A Phase 2 interventional study of Sildenafil Oral Suspension and Placebo in Congenital Diaphragmatic Hernia and Pulmonary Hypertension, sponsored by University of Utah. Recruiting at 1 site in United States. Per ClinicalTrials.gov, last updated 2025-04-04.
Sponsored by University of Utah · Phase 2, Interventional, and Treatment
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Among 45 studies in Hernias, Diaphragmatic, Congenital with a site in United States — 24 open to participants now, 28 under way, 2 of them phase 3. Hernias, Diaphragmatic, Congenital · United States.
Among the 45 studies in Hernias, Diaphragmatic, Congenital with a site in United States, this one is the 13th largest by planned enrollment of the 36 interventional ones that give a count, is one of 3 that started in 2022, is one of 3 in phase 2, reaches primary completion later than 4 of the 27 other live ones, and was the 28th registered.
86 studies on the registry are indexed under Hernias, Diaphragmatic, Congenital; 39 are open to participants now.
Browse Hernias, Diaphragmatic, Congenital studies →24 of the 45 studies in Hernias, Diaphragmatic, Congenital with a site in United States are open now. Recruiting first, the newest first:
Mauro H. Schenone · Sites in United States
Ages 18–50 · Women only
Dr Erin Perrone · Sites in United States
Ages 18+
Vincent Duron · Sites in United States
Ages 18+
The University of Texas Health Science Center, Houston · Sites in United States
Ages 0 mo–1 mo
Children's Hospital Medical Center, Cincinnati · Sites in United States
Ages 18–50 · Women only · Healthy volunteers
A study can be open while its sites in United States have not opened yet or have stopped. Only those recruiting at a site in United States →
Of the 32 Hernias, Diaphragmatic, Congenital studies recruiting now, 16 (50%) set no upper age limit and 16 (50%) stop at 75 or younger; 13 take children under 18; 6 take healthy volunteers.
This study: all sexes · no healthy volunteers.
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45 studies; the count open now beside each. This study's row is marked.
First in 2002; this study’s year is marked. 3 started in 2022.
By drug class, each counting the studies that test any of its medicines:
This study's planned enrollment of 40 is above the median of 30 across 62 interventional studies indexed under Hernias, Diaphragmatic, Congenital.
Median enrollment 21 across the 36 interventional studies, 51 across the 8 observational. Of the 14 that completed or were terminated, 5 (36%) have results posted.
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None of the 45 has an industry lead sponsor. The 10 most frequent:
University of Utah is the lead sponsor of 996 studies on the registry; 176 are open to participants now.
Of its 114 completed or terminated interventional studies of FDA-regulated products, 69 (61%) have results posted.
University of Utah has 4 studies filed under Hernias, Diaphragmatic, Congenital — fewer than ten, so there is no comparison to draw.
2 of the studies in Hernias, Diaphragmatic, Congenital with a site in United States that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT04583644Hanmin LeePilot Trial of Fetoscopic Endoluminal Tracheal Occlusion (FETO) in Severe Left Congenital Diaphragmatic Hernia (CDH) | 2027-04 |
| NCT00950118Columbia UniversityDiaphragmatic Hernia Research & Exploration, Advancing Molecular Science | 2027-09 |
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Among the 45 studies in Hernias, Diaphragmatic, Congenital with a site in United States, from their registry updates:
This tab as a report to print or save as PDF → With an account.
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.
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 years. A major contributor to morbidity and mortality of this neonatal cohort is persistent PH.
CDH-related PH is related to 1) arteriolar remodeling with increased vascular smooth muscularization leading to smaller diameters of the distal arterioles; 2) a hypodense vascular bed related to compromised lung growth; and 3) endothelial dysfunction resulting in increased vasoreactivity. Given this multifactorial nature of CDH-related PH, post-natal treatment is often challenging. Moreover, there is an increased risk of PH crises with post-operative inflammatory cascades and fluid shifts. Currently, optimal management of post-repair PH remains poorly investigated.
An important pulmonary vasodilatory cascade includes the nitric oxide pathway, which acts via increases in cyclic guanosine monophosphate (cGMP). 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. A multi-center trial evaluating the use of sildenafil in premature infants with bronchopulmonary dysplasia (NCT04447989) is currently underway. Pharmacokinetics of sildenafil in infants have previously been studied with a dosing range of 1mg/kg every 6-8 hours. In addition, sildenafil administration in the neonatal cohort appears safe and well-tolerated. Off-label use of sildenafil to treat CDH-related PH is increasing, despite limited evidence of efficacy in neonates with CDH. Use is based on the hypothesis that administering sildenafil post-hernia repair at a time when physiological changes are rapidly shifting may assist with pulmonary vascular relaxation to alleviate PH. Improvement in PH may ultimately benefit post-operative cardiorespiratory stability. Left ventricular eccentricity index (LVEI) is a non-invasive echocardiographic measure of such PH. LVEI is an objective measure that reflects the more subjective measure of left ventricular septal flattening. Its use decreases inter-observer variability and is a reliable assessment of neonatal PH. Elevated values of LVEI ≥ 1.4 are associated with right ventricular suprasystemic pressures. Normative values of LVEI in neonates without PH are ≤1.
Most neonates with CDH born within the Mountain West referral basin are managed at a quaternary care center, Primary Children's Hospital (PCH). PCH neonatal intensive care unit (NICU) averages 19 infants of CDH per year (range 12-24). Preliminary data shows that between 2007 and 2020, 60-85% of neonates with CDH managed at PCH manifest post-operative PH with LVEI values averaging between 1.4 to 2 on the post-repair echocardiogram. 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. Equipoise exists within the PCH clinical care group as the effectiveness of sildenafil use in neonates with CDH has not been well studied. 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, this data can be used to support a larger multicenter randomized trial targeting long-term cardiopulmonary outcomes of infants with CDH and post-repair PH.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Sildenafil citrate 1mg/kg every 8 hours (PO or NG) for up to 14 days
Drug: Sildenafil Oral Suspension
Equivalent volume of Ora-sweet©/Ora-plus© every 8 hours (PO or NG) for up to 14 days
Other: Placebo
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.
Equal volume of placebo
Change in Left Ventricular Eccentricity Index (LVEI) on echocardiogram after 14 days of study treatment compared to baseline echocardiogram as compared to placebo.
On echocardiogram, the septal position at end systole with either flattening or bowing into the left ventricle indicates elevated right ventricular pressures, a surrogate for elevated pulmonary arterial pressures and can be used to determine pulmonary hypertension (PH). LVEI has been shown to adequately quantify septal flattening when correlated to cardiac catheterization measures. Its use decreases inter-observer variability and is a reliable assessment of neonatal PH. Elevated values of LVEI ≥ 1.4 are associated with right ventricular half to suprasystemic pressures, consistent with PH. Normative values of LVEI in neonates without PH are ≤1.
Time frame: 14 days
Compare incidence of extracorporeal membrane oxygenation support (ECMO) between study and placebo groups
number of infants who required ECMO during the study treatment period will be compared between study and placebo groups
Time frame: 14 days
Compare incidence of death between study and placebo groups
number of infants who died during the study treatment period will be compared between study and placebo groups
Time frame: 14 days
Compare use of additional pulmonary vasodilators between study and placebo groups
Any pulmonary vasodilator (eg; inhaled nitric oxide, milrinone, etc) that is started after first study drug dose through 14 days will be counted and compared between study groups
Time frame: 14 days
Compare new onset hypotension between study and placebo groups
Number of infants experiencing new onset of systemic hypotension within 4 hours of study drug initiation, as defined by a greater than 20% decrease in mean arterial blood pressure from baseline value despite additional volume support up to 20 mL/kg and/or an increase in inotropic use will be compared between study and placebo groups
Time frame: 4 hours
Compare new onset of oliguria between study and placebo groups
Number of infants experiencing new oliguria of \< 1mL/kg/h for 12 hours unresponsive to fluid administration with onset within the first 36 hours of study drug
Time frame: 36 hours
Compare incidence of open-label sildenafil use during/after study period between study and placebo groups
Number of infants who receive open-label sildenafil during study period (protocol violation, but may happen due to clinical illness) or after study period through discharge will be compared between the study groups
Time frame: 3 months
Compare number of ventilator days between study and placebo group
Each calendar day in which the infant is intubated and on a ventilator will be counted from day of first study drug dose through day of last study drug dose
Time frame: 14 days
Plan to share: No
No publications or documents are linked to this record.
Started Sep 2022 (actual). Primary completion is estimated for Mar 2026, 42 months after the start.
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Studies of the drug tested here: Sildenafil
Hernias, Diaphragmatic, Congenital →