Safety of Sildenafil in Premature Infants With Severe Bronchopulmonary Dysplasia (SILDI-SAFE)

January 7, 2026 updated by: Christoph Hornik
This is a multicenter, randomized, placebo-controlled, sequential dose-escalating, double-masked, safety study of sildenafil in premature infants (inpatient in Neonatal Intensive Care Units (NICUs)) with severe bronchopulmonary dysplasia (BPD).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Screening/Baseline

Research staff will document informed consent from the parent/guardian for all participants who satisfy eligibility criteria. The following information will be recorded in the case report form (eCRF) from the clinical medical record:

  1. Participant demographics, including birth weight and gestational age at birth
  2. Maternal race/ethnicity
  3. Medical history
  4. Physical examination, including actual weight
  5. All mean arterial pressure (MAP) obtained in the 24 hours before the first dose
  6. Concomitant medications (within 24 hours prior to start of study drug)
  7. Respiratory assessment
  8. Laboratory evaluations
  9. Echocardiogram: If performed per local standard of care < 14 days prior to start of study drug, a study-specific echocardiogram need not be repeated. If not performed per local standard of care < 14 days prior to start of study drug, an echocardiogram will be required to confirm eligibility.
  10. Cardiac catheterization reports, if performed per local standard of care < 14 days prior to start of study drug.
  11. Adverse events following initial study-specific procedure

Treatment Period

The treatment period will include Days 1-28 or last day of study drug if early withdrawal of study drug. The following information will be collected and recorded while the participant is on study drug:

  1. Actual weight on study Days 7 (± 1 day), 14 (± 1 day), 21 (± 1 day), and 28 (± 1 day) of study drug administration
  2. Date, time, amount, and route of study drug dose
  3. All concomitant medications

  4. MAP

    A. All MAP values obtained 24 hours after the first dose of study drug regardless of administration route.

    B. MAP values will be obtained at a minimum at the following time points i. Prior to the first dose of study drug or dose escalation: 2 hours (± 5 minutes), 1 hour (± 5 minutes), and 15 minutes (± 5 minutes) ii. If administration route is IV:

    1. During and following the first dose of study drug or dose escalation: MAP at start of infusion, every 15 minutes (± 5 minutes) during infusion, at end of infusion (inclusive of flush) (± 5 minutes), at 15 and 30 minutes (± 5 minutes) after end of infusion, hourly (± 15 minutes) for 4 hours, and once in the remaining 2 hours prior to the next dose.
    2. For subsequent IV doses, the lowest valid MAP value should be recorded daily while on study drug.

    iii. If the administration route is enteral:

    1. During and following the first dose of study drug or dose escalation: MAP at start of enteral administration, then every 15 minutes (± 5 minutes) for 90 minutes (1.5 hours), then every 30 minutes (± 5 minutes) for 60 minutes (1 hour), then hourly (± 15 minutes) for 4 hours, then once in the remaining 2 hours prior to the next dose.
    2. For subsequent enteral doses, the lowest valid MAP value should be recorded daily while on study drug.
  5. Respiratory assessment, weekly
  6. Laboratory evaluations, at least every other week
  7. Echocardiograms and cardiac catheterization reports, if performed per local standard of care
  8. Pharmacokinetic (PK) sampling (after Day 7)
  9. Adverse events

Weaning Period (Cohorts 2 and 3)

The weaning period will begin following Day 28 of study drug or, following the last day of study drug if participant was withdrawn from study drug prior to Day 28 and the dose escalated to ≥ 0.5 mg/kg IV or ≥ 1 mg/kg enteral.

The following information will be collected and recorded while the participant is weaning from study drug:

  1. Date, time, amount and route of study drug dose
  2. MAP (the lowest MAP value on last day of wean should be recorded).
  3. Respiratory assessment on last day of wean
  4. Echocardiogram and cardiac catheterization reports, if performed per local standard of care
  5. Adverse events

Follow-up Period

The follow-up period will include Days 1-28 after the last study drug dose; last study drug dose may occur prior to Day 28 for those participants who withdraw from study drug early; on Day 28 for those participants who complete the full treatment period; or after last weaning dose for those participants who require weaning. The following information will be reported in electronic data capture system (EDC) at Day 1 (+ 2 days) and 14 (± 2days) of the follow-up period (or days closest to and after Day 1 and 14, if >1 assessment is available), except for MAP, adverse events (AEs), and serious adverse events (SAEs) (which will be reported from Days 1-28 post last study drug dose) and standard of care echocardiograms or cardiac catheterization reports:

  1. Physical examination, including actual weight
  2. MAP (the lowest valid MAP value on follow-up Day 1, 14, 21, and 28 should be recorded).
  3. Respiratory assessment
  4. Laboratory evaluations
  5. Echocardiogram on follow-up Day 1 (+2 days). If performed per local standard of care, a study-specific echocardiogram need not be repeated. If not performed per local standard of care on Day 1 (+2 days) of the follow-up period, an echocardiogram will need to be performed.
  6. Echocardiograms and cardiac catheterization reports, if performed per local standard of care (during follow-up Days 1-28)
  7. Adverse events and SAEs (during follow-up Days 1-28)

Final Study Assessment

Final study assessment will occur at the time of discharge or transfer. The following information will be collected:

  1. Physical examination, including actual weight
  2. Respiratory assessment
  3. Echocardiogram and cardiac catheterization reports, if performed per local standard of care on the day of discharge or transfer or up to 2 days prior.
  4. Global rank
  5. Discharge information A. Discharge or transfer B. Death C. Duration of hospitalization
  6. Record if treatment for retinopathy of prematurity (ROP) was required

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
125

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72202
        • Arkansas Children's Research Institute
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas Medical Sciences
    • California
      • San Diego, California, United States, 92123
        • Rady Children's Hospital and Health Center
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20010
        • Childrens National Medical Center
    • Florida
      • Jacksonville, Florida, United States, 32209
        • University of Florida Jacksonville Shands Medical Center
      • Jacksonville, Florida, United States, 32209
        • Wolfson Children's Hospital
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory Children's Center
    • Illinois
      • Chicago, Illinois, United States, 60611
        • University of Illinois at Chicago
      • Chicago, Illinois, United States, 60611-2605
        • Lurie Children's Hospital
    • Kentucky
      • Lexington, Kentucky, United States, 40506
        • University of Kentucky Chandler Medical Center
      • Louisville, Kentucky, United States, 40202
        • University of Louisville School of Medicine
    • Louisiana
      • New Orleans, Louisiana, United States, 70115
        • Ochsner Baptist Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Childrens Mercy Hospital
    • Nevada
      • Las Vegas, Nevada, United States, 89102
        • Children's Hospital of Nevada at University Medical Center
    • New York
      • Rochester, New York, United States, 14642
        • University of Rochester School of Medicine Children's Hospital
      • Valhalla, New York, United States, 10595
        • Westchester Medical Center - New York Medical College
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University Of NC At Chapel Hill
      • Greenville, North Carolina, United States, 27858
        • East Carolina University
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Rainbow Babies and Childrens Hospital
    • Tennessee
      • Memphis, Tennessee, United States, 38163
        • University of Tennessee Health Science Center
    • Texas
      • Austin, Texas, United States, 78723
        • University of Texas Health
      • Houston, Texas, United States, 77054
        • Women's Hospital of Texas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 2 years (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Documented informed consent from parent or guardian, prior to study procedures
  2. < 29 weeks gestational age at birth
  3. 32-44 weeks postmenstrual age

  4. Receiving respiratory support at enrollment:

    • If 32 0/7-35 6/7 weeks postmenstrual age: mechanical ventilation (high frequency or conventional)
    • If 36 0/7-44 6/7 weeks postmenstrual age: mechanical ventilation (high frequency or conventional) OR continuous positive airway pressure (CPAP)

Note:

  • Criteria 3 and 4 define severe BPD for the purposes of this study

  • CPAP is defined as any of the following:

    • Nasal cannula > 2 liters per minute (LPM)
    • Nasal continuous positive airway pressure (NCPAP)
    • Nasal intermittent positive pressure ventilation (NIPPV)
    • Noninvasive neurally adjusted ventilatory assist (NAVA)
    • Any other device designed to provide positive pressure through a nasal device (e.g., RAM cannula, etc.)

Exclusion Criteria:

  1. Previous enrollment and dosing in this study, protocol number (NHLBI-2019-SIL), "Safety of Sildenafil in Premature Infants with Severe Bronchopulmonary Dysplasia (BPD)"
  2. Previous exposure to sildenafil within 7 days prior to randomization*
  3. Previous exposure to vasopressors within 24 hours prior to randomization*
  4. Previous exposure to inhaled nitric oxide within 24 hours prior to randomization*
  5. Previous exposure to milrinone within 24 hours prior to randomization*
  6. Evidence of pulmonary hypertension or moderate/large patent ductus arteriosus (PDA) on the most recent echocardiogram performed within 14 days prior to randomization
  7. Known major congenital heart defect requiring medical or surgical intervention in the neonatal period
  8. Known allergy to sildenafil
  9. Known sickle cell disease
  10. Aspartate aminotransferase (AST) > 225 U/L < 72 hours prior to randomization
  11. Alanine aminotransferase (ALT) > 150 U/L < 72 hours prior to randomization

  12. Any condition that would make the participant, in the opinion of the investigator, unsuitable for the study.

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Cohort 1, sildenafil
Sildenafil (0.5 mg/kg IV or 1 mg/kg enteral) every 8 hours for 28 days
Drug: Sildenafil
Sildenafil citrate injection or powder for suspension
Other Names:
  • Revatio
Placebo Comparator: Cohort 1, placebo
Placebo (IV or enteral) every 8 hours for 28 days
Drug: Placebo
dextrose 5%
Other Names:
  • Dextrose 5%
Active Comparator: Cohort 2, sildenafil
Sildenafil (1 mg/kg IV or 2 mg/kg enteral) every 8 hours for 28 days
Drug: Sildenafil
Sildenafil citrate injection or powder for suspension
Other Names:
  • Revatio
Placebo Comparator: Cohort 2, placebo
Placebo (IV or enteral) every 8 hours for 28 days
Drug: Placebo
dextrose 5%
Other Names:
  • Dextrose 5%
Active Comparator: Cohort 3, sildenafil
Sildenafil (2 mg/kg IV or 4 mg/kg enteral) every 8 hours for 28 days
Drug: Sildenafil
Sildenafil citrate injection or powder for suspension
Other Names:
  • Revatio
Placebo Comparator: Cohort 3, placebo
Placebo (IV or enteral) every 8 hours for 28 days
Drug: Placebo
dextrose 5%
Other Names:
  • Dextrose 5%

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Safety Based Upon Number of Participants With Hypotension
Time Frame: 28 days post last dose of study drug, up to 9 weeks

Safety as determined by incidence of hypotension experienced by the participants through 28 days post last dose of study drug.

Hypotension will be defined as any clinically significant low blood pressure event deemed by the treating physician to require intervention with a fluid bolus or the initiation or escalation of inotropic, vasopressor, or systemic steroid therapy with the specific intent to raise blood pressure.
28 days post last dose of study drug, up to 9 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Central Volume of Distribution (Vc) Population Pharmacokinetics (popPK)
Time Frame: Following the completion of 7 days (168 hours) of study drug administration
Following the completion of 7 days (168 hours) of study drug administration
Peripheral Volume of Distribution (Vp) Population Pharmacokinetics (popPK)
Time Frame: Following the completion of 7 days (168 hours) of study drug administration
Following the completion of 7 days (168 hours) of study drug administration
Clearance Population Pharmacokinetics (popPK)
Time Frame: Following the completion of 7 days (168 hours) of study drug administration
Following the completion of 7 days (168 hours) of study drug administration
Half-life Population Pharmacokinetics (popPK)
Time Frame: Following the completion of 7 days (168 hours) of study drug administration
Following the completion of 7 days (168 hours) of study drug administration
Peak Plasma Concentration Population Pharmacokinetics (popPK)
Time Frame: Following the completion of 7 days (168 hours) of study drug administration
Following the completion of 7 days (168 hours) of study drug administration

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants at Each Global Rank
Time Frame: 28 days post last dose of study drug, up to 9 weeks
Global rank is defined as clinically significant events ranked in order of decreasing perceived severity. Rank descriptions are presented from most to least severe.
28 days post last dose of study drug, up to 9 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Christoph Hornik

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Heart, Lung, and Blood Institute (NHLBI)
University of North Carolina, Chapel Hill

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Christoph Hornik, MD, Duke UMC
  • Principal Investigator: Matt Laughon, MD, UNC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 27, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 12, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 15, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 22, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 24, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 25, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 26, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 7, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Pro00104901
  • 1R61HL147833-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

There is no plan to make IPD available to other researchers

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Conditions

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Dietary Supplements

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Locations

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