A Trial of Phosphodiesterase-5 Inhibitor in Neonatal Congenital Diaphragmatic Hernia (TOP-CDH)
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.
Conditions:
🦠 Congenital Diaphragmatic Hernia 🦠 Pulmonary Hypertension
🗓️ Study Start (Actual) 15 September 2022
🗓️ Primary Completion (Estimated) March 2025
✅ Study Completion (Estimated) September 2025
👥 Enrollment (Estimated) 40
🔬 Study Type INTERVENTIONAL
📊 Phase PHASE2
Locations:
📍 Salt Lake City, Utah, United States

📋 Eligibility Criteria

Description

    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
Ages Eligible for Study: N/A to N/A (CHILD, ADULT, OLDER_ADULT)
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers: No

🗓️ Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

  • First Submitted 7 January 2022
  • First Submitted that Met QC Criteria 7 January 2022
  • First Posted 21 January 2022

Study Record Updates

  • Last Update Submitted that Met QC Criteria 6 May 2024
  • Last Update Posted 7 May 2024
  • Last Verified May 2024