Sildenafil for Bronchopulmonary Dysplasia

(SILDI-SAFE Trial)

No longer recruiting at 30 trial locations

Overseen By Project Leader

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Christoph Hornik

Must not be taking: Vasopressors, Inhaled nitric oxide

Disqualifiers: Pulmonary hypertension, Congenital heart defect, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety of sildenafil (commonly used for erectile dysfunction and pulmonary hypertension) in treating severe bronchopulmonary dysplasia (BPD) in premature infants. BPD is a serious lung condition affecting preemies who require extra breathing support. The study will compare different doses of sildenafil to a placebo to evaluate its effectiveness in these infants. Babies born before 29 weeks who still need breathing assistance in the NICU may qualify for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if participants must stop taking their current medications, but it does exclude those who have recently taken certain drugs like sildenafil, vasopressors, inhaled nitric oxide, and milrinone. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that sildenafil is increasingly used in premature babies, despite limited safety information. Some studies suggest it might help reduce lung damage, offering hope for babies with bronchopulmonary dysplasia (BPD). Notably, one study found that sildenafil did not increase the risk of severe retinopathy of prematurity, a serious eye condition, in very low birth weight babies.

The FDA does not recommend sildenafil for children aged 1 to 17 with high blood pressure in the lungs, and no specific guidelines exist for its use in newborns. Researchers are still gathering safety data specifically for newborns. While sildenafil shows potential benefits, its safety in premature babies remains under study, and more information is needed. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for BPD?

Most treatments for bronchopulmonary dysplasia focus on supportive care like oxygen therapy or mechanical ventilation. Unlike these standard approaches, sildenafil is unique because it targets pulmonary hypertension, a condition that often accompanies bronchopulmonary dysplasia, by relaxing blood vessels in the lungs to improve blood flow. Researchers are excited about sildenafil because it has the potential to directly address a root cause of the condition rather than just alleviating symptoms. Additionally, sildenafil's different dosages and delivery methods (both IV and enteral) allow for flexibility in treating varying severities of the condition. This innovative approach offers hope for more effective management of bronchopulmonary dysplasia in infants.

What evidence suggests that sildenafil might be an effective treatment for bronchopulmonary dysplasia?

This trial will compare sildenafil with a placebo to evaluate its effects on babies with severe bronchopulmonary dysplasia (BPD), a lung condition. Research has shown that sildenafil might improve breathing and lower pressure in the lung arteries. One study suggested it might reduce lung damage and support healthy lung blood vessels. Early experiences indicate that sildenafil could be effective for babies with BPD and high blood pressure in the lungs. However, more detailed studies are needed to confirm these benefits. ^{1 3 6 7 8}

Who Is on the Research Team?

Christoph Hornik, MD

Principal Investigator

Duke UMC

Matt Laughon, MD

Principal Investigator

UNC

Are You a Good Fit for This Trial?

This trial is for premature infants in NICUs with severe bronchopulmonary dysplasia. Eligible babies are 32-44 weeks postmenstrual age, born before 29 weeks gestation, and need respiratory support. Parents must consent to participate. Infants can't join if they've had certain heart defects, sickle cell disease, recent vasopressors or nitric oxide use, high liver enzymes, or known sildenafil allergy.

Inclusion Criteria

Documented informed consent from parent or guardian, prior to study procedures

I am on a breathing machine or CPAP depending on my baby's age in weeks.

I was born before reaching 29 weeks of pregnancy.

Exclusion Criteria

I have not taken milrinone in the last 24 hours.

I have sickle cell disease.

Participant will be reassessed prior to dosing to reconfirm eligibility criteria.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Treatment

Participants receive sildenafil or placebo every 8 hours for 28 days

4 weeks

Daily monitoring in NICU

Weaning

Participants are weaned off the study drug following the treatment period

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Sildenafil

Trial Overview The study tests the safety of Sildenafil compared to a placebo in helping premature infants with severe lung problems (BPD). It's randomized (babies are put into groups by chance), double-masked (neither doctors nor parents know which treatment the baby gets), and dose levels increase over time.

How Is the Trial Designed?

Group I: Cohort 1, sildenafil Active Control 1 Intervention

Sildenafil (0.5 mg/kg IV or 1 mg/kg enteral) every 8 hours for 28 days

Group II: Cohort 3, sildenafil Active Control 1 Intervention

Sildenafil (2 mg/kg IV or 4 mg/kg enteral) every 8 hours for 28 days

Group III: Cohort 2, sildenafil Active Control 1 Intervention

Sildenafil (1 mg/kg IV or 2 mg/kg enteral) every 8 hours for 28 days

Group IV: Cohort 2, placebo Placebo Group 1 Intervention

Placebo (IV or enteral) every 8 hours for 28 days

Group V: Cohort 3, placebo Placebo Group 1 Intervention

Placebo (IV or enteral) every 8 hours for 28 days

Group VI: Cohort 1, placebo Placebo Group 1 Intervention

Placebo (IV or enteral) every 8 hours for 28 days

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

Approved in United States as Viagra for:

• Erectile dysfunction
• Pulmonary arterial hypertension

Approved in European Union as Viagra for:

• Erectile dysfunction
• Pulmonary arterial hypertension

Approved in United States as Revatio for:

• Pulmonary arterial hypertension

Approved in Canada as Sildenafil for:

• Erectile dysfunction
• Pulmonary arterial hypertension

Approved in Japan as Sildenafil for:

• Erectile dysfunction
• Pulmonary arterial hypertension

Who Is Running the Clinical Trial?

Christoph Hornik

Lead Sponsor

Trials

1

Recruited

120+

Christoph P Hornik, MD MPH

Lead Sponsor

Trials

3

Recruited

280+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

University of North Carolina, Chapel Hill

Collaborator

Trials

1,588

Recruited

4,364,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6681505/

Sildenafil for bronchopulmonary dysplasia and pulmonary ... Our results show that sildenafil appears to be associated with improvements in estimates of PAP and respiratory scores; however, sildenafil showed no effect on ...

2. mdpi.com mdpi.com/2227-9067/10/8/1397

Efficacy of Sildenafil in Infants with Bronchopulmonary ... We also found improvement in clinical outcomes at 14 weeks following sildenafil treatment initiation. However, since there is no control arm in ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2451865422001429

Safety of sildenafil in premature infants at risk ... Sildenafil reduces lung injury and preserves normal vasculature in preclinical models, and improves outcomes in children with pulmonary hypertension, and thus ...

4. scholars.duke.edu scholars.duke.edu/individual/pub1468839

Safety of sildenafil in premature infants with severe ... Sildenafil may therefore prevent the development of pulmonary hypertension associated with lung disease of prematurity by reducing pulmonary ...

5. publications.aap.org publications.aap.org/hospitalpediatrics/article/6/1/27/26295/Sildenafil-Treatment-of-Infants-With

Sildenafil Treatment of Infants With Bronchopulmonary ... Early clinical experience indicates that sildenafil treatment may be efficacious for infants with BPD-PH, with evidence suggesting that ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04447989

Safety of Sildenafil in Premature Infants With Severe ... This is a multicenter, randomized, placebo-controlled, sequential dose-escalating, double-masked, safety study of sildenafil in premature infants.

7. nature.com nature.com/articles/jp2015201

More safety data: what about efficacy of sildenafil? The study did not show an increased risk for severe retinopathy of prematurity for very low birth weight infants on sildenafil.

8. bmcpediatr.biomedcentral.com bmcpediatr.biomedcentral.com/articles/10.1186/s12887-020-02453-7

Safety of sildenafil in premature infants with severe ... The FDA does not recommend sildenafil for PH in children 1 to 17 years of age and there are no recommendations regarding its use in neonates and ...