Bronchopulmonary DysplasiaPhase 2SIL02NCT03142568
Safety of Sildenafil in Premature Infants
A Phase 2 study testing Sildenafil in people with Bronchopulmonary Dysplasia, run by University of North Carolina, Chapel Hill at 15 sites in 2 countries.
Trial summary
Describe the safety of sildenafil in premature infants at risk of bronchopulmonary dysplasia and determine preliminary effectiveness and pharmacokinetics (PK) of sildenafil. Funding Source - FDA Office of Orphan Products Development (OOPD). Read more about this study
- Who is it for?
- Ages 7 to 28 days
- Conditions the study is for
- Bronchopulmonary Dysplasia
- 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
- 109 participants
- Where
- 15 sitesin 2 countries
- Study dates
- 2 Apr 2018to 1 Mar 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 7 to 28 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Receiving positive airway pressure (nasal continuous airway pressure, nasal intermittent positive pressure ventilation, or nasal cannula flow > 1LPM) or mechanical ventilation (high frequency or conventional)
- <29 weeks gestational age at birth
- 7-28 (inclusive) days postnatal age at time of randomization
Who cannot join
- Currently receiving vasopressors
- Currently receiving inhaled nitric oxide
- Baseline mean arterial pressure < gestational age (in weeks) plus postnatal age (in weeks) within 2 hours of sildenafil administration
- 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
Trial locations and contacts
15 sites in 2 countries.
15 sites in 2 countries
United States14 sites
University of Illinois at Chicago
Chicago, Illinois, 60612
University of Mississippi Medical Center
Jackson, Mississippi, 39216
University of Florida College of Medicine Jacksonville-Wolfson Children's Hospital
Jacksonville, Florida, 32209
University of Florida Jacksonville Shands Medical Center
Jacksonville, Florida, 32209
Children's Hospital of Nevada at UMC
Las Vegas, Nevada, 89106
University of Kentucky
Lexington, Kentucky, 40356
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Monmouth Medical Center
Long Branch, New Jersey, 07740
Cohen Children's Medical Center of NY
New Hyde Park, New York, 11040
Ochsner Baptist Medical Center
New Orleans, Louisiana, 70115
University of Oklahoma
Oklahoma City, Oklahoma, 73104
WakeMed Health and Hospitals
Raleigh, North Carolina, 27610
Golisano Children's Hospital - University of Rochester Medical Center
Rochester, New York, 14642
Wesley Medical Center
Wichita, Kansas, 67214
About this study
Official title: Safety of Sildenafil in Premature Infants at Risk of Bronchopulmonary Dysplasia
Describe the safety of sildenafil in premature infants at risk of bronchopulmonary dysplasia and determine preliminary effectiveness and pharmacokinetics (PK) of sildenafil. Funding Source - FDA Office of Orphan Products Development (OOPD).
Read the detailed description
This will be a multi-center, randomized, placebo-controlled, sequential dose escalating, double masked, safety data study of sildenafil in premature infants.
This is a Phase II study design, premature infants (inpatient in neonatal intensive care units) will be randomized in a dose escalating approach 3:1 (sildenafil: placebo) into 3 cohorts with escalating doses of sildenafil. There will be 40 randomized and dosed participants in each cohort for a total of up to 120 participants. Cohort 1 sildenafil dose will be 0.125 mg/kg q 8 hours IV or 0.25 mg/kg q 8 hours enteral. Cohort 2 sildenafil dose will be 0.5 mg/kg q 8 hours IV or 1.0 mg/kg q 8 hours enteral. Cohort 3 sildenafil dose will be 1 mg/kg q 8 hours IV or 2 mg/kg q 8 hours enteral.
- Conditions
- Bronchopulmonary Dysplasia
- 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
Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo.
PlaceboOther
Also called sugar water
Infants randomized to the placebo group will receive the equivalent volume of dextrose 5% for IV use or enteral use (if receiving enteral study drug).
| Study group | Role | What they receive |
|---|---|---|
| Sildenafil cohort 1 | Experimental | Within cohort 1 infants will be randomized using a 3:1 scheme to receive sildenafil or placebo. Infants randomized to sildenafil will receive 0.125 mg/kg daily every 8 hours intravenously (IV), or 0.25 mg/kg daily every 8 hours enterally for 28 days. Receives: Drug: Sildenafil |
| Placebo cohort 1 | Placebo comparator | Infants randomized to the placebo treatment group will receive the equivalent of dextrose 5% (sugar water) to be administered IV or enteral use. Receives: Other: Placebo |
| Sildenafil cohort 2 | Experimental | Cohort 2 infants will receive sildenafil 0.5 mg/kg daily every 8 hours intravenously (IV) or 1 mg/kg daily every 8 hours enterally for 28 days. Receives: Drug: Sildenafil |
| Placebo cohort 2 | Placebo comparator | Infants randomized to the placebo treatment group will receive the equivalent of dextrose 5% (sugar water) to be administered IV or enteral use. Receives: Other: Placebo |
| Sildenafil cohort 3 | Experimental | Cohort 3 infants will receive sildenafil 1 mg/kg daily every 8 hours intravenously (IV) or 2 mg/kg daily every 8 hours enterally for 28 days. Receives: Drug: Sildenafil |
| Placebo cohort 3 | Placebo comparator | Infants randomized to the placebo treatment group will receive the equivalent of dextrose 5% (sugar water) to be administered IV or enteral use. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety as Determined by Adverse Event Experienced by Participants
Description of safety of sildenafil in premature infants and assessed by frequency and incidence of adverse events (AEs) and serious adverse events. Both non-serious and serious adverse events were collected from the time of informed consent through Day 14 after the last study intervention. Serious adverse events were additionally collected through 28 days after the last study intervention. Retinopathy of prematurity (ROP), whether serious or non-serious, was collected through hospital discharge or transfer; hospitalization duration varied based on clinical course, the longest duration was up to 575 days.
Measured: Nonserious AEs were collected through Day 14 post last intervention; SAEs through Day 28. Retinopathy of prematurity was assessed through discharge/transfer, up to 575 days after first treatment.
Secondary outcomes (6)
Volume of Distribution
Volume of distribution was estimated for participants receiving active study drug using a population pharmacokinetic model. Pharmacokinetic samples were collected after approximately 7 days on study drug at protocol-defined time points (0-15 minutes, 30-60 minutes, 1-2 hours, 2-3 hours, 3-4 hours, 4-5 hours, within 15 minutes prior to the next dose, and 16-24 hours after the last dose) through 28 days of treatment.
Measured: Pharmacokinetic samples were collected after any dose following completion of 7 days of study drug administration through Day 28 of study drug administration.
Clearance
Clearance was estimated for participants receiving active study drug using a population pharmacokinetic model. Pharmacokinetic samples were collected after approximately 7 days on study drug at protocol-defined time points (0-15 minutes, 30-60 minutes, 1-2 hours, 2-3 hours, 3-4 hours, 4-5 hours, within 15 minutes prior to the next dose, and 16-24 hours after the last dose) through 28 days of treatment.
Measured: Pharmacokinetic samples were collected after any dose following completion of 7 days of study drug administration through Day 28 of study drug administration.
Half-Life
Half-life was estimated for participants receiving active study drug using a population pharmacokinetic model. Pharmacokinetic samples were collected after approximately 7 days on study drug at protocol-defined time points (0-15 minutes, 30-60 minutes, 1-2 hours, 2-3 hours, 3-4 hours, 4-5 hours, within 15 minutes prior to the next dose, and 16-24 hours after the last dose) through 28 days of treatment.
Measured: Pharmacokinetic samples were collected after any dose following completion of 7 days of study drug administration through Day 28 of study drug administration.
Area Under the Curve (AUC)
Exposure, as measured by area under the plasma concentration-time curve (AUC), was estimated for participants receiving active study drug using a population pharmacokinetic model. Pharmacokinetic samples were collected after approximately 7 days on study drug at protocol-defined time points (0-15 minutes, 30-60 minutes, 1-2 hours, 2-3 hours, 3-4 hours, 4-5 hours, within 15 minutes prior to the next dose, and 16-24 hours after the last dose) through 28 days of treatment.
Measured: Pharmacokinetic samples were collected after any dose following completion of 7 days of study drug administration through Day 28 of study drug administration.
Peak Plasma Concentration
Maximum plasma concentration (Cmax) was estimated for participants receiving active study drug using a population pharmacokinetic model. Pharmacokinetic samples were collected after approximately 7 days on study drug at protocol-defined time points (0-15 minutes, 30-60 minutes, 1-2 hours, 2-3 hours, 3-4 hours, 4-5 hours, within 15 minutes prior to the next dose, and 16-24 hours after the last dose) through 28 days of treatment.
Measured: Pharmacokinetic samples were collected after any dose following completion of 7 days of study drug administration through Day 28 of study drug administration.
Change in Moderate-severe BPD or Death
Moderate-severe bronchopulmonary dysplasia (BPD) or death risk will be defined by the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network (NRN) BPD outcome estimator. https://neonatal.rti.org/. The outcome measure is a reduction in moderate-severe BPD or death risk from day 1 of study drug to end of study drug administration.
The BPD outcome estimator uses the following to calculate risk of BPD: Gestational age, Birth weight, Sex, Maternal Race/EthnicitylmPostnatal day, Ventilation type, Fraction of Inspired Oxygen
The NICHD NRN BPD estimator calculates the risk of BPD (none, mild, moderate, severe) or death by postnatal day, as a percentage. For this protocol, outcomes will be dichotomized as none-mild vs. moderate-severe-death.
Risk estimates will be recorded on days 7, 14, 21, and 28 of the study drug period, using the day closest to the participants postnatal age. For infants older than 28 days, the day 28 estimate will be applied.
Measured: From the first day of study drug administration to the end of study drug administration, up to 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2017
- Study start2 Apr 2018
- Primary completion1 Mar 2025
- Study completion1 Mar 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.
- Other trials for Bronchopulmonary DysplasiaStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- 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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 109 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Duke University, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), The Emmes Company, LLC
- Responsible party
- Sponsor
- Investigators
- Matthew M Laughon, MD, MPH, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03142568
- Sponsor's protocol ID
- 17-2436
- Other IDs
- 75N94022F00001, R01FD006099-01
- Acronym
- SIL02
- Status last verified
- Dec 2025
- First submitted
- 17 Apr 2017
- Last updated
- 30 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety of Sildenafil in Premature Infants at Risk of Bronchopulmonary Dysplasia
- ClinicalTrials.gov ID
- NCT03142568
- Acronym / sponsor ID
- SIL02 / 17-2436
- Conditions
- Bronchopulmonary Dysplasia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 109 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Duke University, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), The Emmes Company, LLC
- Study start
- 2 Apr 2018 (actual)
- Primary completion
- 1 Mar 2025 (actual)
- Study completion
- 1 Mar 2025 (actual)
- First posted
- 5 May 2017 (actual)
- Results
- Posted 11 Mar 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Describe the safety of sildenafil in premature infants at risk of bronchopulmonary dysplasia and determine preliminary effectiveness and pharmacokinetics (PK) of sildenafil. Funding Source - FDA Office of Orphan Products Development (OOPD).
Detailed description
This will be a multi-center, randomized, placebo-controlled, sequential dose escalating, double masked, safety data study of sildenafil in premature infants.
This is a Phase II study design, premature infants (inpatient in neonatal intensive care units) will be randomized in a dose escalating approach 3:1 (sildenafil: placebo) into 3 cohorts with escalating doses of sildenafil. There will be 40 randomized and dosed participants in each cohort for a total of up to 120 participants. Cohort 1 sildenafil dose will be 0.125 mg/kg q 8 hours IV or 0.25 mg/kg q 8 hours enteral. Cohort 2 sildenafil dose will be 0.5 mg/kg q 8 hours IV or 1.0 mg/kg q 8 hours enteral. Cohort 3 sildenafil dose will be 1 mg/kg q 8 hours IV or 2 mg/kg q 8 hours enteral.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Sildenafil cohort 1 | Experimental | Drug: SildenafilWithin cohort 1 infants will be randomized using a 3:1 scheme to receive sildenafil or placebo. Infants randomized to sildenafil will receive 0.125 mg/kg daily every 8 hours intravenously (IV), or 0.25 mg/kg daily every 8 hours enterally for 28 days. |
| Placebo cohort 1 | Placebo comparator | Other: PlaceboInfants randomized to the placebo treatment group will receive the equivalent of dextrose 5% (sugar water) to be administered IV or enteral use. |
| Sildenafil cohort 2 | Experimental | Drug: SildenafilCohort 2 infants will receive sildenafil 0.5 mg/kg daily every 8 hours intravenously (IV) or 1 mg/kg daily every 8 hours enterally for 28 days. |
| Placebo cohort 2 | Placebo comparator | Other: PlaceboInfants randomized to the placebo treatment group will receive the equivalent of dextrose 5% (sugar water) to be administered IV or enteral use. |
| Sildenafil cohort 3 | Experimental | Drug: SildenafilCohort 3 infants will receive sildenafil 1 mg/kg daily every 8 hours intravenously (IV) or 2 mg/kg daily every 8 hours enterally for 28 days. |
| Placebo cohort 3 | Placebo comparator | Other: PlaceboInfants randomized to the placebo treatment group will receive the equivalent of dextrose 5% (sugar water) to be administered IV or enteral use. |
Who may qualify
- Ages
- 7 to 28 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Receiving positive airway pressure (nasal continuous airway pressure, nasal intermittent positive pressure ventilation, or nasal cannula flow > 1LPM) or mechanical ventilation (high frequency or conventional)
- <29 weeks gestational age at birth
- 7-28 (inclusive) days postnatal age at time of randomization
Key exclusion criteria (7 listed)
- Currently receiving vasopressors
- Currently receiving inhaled nitric oxide
- Baseline mean arterial pressure < gestational age (in weeks) plus postnatal age (in weeks) within 2 hours of sildenafil administration
- Known allergy to sildenafil
- Known sickle cell disease
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: RevatioInfants will be randomized using a 3:1 scheme to receive sildenafil or placebo. | Drug | Sildenafil cohort 1, Sildenafil cohort 2, Sildenafil cohort 3 |
| PlaceboAlso: sugar waterInfants randomized to the placebo group will receive the equivalent volume of dextrose 5% for IV use or enteral use (if receiving enteral study drug). | Other | Placebo cohort 1, Placebo cohort 2, Placebo cohort 3 |
Primary outcome
Safety as Determined by Adverse Event Experienced by Participants
Time frame: Nonserious AEs were collected through Day 14 post last intervention; SAEs through Day 28. Retinopathy of prematurity was assessed through discharge/transfer, up to 575 days after first treatment.
Description of safety of sildenafil in premature infants and assessed by frequency and incidence of adverse events (AEs) and serious adverse events. Both non-serious and serious adverse events were collected from the time of informed consent through Day 14 after the last study intervention. Serious adverse events were additionally collected through 28 days after the last study intervention. Retinopathy of prematurity (ROP), whether serious or non-serious, was collected through hospital discharge or transfer; hospitalization duration varied based on clinical course, the longest duration was up to 575 days.
6 secondary outcomes
Volume of Distribution
Time frame: Pharmacokinetic samples were collected after any dose following completion of 7 days of study drug administration through Day 28 of study drug administration.
Clearance
Time frame: Pharmacokinetic samples were collected after any dose following completion of 7 days of study drug administration through Day 28 of study drug administration.
Half-Life
Time frame: Pharmacokinetic samples were collected after any dose following completion of 7 days of study drug administration through Day 28 of study drug administration.
Area Under the Curve (AUC)
Time frame: Pharmacokinetic samples were collected after any dose following completion of 7 days of study drug administration through Day 28 of study drug administration.
Peak Plasma Concentration
Time frame: Pharmacokinetic samples were collected after any dose following completion of 7 days of study drug administration through Day 28 of study drug administration.
Change in Moderate-severe BPD or Death
Time frame: From the first day of study drug administration to the end of study drug administration, up to 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Matthew M Laughon, MD, MPH principal investigator
University of North Carolina, Chapel Hill
15 sites in 2 countries: 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, run by University of North Carolina, Chapel Hill at 15 sites in 2 countries.
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 3 inclusion and 7 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 30 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States, Canada. 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 11 Mar 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 as Determined by Adverse Event Experienced by Participants (time frame: Nonserious AEs were collected through Day 14 post last intervention; SAEs through Day 28. Retinopathy of prematurity was assessed through discharge/transfer, up to 575 days after first treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Mar 2026.