A Trial of Phosphodiesterase-5 Inhibitor in Neonatal Congenital Diaphragmatic Hernia (TOP-CDH)
Recruiting · NCT05201144 · Interventional (participants receive a specific treatment) · Lead sponsor: University of Utah
View the official record on ClinicalTrials.gov →Interventions studied
What this trial is about
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 a quaternary care center, Primary Children's Hospital (PCH). Of these neonates with PH, approximately 25% have been treated with off-label sildenafil. However, neither the PCH clinical care group nor others have developed/published a standardized approach for either initiating or discontinuing sildenafil therapy in this group of patients. Thus, the aim of this study is 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, the plan is to use this data to support a larger multicenter randomized trial targeting long-term cardiopulmonary outcomes of infants with CDH and post-repair PH.
Who can take part
Inclusion criteria
- Infants admitted to PCH NICU
- Diagnosis of congenital diaphragmatic hernia (CDH)
- Status post-surgical repair of diaphragmatic defect
- Has an echocardiogram 48-72 hours after repair with left ventricular eccentricity index (LVEI) ≥ 1.4
- Parental consent obtained within 24 hours after the above echocardiogram
Exclusion criteria
- Infants with CDH who do not undergo surgical repair
- Does not have an echocardiogram 48-72 hours post-repair
- Has LVEI \< 1.4 on above echocardiogram
- Has concurrent severe congenital heart defect that requires neonatal cardiac repair
- Has a documented sildenafil allergy
- Concurrent therapy with fluconazole at time of study drug initiation
- Inability to obtain parental consent within 24 hours of the echocardiogram
- Receiving extracorporeal membrane oxygenation (ECMO) at the time of the study
Where it is running
1 location listed across 1 US state.
- Primary Children's Hospital - Salt Lake City, Utah, United States