# Safety of Sildenafil in Premature Infants with Severe Bronchopulmonary Dysplasia

> **NIH NIH R33** · DUKE UNIVERSITY · 2022 · $2,307,686

## Abstract

Pulmonary hypertension is a deadly complication of bronchopulmonary dysplasia (BPD), the most common
pulmonary morbidity of prematurity. Up to 40% of premature infants with pulmonary hypertension and BPD will
die, and survivors suffer long-term morbidities. Despite these catastrophic consequences, no drugs are labeled
or evidence based for the prevention of pulmonary hypertension in this population. Sildenafil is a potent
pulmonary vasodilator approved by the FDA for the treatment of pulmonary hypertension in adults. Preclinical
BPD models suggest a beneficial effect on lung and vascular development, which may prevent pulmonary
hypertension. Real world evidence shows that neonatologists are increasingly using sildenafil in premature
infants despite lack of data on dosing, safety, and the exposure-response relationship. Led by Drs. Laughon, a
neonatologist and trialist, and Dr. Hornik, a pediatric cardiologist and clinical pharmacologist, our multi-
institutional and multidisciplinary team is dedicated to developing drugs for the prevention and treatment of
cardiopulmonary morbidities in infants, an area of urgent and unmet public health need. To meet this need, we
propose an adaptive, randomized, placebo controlled, double-blind, dose-escalation, prevention trial of 4
weeks of study drug (sildenafil: placebo 3:1 randomization) in 120 premature infants <29 weeks gestation with
severe BPD at risk for pulmonary hypertension at 30 clinical sites under IND (IND#112,374, holder Laughon).
Consistent with the goals of PAR-18-683, the proposed trial will provide the necessary dosing, safety, and
preliminary efficacy data needed to design a pivotal phase II/III trial, and move the drug forward toward labeling
for this indication. Leveraging partnerships with the NICHD funded Pediatric Trials Network, and the NCATS
funded Trial Innovation Network, we will translate several study design and operational innovations not
routinely utilized in infant trials including adaptive continual reassessment methods, risk-adjusted endpoints,
parent-engagement studios, and site based clinical optimization into the framework of an early phase study
conducted under regulatory oversight. These innovations will be implemented during the R61 award phase.
Our team has the expertise, access to participants, and environment necessary to conduct the proposed
research. In particular, we have completed a preliminary open-label pharmacokinetic study to identify safe
starting doses for this study, and conducted a cohort study to validate an echocardiogram based score as a
surrogate endpoint for pulmonary hypertension in premature infants, thereby avoiding the risks associated with
invasive cardiac catheterization in this vulnerable population. This preliminary work, combined with the
unparalleled experience of our team to complete early phase infant clinical trials on time and on budget, will
ensure the success of the proposed study, and directly improve the public health of premature ...

## Key facts

- **NIH application ID:** 10489371
- **Project number:** 5R33HL147833-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Christoph Hornik
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,307,686
- **Award type:** 5
- **Project period:** 2019-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10489371

## Citation

> US National Institutes of Health, RePORTER application 10489371, Safety of Sildenafil in Premature Infants with Severe Bronchopulmonary Dysplasia (5R33HL147833-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10489371. Licensed CC0.

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