A Trial of Phosphodiesterase-5 Inhibitor in Neonatal Congenital Diaphragmatic Hernia (TOP-CDH)
Status:
Not yet recruiting
Trial end date:
2023-09-01
Target enrollment:
Participant gender:
Summary
Congenital diaphragmatic hernia (CDH) occurs in approximately 1 in 3000 US live births,
similar to the incidence seen within the Utah Birth Defects cohort. The diaphragmatic defect
compromises lung growth and alters pulmonary vascular development. This is reflected
postnatally as respiratory failure, pulmonary hypertension (PH) and overall cardiopulmonary
dysfunction, particularly post-repair. Currently, optimal management of post-repair PH
remains poorly investigated. Sildenafil citrate is a highly selective phosphodiesterase-5
inhibitor that increases cGMP levels, leading to smooth muscle relaxation and an
anti-proliferative effect within the pulmonary vasculature. It is used off-label for many
neonatal PH disorders, including PH associated with bronchopulmonary dysplasia and idiopathic
persistent PH. Most neonates with CDH born within the Mountain West referral basin are
managed at our quaternary care center, Primary Children's Hospital (PCH). Of these neonates
with PH, approximately 25% have been treated with off-label sildenafil. However, neither our
group nor others have developed/published a standardized approach for either initiating or
discontinuing sildenafil therapy in this group of patients. Thus, we aim to assess the safety
and effectiveness of sildenafil therapy for PH in neonates with CDH within the Utah cohort.
Given the relatively short-term outcome and small sample size for this trial we plan to use
our data to support a larger multicenter randomized trial targeting long-term cardiopulmonary
outcomes of infants with CDH and post-repair PH.