ClinicalTrials.gg
RecruitingNCT05201144Updated Apr 4, 2025

A Trial of Phosphodiesterase-5 Inhibitor in Neonatal Congenital Diaphragmatic Hernia (TOP-CDH)

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

From the registry’s dates

  • Primary completion was expected by Mar 2026, 7 months ago, but the record still lists the study as recruiting.
  • Started Sep 2022; still recruiting 4 years 1 month later.

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Phase
Phase 2
Study type
Interventional
Enrollment
40
Allocation
Randomized
Sex
All
01

Where this study stands

Counted across the records on this site · 2026-11-14

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.

Planned enrollment
13th of 36
40 · median 21
Started
2022
with 2 others
Phase 2
3 of 45
1 open now
Primary completion
2026-03
later than 4 of 27 live
Registered
28th of 45
by date
Lead sponsor
4 of 45
University of Utah

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.

Hernias, Diaphragmatic, Congenital

86 studies on the registry are indexed under Hernias, Diaphragmatic, Congenital; 39 are open to participants now.

Browse Hernias, Diaphragmatic, Congenital studies →

Open to participants now

24 of the 45 studies in Hernias, Diaphragmatic, Congenital with a site in United States are open now. Recruiting first, the newest first:

18 more — sign in →

All 24 open studies →

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 →

Who these studies take

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.

The full table on the hub →

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Watch this landscapeDownload CSVNarrow it in search →With an account: a weekly mail of what changed among 45 studies in Hernias, Diaphragmatic, Congenital with a site in United States, or all of them as a file.
02

Study 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.

Read the detailed 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 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.

03

Conditions studied

  • Congenital Diaphragmatic Hernia
  • Pulmonary Hypertension
04

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
No

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.

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

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
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
40 participants (estimated)

Study arms

  • Active comparator
    Sildenafil citrate

    Sildenafil citrate 1mg/kg every 8 hours (PO or NG) for up to 14 days

    Drug: Sildenafil Oral Suspension

  • Placebo comparator
    Placebo

    Equivalent volume of Ora-sweet©/Ora-plus© every 8 hours (PO or NG) for up to 14 days

    Other: Placebo

Interventions

  • 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

06

What researchers measure

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

Other outcomes

  1. 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

  2. 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

07

Study locations

1 of 1 sites recruiting
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Started Sep 2022 (actual). Primary completion is estimated for Mar 2026, 42 months after the start.

How these figures are worked out, and which studies are left out of them.

Registered
Jan 7, 2022
First posted
Jan 21, 2022
StartActual
Sep 15, 2022
Primary completionEst.
Mar 31, 2026
CompletionEst.
Sep 30, 2026
Last update
Apr 4, 2025
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Apr 4, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT05201144
Lead sponsor
University of Utah
Responsible party
Michelle Yang (Principal Investigator, University of Utah) — Principal investigator
First posted
Jan 21, 2022
Start date
Sep 15, 2022
Primary completion
Mar 31, 2026 (estimated)
Completion
Sep 30, 2026 (estimated)
Last update
Apr 4, 2025

Study contacts

Carrie A Rau, RN
Contact
carrie.rau@hsc.utah.edu
801-213-3360

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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