40 Participants Needed

Sildenafil for Diaphragmatic Hernia

CA
Overseen ByCarrie A Rau, RN
Age: Any Age
Sex: Any
Trial Phase: Phase 2
Sponsor: University of Utah
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 3 JurisdictionsThis treatment is already approved in other countries

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on fluconazole when starting the study drug.

Is sildenafil generally safe for humans?

Sildenafil, known as Viagra or Revatio, is generally safe for humans, with common mild side effects like headache, flushing, and indigestion. It has been well-tolerated in studies involving thousands of patients, including those with erectile dysfunction and pulmonary hypertension.12345

How is the drug sildenafil unique in treating diaphragmatic hernia?

Sildenafil is unique in treating diaphragmatic hernia because it can be administered intra-amniotically (directly into the amniotic fluid) to improve lung development and reduce pulmonary hypertension before birth, which is not a common approach with other treatments.15678

What data supports the effectiveness of the drug sildenafil for diaphragmatic hernia?

Research shows that sildenafil can help improve lung blood flow and reduce high blood pressure in the lungs (pulmonary hypertension) in infants with congenital diaphragmatic hernia. Studies in both humans and animals have demonstrated that sildenafil can stabilize and improve the condition by enhancing oxygenation and reducing the need for other treatments.56789

Are You a Good Fit for This Trial?

This trial is for newborns with a birth defect called congenital diaphragmatic hernia (CDH) who are in the NICU at Primary Children's Hospital. They must have had surgery to repair the hernia and show signs of pulmonary hypertension on an echocardiogram taken within 48-72 hours after surgery. Babies can't join if they didn't have surgery, need ECMO, or are allergic to sildenafil.

Inclusion Criteria

Infants admitted to PCH NICU
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
See 2 more

Exclusion Criteria

Newborns with a condition called CDH who have not had surgery to fix it.
Receiving extracorporeal membrane oxygenation (ECMO) at the time of the study
Does not have an echocardiogram 48-72 hours post-repair
See 5 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive sildenafil citrate 1mg/kg every 8 hours or placebo for up to 14 days

14 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including incidence of open-label sildenafil use and other outcomes

3 months

What Are the Treatments Tested in This Trial?

Interventions

  • Placebo
  • Sildenafil Oral Suspension
Trial Overview The study tests whether Sildenafil Oral Suspension, a drug that relaxes blood vessels in the lungs and is used off-label for neonatal pulmonary hypertension, is safe and effective for babies with CDH post-surgery. Some infants will receive this medication while others will get a placebo to compare outcomes.
How Is the Trial Designed?
2Treatment groups
Active Control
Placebo Group
Group I: Sildenafil citrateActive Control1 Intervention
Sildenafil citrate 1mg/kg every 8 hours (PO or NG) for up to 14 days
Group II: PlaceboPlacebo Group1 Intervention
Equivalent volume of Ora-sweet©/Ora-plus© every 8 hours (PO or NG) for up to 14 days

Sildenafil Oral Suspension is already approved in United States, European Union, Canada for the following indications:

🇺🇸
Approved in United States as Viagra for:
  • Erectile dysfunction
  • Pulmonary arterial hypertension
🇺🇸
Approved in United States as Revatio for:
  • Pulmonary arterial hypertension
🇪🇺
Approved in European Union as Viagra for:
  • Erectile dysfunction
  • Pulmonary arterial hypertension
🇪🇺
Approved in European Union as Revatio for:
  • Pulmonary arterial hypertension
🇨🇦
Approved in Canada as Viagra for:
  • Erectile dysfunction
  • Pulmonary arterial hypertension
🇨🇦
Approved in Canada as Revatio for:
  • Pulmonary arterial hypertension

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials
1,169
Recruited
1,623,000+

Published Research Related to This Trial

In a study of 44 neonates with congenital diaphragmatic hernia (CDH), intravenous sildenafil improved oxygenation in 42.3% of treated infants within the first 24 hours of life.
While sildenafil showed potential benefits in oxygenation and reduced pulmonary arterial pressure, it also led to a significant increase in vasopressor support, indicating a need for careful monitoring during treatment.
Continuous intravenous sildenafil as an early treatment in neonates with congenital diaphragmatic hernia.Kipfmueller, F., Schroeder, L., Berg, C., et al.[2019]
In a study of nine infants with congenital diaphragmatic hernia (CDH), intravenous (IV) sildenafil significantly improved oxygenation and reduced pulmonary artery pressure (PAP) after 72 to 96 hours of treatment.
The use of IV sildenafil also changed the flow dynamics of the patent ductus arteriosus (PDA), indicating a shift from right-to-left to left-to-right flow, which is beneficial for these infants' heart function.
Intravenous sildenafil in the management of pulmonary hypertension associated with congenital diaphragmatic hernia.Bialkowski, A., Moenkemeyer, F., Patel, N.[2016]
Intra-amniotic administration of sildenafil in pregnant rabbits shows rapid absorption into fetal organs, with maximum concentrations reached within 1 hour, indicating effective delivery to the fetus.
There was no evidence of organ toxicity in the fetuses after a single dose of sildenafil, confirming the safety of this method and supporting its potential use in treating pulmonary hypertension in congenital diaphragmatic hernia (CDH) cases.
Intra-amniotic sildenafil administration in rabbits: Safety, pharmacokinetics, organ distribution and histologic evaluation.Yoshida, S., Kreger, AM., Shaik, IH., et al.[2023]

Citations

Continuous intravenous sildenafil as an early treatment in neonates with congenital diaphragmatic hernia. [2019]
Intravenous sildenafil in the management of pulmonary hypertension associated with congenital diaphragmatic hernia. [2016]
Intra-amniotic sildenafil administration in rabbits: Safety, pharmacokinetics, organ distribution and histologic evaluation. [2023]
Treatment of rebound and chronic pulmonary hypertension with oral sildenafil in an infant with congenital diaphragmatic hernia. [2019]
Intra-amniotic sildenafil treatment improves lung blood flow and pulmonary hypertension in congenital diaphragmatic hernia rats. [2023]
Transplacental sildenafil rescues lung abnormalities in the rabbit model of diaphragmatic hernia. [2018]
Clinical safety of oral sildenafil citrate (VIAGRA) in the treatment of erectile dysfunction. [2022]
ALERT: Revatio is another brand name for sildenafil. [2017]
Tolerability and safety profile of sildenafil citrate (Viagra) in Latin American patient populations. [2015]
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