A Trial of Phosphodiesterase-5 Inhibitor in Neonatal Congenital Diaphragmatic Hernia (TOP-CDH)
University of Utah
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 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.
Description
Congenital diaphragmatic hernia (CDH) occurs in approximately 1 in 3000 US live births, similar to the incidence seen within the Utah Birth Defects cohort. An early developmental diaphragmatic defect leads to herniation of abdominal contents into the thoracic cavity. Such visceral herniation 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. Survival among all liveborn infants is approximately 70% and has not changed in the past 20…
Eligibility
- Age range
- Not specified
- Sex
- All
- Healthy volunteers
- No
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 *…
Interventions
- DrugSildenafil Oral Suspension
Sildenafil citrate is a highly selective PDE-5 inhibitor found in pulmonary vascular smooth muscle cells. Sildenafil acts by increasing cGMP levels in the nitric oxide pathway, leading to smooth muscle relaxation and an anti-proliferative effect within the pulmonary vasculature.
- OtherPlacebo
Equal volume of placebo
Location
- Primary Children's HospitalSalt Lake City, Utah