Bronchopulmonary Dysplasia of NewbornPhase 2SILDI-SAFENCT04447989
Safety of Sildenafil in Premature Infants With Severe Bronchopulmonary Dysplasia
A Phase 2 study testing Sildenafil in people with Bronchopulmonary Dysplasia of Newborn, run by Christoph Hornik at 25 sites in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages Up to 29 weeks
- Conditions the study is for
- Bronchopulmonary Dysplasia of Newborn
- What is being tested?
- Sildenafil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 125 participants
- Where
- 25 sitesUnited States
- Study dates
- 27 May 2021to 15 Jan 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 29 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Documented informed consent from parent or guardian, prior to study procedures
- < 29 weeks gestational age at birth
- 32-44 weeks postmenstrual age
- 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)
Show all 14Show fewer
- 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.)
Who cannot join
- Previous enrollment and dosing in this study, protocol number (NHLBI-2019-SIL), "Safety of Sildenafil in Premature Infants with Severe Bronchopulmonary Dysplasia (BPD)"
- Previous exposure to sildenafil within 7 days prior to randomization*
- Previous exposure to vasopressors within 24 hours prior to randomization*
- Previous exposure to inhaled nitric oxide within 24 hours prior to randomization*
- Previous exposure to milrinone within 24 hours prior to randomization*
- Evidence of pulmonary hypertension or moderate/large patent ductus arteriosus (PDA) on the most recent echocardiogram performed within 14 days prior to randomization
Show all 13Show fewer
- Known major congenital heart defect requiring medical or surgical intervention in the neonatal period
- Known allergy to sildenafil
- Known sickle cell disease
- Aspartate aminotransferase (AST) > 225 U/L < 72 hours prior to randomization
- Alanine aminotransferase (ALT) > 150 U/L < 72 hours prior to randomization
- 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.
Trial locations and contacts
25 sites in 1 country.
25 sites in 1 country
United States25 sites
Emory Children's Center
Atlanta, Georgia, 30322
University of Texas Health
Austin, Texas, 78723
Boston Children's Hospital
Boston, Massachusetts, 02115
University of NC at Chapel Hill
Chapel Hill, North Carolina, 27599
Lurie Children's Hospital
Chicago, Illinois, 60611-2605
University of Illinois at Chicago
Chicago, Illinois, 60611
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106
East Carolina University
Greenville, North Carolina, 27858
Women's Hospital of Texas
Houston, Texas, 77054
University of Mississippi Medical Center
Jackson, Mississippi, 39216
University of Florida Jacksonville Shands Medical Center
Jacksonville, Florida, 32209
Wolfson Children's Hospital
Jacksonville, Florida, 32209
Childrens Mercy Hospital
Kansas City, Missouri, 64108
Children's Hospital of Nevada at University Medical Center
Las Vegas, Nevada, 89102
University of Kentucky Chandler Medical Center
Lexington, Kentucky, 40506
Arkansas Children's Research Institute
Little Rock, Arkansas, 72202
University of Arkansas Medical Sciences
Little Rock, Arkansas, 72205
University of Louisville School of Medicine
Louisville, Kentucky, 40202
University of Tennessee Health Science Center
Memphis, Tennessee, 38163
Ochsner Baptist Medical Center
New Orleans, Louisiana, 70115
University of Rochester School of Medicine Children's Hospital
Rochester, New York, 14642
Rady Children's Hospital and Health Center
San Diego, California, 92123
Westchester Medical Center - New York Medical College
Valhalla, New York, 10595
Childrens National Medical Center
Washington D.C., District of Columbia, 20010
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
About this study
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).
Read the 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:
- Participant demographics, including birth weight and gestational age at birth
- Maternal race/ethnicity
- Medical history
- Physical examination, including actual weight
- All mean arterial pressure (MAP) obtained in the 24 hours before the first dose
- Concomitant medications (within 24 hours prior to start of study drug)
- Respiratory assessment
- Laboratory evaluations
- 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.
- Cardiac catheterization reports, if performed per local standard of care < 14 days prior to start of study drug.
- 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:
- Actual weight on study Days 7 (± 1 day), 14 (± 1 day), 21 (± 1 day), and 28 (± 1 day) of study drug administration
- Date, time, amount, and route of study drug dose
- All concomitant medications
- MAP
- All MAP values obtained 24 hours after the first dose of study drug regardless of administration route.
- 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:
- 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.
- For subsequent IV doses, the lowest valid MAP value should be recorded daily while on study drug. iii. If the administration route is enteral:
- 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.
- For subsequent enteral doses, the lowest valid MAP value should be recorded daily while on study drug.
- Respiratory assessment, weekly
- Laboratory evaluations, at least every other week
- Echocardiograms and cardiac catheterization reports, if performed per local standard of care
- Pharmacokinetic (PK) sampling (after Day 7)
- 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:
- Date, time, amount and route of study drug dose
- MAP (the lowest MAP value on last day of wean should be recorded).
- Respiratory assessment on last day of wean
- Echocardiogram and cardiac catheterization reports, if performed per local standard of care
- 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:
- Physical examination, including actual weight
- MAP (the lowest valid MAP value on follow-up Day 1, 14, 21, and 28 should be recorded).
- Respiratory assessment
- Laboratory evaluations
- 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.
- Echocardiograms and cardiac catheterization reports, if performed per local standard of care (during follow-up Days 1-28)
- 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:
- Physical examination, including actual weight
- Respiratory assessment
- 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.
- Global rank
- Discharge information A. Discharge or transfer B. Death C. Duration of hospitalization
- Record if treatment for retinopathy of prematurity (ROP) was required
- Conditions
- Bronchopulmonary Dysplasia of Newborn
- Being tested
- Sildenafil, Placebo
- Medical subject headings
- Bronchopulmonary Dysplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SildenafilDrug
Also called Revatio
Sildenafil citrate injection or powder for suspension
PlaceboDrug
Also called Dextrose 5%
dextrose 5%
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1, sildenafil | Active comparator | Sildenafil (0.5 mg/kg IV or 1 mg/kg enteral) every 8 hours for 28 days Receives: Drug: Sildenafil |
| Cohort 1, placebo | Placebo comparator | Placebo (IV or enteral) every 8 hours for 28 days Receives: Drug: Placebo |
| Cohort 2, sildenafil | Active comparator | Sildenafil (1 mg/kg IV or 2 mg/kg enteral) every 8 hours for 28 days Receives: Drug: Sildenafil |
| Cohort 2, placebo | Placebo comparator | Placebo (IV or enteral) every 8 hours for 28 days Receives: Drug: Placebo |
| Cohort 3, sildenafil | Active comparator | Sildenafil (2 mg/kg IV or 4 mg/kg enteral) every 8 hours for 28 days Receives: Drug: Sildenafil |
| Cohort 3, placebo | Placebo comparator | Placebo (IV or enteral) every 8 hours for 28 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety Based Upon Number of Participants With Hypotension
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.
Measured: 28 days post last dose of study drug, up to 9 weeks
Secondary outcomes (5)
Central Volume of Distribution (Vc) Population Pharmacokinetics (popPK)
Measured: Following the completion of 7 days (168 hours) of study drug administration
Peripheral Volume of Distribution (Vp) Population Pharmacokinetics (popPK)
Measured: Following the completion of 7 days (168 hours) of study drug administration
Clearance Population Pharmacokinetics (popPK)
Measured: Following the completion of 7 days (168 hours) of study drug administration
Half-life Population Pharmacokinetics (popPK)
Measured: Following the completion of 7 days (168 hours) of study drug administration
Peak Plasma Concentration Population Pharmacokinetics (popPK)
Measured: Following the completion of 7 days (168 hours) of study drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2020
- Study start27 May 2021
- Primary completion12 Dec 2024
- Study completion15 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Bronchopulmonary Dysplasia of NewbornStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Premature infants with severe BPD (inpatient in neonatal intensive care units) will be randomized in a dose escalating approach 3:1 (sildenafil: placebo) sequentially, into each of 3 cohorts. There will be approximately 40 randomized and dosed participants in each cohort for a total of up to 120 participants.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 125 participants (actual)
Sponsor and investigators
- Lead sponsor
- Christoph Hornik
- Sponsor type
- University, hospital or other
- Collaborators
- University of North Carolina, Chapel Hill, National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor-investigator, Christoph Hornik, Duke University
- Investigators
- Christoph Hornik, MD, Principal investigator, Duke UMCMatt Laughon, MD, Principal investigator, UNC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04447989
- Sponsor's protocol ID
- Pro00104901
- Other IDs
- 1R61HL147833-01
- Acronym
- SILDI-SAFE
- Status last verified
- Jan 2026
- First submitted
- 22 Jun 2020
- Last updated
- 26 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: There is no plan to make IPD available to other researchers
Publications
Gonzalez D, Laughon MM, Smith PB, Ge S, Ambalavanan N, Atz A, Sokol GM, Hornik CD, Stewart D, Mundakel G, Poindexter BB, Gaedigk R, Mills M, Cohen-Wolkowiez M, Martz K, Hornik CP; Best Pharmaceuticals for Children Act - Pediatric Trials Network Steering Committee. Population pharmacokinetics of sildenafil in extremely premature infants. Br J Clin Pharmacol. 2019 Dec;85(12):2824-2837. doi: 10.1111/bcp.14111. Epub 2019 Dec 15.
PubMed 31475367Stoll BJ, Hansen NI, Bell EF, Walsh MC, Carlo WA, Shankaran S, Laptook AR, Sanchez PJ, Van Meurs KP, Wyckoff M, Das A, Hale EC, Ball MB, Newman NS, Schibler K, Poindexter BB, Kennedy KA, Cotten CM, Watterberg KL, D'Angio CT, DeMauro SB, Truog WE, Devaskar U, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Trends in Care Practices, Morbidity, and Mortality of Extremely Preterm Neonates, 1993-2012. JAMA. 2015 Sep 8;314(10):1039-51. doi: 10.1001/jama.2015.10244.
PubMed 26348753Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001 Jun;163(7):1723-9. doi: 10.1164/ajrccm.163.7.2011060. No abstract available.
PubMed 11401896Khemani E, McElhinney DB, Rhein L, Andrade O, Lacro RV, Thomas KC, Mullen MP. Pulmonary artery hypertension in formerly premature infants with bronchopulmonary dysplasia: clinical features and outcomes in the surfactant era. Pediatrics. 2007 Dec;120(6):1260-9. doi: 10.1542/peds.2007-0971.
PubMed 18055675Morrow CB, McGrath-Morrow SA, Collaco JM. Predictors of length of stay for initial hospitalization in infants with bronchopulmonary dysplasia. J Perinatol. 2018 Sep;38(9):1258-1265. doi: 10.1038/s41372-018-0142-7. Epub 2018 Jun 8.
PubMed 29880793Jackson W, Hornik CP, Messina JA, Guglielmo K, Watwe A, Delancy G, Valdez A, MacArthur T, Peter-Wohl S, Smith PB, Tolia VN, Laughon MM. In-hospital outcomes of premature infants with severe bronchopulmonary dysplasia. J Perinatol. 2017 Jul;37(7):853-856. doi: 10.1038/jp.2017.49. Epub 2017 Apr 6.
PubMed 28383537Poets CF, Lorenz L. Prevention of bronchopulmonary dysplasia in extremely low gestational age neonates: current evidence. Arch Dis Child Fetal Neonatal Ed. 2018 May;103(3):F285-F291. doi: 10.1136/archdischild-2017-314264. Epub 2018 Jan 23.
PubMed 29363502Tyson JE, Wright LL, Oh W, Kennedy KA, Mele L, Ehrenkranz RA, Stoll BJ, Lemons JA, Stevenson DK, Bauer CR, Korones SB, Fanaroff AA. Vitamin A supplementation for extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. N Engl J Med. 1999 Jun 24;340(25):1962-8. doi: 10.1056/NEJM199906243402505.
PubMed 10379020Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, Solimano A, Tin W; Caffeine for Apnea of Prematurity Trial Group. Caffeine therapy for apnea of prematurity. N Engl J Med. 2006 May 18;354(20):2112-21. doi: 10.1056/NEJMoa054065.
PubMed 16707748Doyle LW, Ehrenkranz RA, Halliday HL. Early (< 8 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants. Cochrane Database Syst Rev. 2014 May 13;(5):CD001146. doi: 10.1002/14651858.CD001146.pub4.
PubMed 24825456Jackson WM, Foote HP, Stephenson N, Kemp SM, Moore RT, Nitkin CR, Stewart D, Pryhuber GS, Berger JT, Shukla A, England A, Ford SM, Parton LA, Check JF, Hanna MH, Lagoski M, Krishnan R, Leeman KT, Vyas-Read S, Hudak ML, Katheria AC, Pillers DM, Ji J, Banfro F, Nelin LD, McCulloch M, Ahmad K, Laughon MM, Hornik CP; SILDI-SAFE Study Group. Safety of Sildenafil in Premature Infants with Severe Bronchopulmonary Dysplasia (SILDI-SAFE): A Randomized Controlled Trial. J Pediatr. 2026 Aug;295:115147. doi: 10.1016/j.jpeds.2026.115147. Epub 2026 May 7.
PubMed 42105936Schneider S, Bailey M, Spears T, Esther CR Jr, Laughon MM, Hornik CP, Jackson W. Safety of sildenafil in premature infants with severe bronchopulmonary dysplasia (SILDI-SAFE): a multicenter, randomized, placebo-controlled, sequential dose-escalating, double-masked, safety study. BMC Pediatr. 2020 Dec 14;20(1):559. doi: 10.1186/s12887-020-02453-7.
PubMed 33317479
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety of Sildenafil in Premature Infants With Severe Bronchopulmonary Dysplasia
- ClinicalTrials.gov ID
- NCT04447989
- Acronym / sponsor ID
- SILDI-SAFE / Pro00104901
- Conditions
- Bronchopulmonary Dysplasia of Newborn
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 125 participants (actual)
- Lead sponsor
- Christoph HornikUniversity, hospital or other
- Collaborators
- University of North Carolina, Chapel Hill, National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 27 May 2021 (actual)
- Primary completion
- 12 Dec 2024 (actual)
- Study completion
- 15 Jan 2025 (actual)
- First posted
- 25 Jun 2020 (actual)
- Results
- Posted 26 Jan 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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:
- Participant demographics, including birth weight and gestational age at birth
- Maternal race/ethnicity
- Medical history
- Physical examination, including actual weight
- All mean arterial pressure (MAP) obtained in the 24 hours before the first dose
- Concomitant medications (within 24 hours prior to start of study drug)
- Respiratory assessment
- Laboratory evaluations
- 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.
- Cardiac catheterization reports, if performed per local standard of care < 14 days prior to start of study drug.
- 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:
- Actual weight on study Days 7 (± 1 day), 14 (± 1 day), 21 (± 1 day), and 28 (± 1 day) of study drug administration
- Date, time, amount, and route of study drug dose
- All concomitant medications
- MAP
- All MAP values obtained 24 hours after the first dose of study drug regardless of administration route.
- 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:
- 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.
- For subsequent IV doses, the lowest valid MAP value should be recorded daily while on study drug. iii. If the administration route is enteral:
- 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.
- For subsequent enteral doses, the lowest valid MAP value should be recorded daily while on study drug.
- Respiratory assessment, weekly
- Laboratory evaluations, at least every other week
- Echocardiograms and cardiac catheterization reports, if performed per local standard of care
- Pharmacokinetic (PK) sampling (after Day 7)
- 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:
- Date, time, amount and route of study drug dose
- MAP (the lowest MAP value on last day of wean should be recorded).
- Respiratory assessment on last day of wean
- Echocardiogram and cardiac catheterization reports, if performed per local standard of care
- 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:
- Physical examination, including actual weight
- MAP (the lowest valid MAP value on follow-up Day 1, 14, 21, and 28 should be recorded).
- Respiratory assessment
- Laboratory evaluations
- 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.
- Echocardiograms and cardiac catheterization reports, if performed per local standard of care (during follow-up Days 1-28)
- 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:
- Physical examination, including actual weight
- Respiratory assessment
- 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.
- Global rank
- Discharge information A. Discharge or transfer B. Death C. Duration of hospitalization
- Record if treatment for retinopathy of prematurity (ROP) was required
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
- Model description
- Premature infants with severe BPD (inpatient in neonatal intensive care units) will be randomized in a dose escalating approach 3:1 (sildenafil: placebo) sequentially, into each of 3 cohorts. There will be approximately 40 randomized and dosed participants in each cohort for a total of up to 120 participants.
| Arm | Type | Receives |
|---|---|---|
| Cohort 1, sildenafil | Active comparator | Drug: SildenafilSildenafil (0.5 mg/kg IV or 1 mg/kg enteral) every 8 hours for 28 days |
| Cohort 1, placebo | Placebo comparator | Drug: PlaceboPlacebo (IV or enteral) every 8 hours for 28 days |
| Cohort 2, sildenafil | Active comparator | Drug: SildenafilSildenafil (1 mg/kg IV or 2 mg/kg enteral) every 8 hours for 28 days |
| Cohort 2, placebo | Placebo comparator | Drug: PlaceboPlacebo (IV or enteral) every 8 hours for 28 days |
| Cohort 3, sildenafil | Active comparator | Drug: SildenafilSildenafil (2 mg/kg IV or 4 mg/kg enteral) every 8 hours for 28 days |
| Cohort 3, placebo | Placebo comparator | Drug: PlaceboPlacebo (IV or enteral) every 8 hours for 28 days |
Who may qualify
- Ages
- Up to 29 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (14 listed)
- Documented informed consent from parent or guardian, prior to study procedures
- < 29 weeks gestational age at birth
- 32-44 weeks postmenstrual age
- Receiving respiratory support at enrollment:
- Criteria 3 and 4 define severe BPD for the purposes of this study
Key exclusion criteria (13 listed)
- Previous enrollment and dosing in this study, protocol number (NHLBI-2019-SIL), "Safety of Sildenafil in Premature Infants with Severe Bronchopulmonary Dysplasia (BPD)"
- Previous exposure to sildenafil within 7 days prior to randomization*
- Previous exposure to vasopressors within 24 hours prior to randomization*
- Previous exposure to inhaled nitric oxide within 24 hours prior to randomization*
- Previous exposure to milrinone within 24 hours prior to randomization*
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SildenafilAlso: RevatioSildenafil citrate injection or powder for suspension | Drug | Cohort 1, sildenafil, Cohort 2, sildenafil, Cohort 3, sildenafil |
| PlaceboAlso: Dextrose 5%dextrose 5% | Drug | Cohort 1, placebo, Cohort 2, placebo, Cohort 3, placebo |
Primary outcome
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.
5 secondary outcomes
Central Volume of Distribution (Vc) Population Pharmacokinetics (popPK)
Time frame: 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
Clearance Population Pharmacokinetics (popPK)
Time frame: 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
Peak Plasma Concentration Population Pharmacokinetics (popPK)
Time frame: Following the completion of 7 days (168 hours) of study drug administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 31475367Gonzalez D, Laughon MM, Smith PB, Ge S, Ambalavanan N, Atz A, Sokol GM, Hornik CD, Stewart D, Mundakel G, Poindexter BB, Gaedigk R, Mills M, Cohen-Wolkowiez M, Martz K, Hornik CP; Best Pharmaceuticals for Children Act - Pediatric Trials Network Steering Committee. Population pharmacokinetics of sildenafil in extremely premature infants. Br J Clin Pharmacol. 2019 Dec;85(12):2824-2837. doi: 10.1111/bcp.14111. Epub 2019 Dec 15.
- Background: PubMed 26348753Stoll BJ, Hansen NI, Bell EF, Walsh MC, Carlo WA, Shankaran S, Laptook AR, Sanchez PJ, Van Meurs KP, Wyckoff M, Das A, Hale EC, Ball MB, Newman NS, Schibler K, Poindexter BB, Kennedy KA, Cotten CM, Watterberg KL, D'Angio CT, DeMauro SB, Truog WE, Devaskar U, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Trends in Care Practices, Morbidity, and Mortality of Extremely Preterm Neonates, 1993-2012. JAMA. 2015 Sep 8;314(10):1039-51. doi: 10.1001/jama.2015.10244.
- Background: PubMed 11401896Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001 Jun;163(7):1723-9. doi: 10.1164/ajrccm.163.7.2011060. No abstract available.
- Background: PubMed 18055675Khemani E, McElhinney DB, Rhein L, Andrade O, Lacro RV, Thomas KC, Mullen MP. Pulmonary artery hypertension in formerly premature infants with bronchopulmonary dysplasia: clinical features and outcomes in the surfactant era. Pediatrics. 2007 Dec;120(6):1260-9. doi: 10.1542/peds.2007-0971.
- Background: PubMed 29880793Morrow CB, McGrath-Morrow SA, Collaco JM. Predictors of length of stay for initial hospitalization in infants with bronchopulmonary dysplasia. J Perinatol. 2018 Sep;38(9):1258-1265. doi: 10.1038/s41372-018-0142-7. Epub 2018 Jun 8.
- Background: PubMed 28383537Jackson W, Hornik CP, Messina JA, Guglielmo K, Watwe A, Delancy G, Valdez A, MacArthur T, Peter-Wohl S, Smith PB, Tolia VN, Laughon MM. In-hospital outcomes of premature infants with severe bronchopulmonary dysplasia. J Perinatol. 2017 Jul;37(7):853-856. doi: 10.1038/jp.2017.49. Epub 2017 Apr 6.
- Background: PubMed 29363502Poets CF, Lorenz L. Prevention of bronchopulmonary dysplasia in extremely low gestational age neonates: current evidence. Arch Dis Child Fetal Neonatal Ed. 2018 May;103(3):F285-F291. doi: 10.1136/archdischild-2017-314264. Epub 2018 Jan 23.
- Background: PubMed 10379020Tyson JE, Wright LL, Oh W, Kennedy KA, Mele L, Ehrenkranz RA, Stoll BJ, Lemons JA, Stevenson DK, Bauer CR, Korones SB, Fanaroff AA. Vitamin A supplementation for extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. N Engl J Med. 1999 Jun 24;340(25):1962-8. doi: 10.1056/NEJM199906243402505.
- Background: PubMed 16707748Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, Solimano A, Tin W; Caffeine for Apnea of Prematurity Trial Group. Caffeine therapy for apnea of prematurity. N Engl J Med. 2006 May 18;354(20):2112-21. doi: 10.1056/NEJMoa054065.
- Background: PubMed 24825456Doyle LW, Ehrenkranz RA, Halliday HL. Early (< 8 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants. Cochrane Database Syst Rev. 2014 May 13;(5):CD001146. doi: 10.1002/14651858.CD001146.pub4.
- Derived from this study: PubMed 42105936Jackson WM, Foote HP, Stephenson N, Kemp SM, Moore RT, Nitkin CR, Stewart D, Pryhuber GS, Berger JT, Shukla A, England A, Ford SM, Parton LA, Check JF, Hanna MH, Lagoski M, Krishnan R, Leeman KT, Vyas-Read S, Hudak ML, Katheria AC, Pillers DM, Ji J, Banfro F, Nelin LD, McCulloch M, Ahmad K, Laughon MM, Hornik CP; SILDI-SAFE Study Group. Safety of Sildenafil in Premature Infants with Severe Bronchopulmonary Dysplasia (SILDI-SAFE): A Randomized Controlled Trial. J Pediatr. 2026 Aug;295:115147. doi: 10.1016/j.jpeds.2026.115147. Epub 2026 May 7.
- Derived from this study: PubMed 33317479Schneider S, Bailey M, Spears T, Esther CR Jr, Laughon MM, Hornik CP, Jackson W. Safety of sildenafil in premature infants with severe bronchopulmonary dysplasia (SILDI-SAFE): a multicenter, randomized, placebo-controlled, sequential dose-escalating, double-masked, safety study. BMC Pediatr. 2020 Dec 14;20(1):559. doi: 10.1186/s12887-020-02453-7.
- Individual participant dataSharing planned: No. There is no plan to make IPD available to other researchers
Related trials for Bronchopulmonary Dysplasia of Newborn
Recruiting
Optimization of Saturation Targets And Resuscitation Trial (OptiSTART)
Premature Infants, Bronchopulmonary Dysplasia
Recruiting
Controlled Remote Monitoring and Optimization of Oxygen Therapy in Preterm Infants
BPD - Bronchopulmonary Dysplasia, Pulmonary Hypertension
Not yet recruitingPhase 1/2
Little Lungs Study
Invasive Mechanical Ventilation, Severe Respiratory Distress Syndrome
Not yet recruiting
Strap To Reduce Apnea in Preterm Infants: A Randomized Crossover Trial
Apnea of Prematurity, Intermittent Hypoxemia
Recruiting
Ventilator Pressure and Optimization of Compliance and Hemodynamics
Bronchopulmonary Dysplasia, Pulmonary Hypertension Due to Lung Diseases and Hypoxia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christoph Hornik, MD principal investigator
Duke UMC
Matt Laughon, MD principal investigator
UNC
25 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sildenafil in people with Bronchopulmonary Dysplasia of Newborn, run by Christoph Hornik at 25 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety Based Upon Number of Participants With Hypotension (time frame: 28 days post last dose of study drug, up to 9 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04447989, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2026.