure at final cardiac catheterization (7 weeks)
  • Pulmonary metabolism of vasoactive substances at final cardiac catheterization (7 weeks)
  • Adverse effects of sildenafil therapy
  • Somatic growth at 1 and 2 years of age
  • Neurodevelopmental outcome at 1 and 2 years of age
  • Respiratory status at 1 and 2 years of age


Information By: University of California, San Francisco

Dates:
Date Received: August 22, 2005
Date Started: February 2006
Date Completion:
Last Updated: August 11, 2014
Last Verified: August 2014