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| ID | Type | Description | Link |
|---|---|---|---|
| 75N94022F00001 | Other Grant/Funding Number | NICHD | |
| R01FD006099-01 | U.S. FDA Grant/Contract | View source |
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| Name | Class |
|---|---|
| Duke University | OTHER |
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
| The Emmes Company, LLC | INDUSTRY |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
| 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. |
|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sildenafil | Drug | Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Matthew M Laughon, MD, MPH | University of North Carolina, Chapel Hill | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Arkansas for Medical Sciences | Little Rock | Arkansas | 72205 | United States | ||
| University of Florida College of Medicine Jacksonville-Wolfson Children's Hospital |
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In total, 109 individuals provided informed consent. Three were not randomized and therefore did not receive study intervention, 106 participants were consented and randomized to a study arm/group (started).
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| ID | Title | Description |
|---|---|---|
| FG000 | Sildenafil Cohort 1 | 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. Sildenafil: Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 3, 2023 | Dec 16, 2025 |
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|
| 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. |
|
|
| Placebo | Other | 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). |
|
|
| 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. | 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. | 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. | 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. | 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. | From the first day of study drug administration to the end of study drug administration, up to 28 days |
| Jacksonville |
| Florida |
| 32209 |
| United States |
| University of Florida Jacksonville Shands Medical Center | Jacksonville | Florida | 32209 | United States |
| University of Illinois at Chicago | Chicago | Illinois | 60612 | United States |
| Wesley Medical Center | Wichita | Kansas | 67214 | United States |
| University of Kentucky | Lexington | Kentucky | 40356 | United States |
| Ochsner Baptist Medical Center | New Orleans | Louisiana | 70115 | United States |
| University of Mississippi Medical Center | Jackson | Mississippi | 39216 | United States |
| Children's Hospital of Nevada at UMC | Las Vegas | Nevada | 89106 | United States |
| Monmouth Medical Center | Long Branch | New Jersey | 07740 | United States |
| Cohen Children's Medical Center of NY | New Hyde Park | New York | 11040 | United States |
| Golisano Children's Hospital - University of Rochester Medical Center | Rochester | New York | 14642 | United States |
| WakeMed Health and Hospitals | Raleigh | North Carolina | 27610 | United States |
| University of Oklahoma | Oklahoma City | Oklahoma | 73104 | United States |
| Health Sciences Centre Hospital | Winnipeg | Manitoba | R3A 1R9 | Canada |
| FG001 |
| Placebo Cohort 1 |
Infants randomized to the placebo treatment group will receive the equivalent of dextrose 5% (sugar water) to be administered IV or enteral use. Placebo: 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). |
| FG002 | Sildenafil Cohort 2 | 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. Sildenafil: Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo. |
| FG003 | Placebo Cohort 2 | Infants randomized to the placebo treatment group will receive the equivalent of dextrose 5% (sugar water) to be administered IV or enteral use. Placebo: 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). |
| FG004 | Sildenafil Cohort 3 | 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. Sildenafil: Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo. |
| FG005 | Placebo Cohort 3 | Infants randomized to the placebo treatment group will receive the equivalent of dextrose 5% (sugar water) to be administered IV or enteral use. Placebo: 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). |
| Received Intervention |
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| Pharmacokinetics Population | Participants who received active study drug and provided sufficient Pharmacokinetics samples to meet protocol criteria for pharmacokinetic analyses. |
|
| COMPLETED |
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| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Sildenafil Cohort 1 | 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. Sildenafil: Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo. |
| BG001 | Placebo Cohort 1 | Infants randomized to the placebo treatment group will receive the equivalent of dextrose 5% (sugar water) to be administered IV or enteral use. Placebo: 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). |
| BG002 | Sildenafil Cohort 2 | 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. Sildenafil: Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo. |
| BG003 | Placebo Cohort 2 | Infants randomized to the placebo treatment group will receive the equivalent of dextrose 5% (sugar water) to be administered IV or enteral use. Placebo: 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). |
| BG004 | Sildenafil Cohort 3 | 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. Sildenafil: Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo. |
| BG005 | Placebo Cohort 3 | Infants randomized to the placebo treatment group will receive the equivalent of dextrose 5% (sugar water) to be administered IV or enteral use. Placebo: 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). |
| BG006 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Gestational Age | Mean | Standard Deviation | Weeks |
| ||||||||||||||
| Age, Customized | Post Natal Age | Mean | Standard Deviation | Days |
| ||||||||||||||
| Sex: Female, Male | Count of Participants | Participants | No |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants | No |
| |||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants | No |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Outcome measures are presented by treatment group as defined in the protocol, which specifies 4 planned groups: 3 sildenafil groups and 1 combined placebo group. Participant flow, however, is shown by randomization cohort to provide transparency regarding enrollment and completion by cohort. Placebo participants were randomized separately within each cohort, displaying them individually in participant flow reflects the study design, while outcome analyses follow the protocol-defined grouping. | Posted | Number | Events | 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. |
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| Secondary | 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. | The number of participants analyzed for each pharmacokinetic outcome may differ from the overall number enrolled because only participants with valid data for that specific time point are included. Variations occur due to missed visits or assessments, early withdrawal, discontinuation, death, and/or missing data elements required to calculate volume of distribution. Pharmacokinetic outcomes only assessed in participants who received active study drug. | Posted | Median | Full Range | L/kg | Pharmacokinetic samples were collected after any dose following completion of 7 days of study drug administration through Day 28 of study drug administration. |
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| Secondary | 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. | The number of participants analyzed for each pharmacokinetic outcome may differ from the overall number enrolled because only participants with valid data for that specific time point are included. Variations occur due to missed visits or assessments, early withdrawal, discontinuation, death, and/or missing data elements required to calculate clearance. Pharmacokinetic outcomes only assessed in participants who received active study drug. | Posted | Median | Full Range | L/h/kg | Pharmacokinetic samples were collected after any dose following completion of 7 days of study drug administration through Day 28 of study drug administration. |
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| Secondary | 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. | The number of participants analyzed for each pharmacokinetic outcome may differ from the overall number enrolled because only participants with valid data for that specific time point are included. Variations occur due to missed visits or assessments, early withdrawal, discontinuation, death, and/or missing data elements required to calculate half-life. Pharmacokinetic outcomes only assessed in participants who received active study drug. | Posted | Median | Full Range | hours | Pharmacokinetic samples were collected after any dose following completion of 7 days of study drug administration through Day 28 of study drug administration. |
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| Secondary | 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. | The number of participants analyzed for each pharmacokinetic outcome may differ from the overall number enrolled because only participants with valid data for that specific time point are included. Variations occur due to missed visits or assessments, early withdrawal, discontinuation, death, and/or missing data elements required to calculate area under the curve. Pharmacokinetic outcomes only assessed in participants who received active study drug. | Posted | Median | Full Range | ng*h/mL | Pharmacokinetic samples were collected after any dose following completion of 7 days of study drug administration through Day 28 of study drug administration. |
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| Secondary | 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. | The number of participants analyzed for each pharmacokinetic outcome may differ from the overall number enrolled because only participants with valid data for that specific time point are included. Variations occur due to missed visits or assessments, early withdrawal, discontinuation, death, and/or missing data elements required to calculate peak plasma concentration. Pharmacokinetic outcomes only assessed in participants who received active study drug. | Posted | Median | Full Range | ng/mL | Pharmacokinetic samples were collected after any dose following completion of 7 days of study drug administration through Day 28 of study drug administration. |
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| Secondary | 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. | The number of participants analyzed at each study week may differ from the overall number enrolled because only participants with valid data for that specific time point are included. Variations occur due to missed visits, early termination, and/or missing data elements. Participants in Sildenafil Cohort 1 did not undergo a weaning period due to the low sildenafil doses administered and the minimal risk of rebound effects. No data were collected or analyzed for this outcome in Cohort 1. | Posted | Mean | Standard Deviation | Percent probability of risk BPD or death | From the first day of study drug administration to the end of study drug administration, up to 28 days |
|
Non-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.
Safety events are presented by treatment group as defined in the protocol, which specifies 4 planned groups: 3 sildenafil groups and 1 combined placebo group. Participant flow, however, is shown by randomization cohort to provide transparency regarding enrollment and completion by cohort. Placebo participants were randomized separately within each cohort, displaying them individually in participant flow reflects the study design, while safety analyses follow the protocol-defined grouping.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Sildenafil Cohort 1 | 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. | 1 | 30 | 3 | 30 | 27 | 30 |
| EG001 | Sildenafil Cohort 2 | 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. | 1 | 30 | 8 | 30 | 27 | 30 |
| EG002 | Sildenafil Cohort 3 | 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. | 2 | 16 | 2 | 16 | 14 | 16 |
| EG003 | Placebo Total | Infants randomized to the placebo treatment group will receive the equivalent of dextrose 5% (sugar water) to be administered IV or enteral use. | 1 | 26 | 2 | 26 | 21 | 26 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Retinopathy of prematurity | Eye disorders | Systematic Assessment |
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| Necrotising colitis | Gastrointestinal disorders | Systematic Assessment |
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| Group B streptococcus neonatal sepsis | Infections and infestations | Systematic Assessment |
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| Metapneumovirus infection | Infections and infestations | Systematic Assessment |
| ||
| Pneumonia | Infections and infestations | Systematic Assessment |
| ||
| Pneumonia cytomegaloviral | Infections and infestations | Systematic Assessment |
| ||
| Serratia sepsis | Infections and infestations | Systematic Assessment |
| ||
| Seizure | Nervous system disorders | Systematic Assessment |
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| Apnoea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Bronchopulmonary dysplasia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Hypotension | Vascular disorders | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | Systematic Assessment |
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| Anaemia neonatal | Blood and lymphatic system disorders | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Bradycardia | Cardiac disorders | Systematic Assessment |
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| Bradycardia neonatal | Cardiac disorders | Systematic Assessment |
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| Right ventricular hypertension | Cardiac disorders | Systematic Assessment |
| ||
| Tachycardia | Cardiac disorders | Systematic Assessment |
| ||
| Hydrocele | Congenital, familial and genetic disorders | Systematic Assessment |
| ||
| Left-to-right cardiac shunt | Congenital, familial and genetic disorders | Systematic Assessment |
| ||
| Patent ductus arteriosus | Congenital, familial and genetic disorders | Systematic Assessment |
| ||
| Ventricular septal defect | Congenital, familial and genetic disorders | Systematic Assessment |
| ||
| Otorrhoea | Ear and labyrinth disorders | Systematic Assessment |
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| Adrenal insufficiency | Endocrine disorders | Systematic Assessment |
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| Adrenocorticotropic hormone deficiency | Endocrine disorders | Systematic Assessment |
| ||
| Retinopathy of prematurity | Eye disorders | Systematic Assessment |
| ||
| Abdominal distension | Gastrointestinal disorders | Systematic Assessment |
| ||
| Constipation | Gastrointestinal disorders | Systematic Assessment |
| ||
| Gastrointestinal haemorrhage | Gastrointestinal disorders | Systematic Assessment |
| ||
| Gastrooesophageal reflux disease | Gastrointestinal disorders | Systematic Assessment |
| ||
| Inguinal hernia | Gastrointestinal disorders | Systematic Assessment |
| ||
| Necrotising colitis | Gastrointestinal disorders | Systematic Assessment |
| ||
| Umbilical hernia | Gastrointestinal disorders | Systematic Assessment |
| ||
| Injection site extravasation | General disorders | Systematic Assessment |
| ||
| Bacterial disease carrier | Infections and infestations | Systematic Assessment |
| ||
| Candida infection | Infections and infestations | Systematic Assessment |
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| Conjunctivitis | Infections and infestations | Systematic Assessment |
| ||
| Ear infection | Infections and infestations | Systematic Assessment |
| ||
| Enterobacter pneumonia | Infections and infestations | Systematic Assessment |
| ||
| Fungal skin infection | Infections and infestations | Systematic Assessment |
| ||
| Group B streptococcus neonatal sepsis | Infections and infestations | Systematic Assessment |
| ||
| Klebsiella infection | Infections and infestations | Systematic Assessment |
| ||
| Metapneumovirus infection | Infections and infestations | Systematic Assessment |
| ||
| Otitis media | Infections and infestations | Systematic Assessment |
| ||
| Pneumonia | Infections and infestations | Systematic Assessment |
| ||
| Pneumonia cytomegaloviral | Infections and infestations | Systematic Assessment |
| ||
| Pneumonia klebsiella | Infections and infestations | Systematic Assessment |
| ||
| Sepsis | Infections and infestations | Systematic Assessment |
| ||
| Serratia sepsis | Infections and infestations | Systematic Assessment |
| ||
| Staphylococcal infection | Infections and infestations | Systematic Assessment |
| ||
| Staphylococcal sepsis | Infections and infestations | Systematic Assessment |
| ||
| Tracheitis | Infections and infestations | Systematic Assessment |
| ||
| Urinary tract infection | Infections and infestations | Systematic Assessment |
| ||
| Urinary tract infection neonatal | Infections and infestations | Systematic Assessment |
| ||
| Skin abrasion | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Blood alkaline phosphatase increased | Investigations | Systematic Assessment |
| ||
| Blood phosphorus increased | Investigations | Systematic Assessment |
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| Cardiac murmur | Investigations | Systematic Assessment |
| ||
| Electrocardiogram T wave abnormal | Investigations | Systematic Assessment |
| ||
| Fecal occult blood positive | Investigations | Systematic Assessment |
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| Oxygen consumption increased | Investigations | Systematic Assessment |
| ||
| Carnitine deficiency | Metabolism and nutrition disorders | Systematic Assessment |
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| Feeding disorder | Metabolism and nutrition disorders | Systematic Assessment |
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| Feeding intolerance | Metabolism and nutrition disorders | Systematic Assessment |
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| Hyperkalaemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Hypernatraemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Hypoalbuminaemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Hypocalcaemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Hypochloraemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Hypoglycaemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Hyponatraemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Hypophosphataemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Malnutrition | Metabolism and nutrition disorders | Systematic Assessment |
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| Metabolic acidosis | Metabolism and nutrition disorders | Systematic Assessment |
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| Vitamin D deficiency | Metabolism and nutrition disorders | Systematic Assessment |
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| Osteopenia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Haemangioma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| Encephalomalacia | Nervous system disorders | Systematic Assessment |
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| Intraventricular haemorrhage neonatal | Nervous system disorders | Systematic Assessment |
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| Periventricular leukomalacia | Nervous system disorders | Systematic Assessment |
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| Posthaemorrhagic hydrocephalus | Nervous system disorders | Systematic Assessment |
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| Seizure | Nervous system disorders | Systematic Assessment |
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| Hydronephrosis | Renal and urinary disorders | Systematic Assessment |
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| Nephrocalcinosis | Renal and urinary disorders | Systematic Assessment |
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| Renal impairment | Renal and urinary disorders | Systematic Assessment |
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| Erection increased | Reproductive system and breast disorders | Systematic Assessment |
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| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Apnoea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Bronchial hyperreactivity | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Bronchopulmonary dysplasia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Chronic respiratory disease | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Infantile apnoea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Respiratory distress | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Respiratory failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Stridor | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Dermatitis diaper | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Skin disorder | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Skin irritation | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Hypotension | Vascular disorders | Systematic Assessment |
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Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Talaya McCright-Gill | Duke University | 321-566-3091 | talaya.mccright-gill@duke.edu |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 25, 2025 | Dec 17, 2025 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Nov 6, 2023 | Dec 9, 2025 | ICF_002.pdf |
Not provided
| ID | Term |
|---|---|
| D001997 | Bronchopulmonary Dysplasia |
| ID | Term |
|---|---|
| D055397 | Ventilator-Induced Lung Injury |
| D055370 | Lung Injury |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D007235 | Infant, Premature, Diseases |
| D007232 | Infant, Newborn, Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
Not provided
Not provided
| ID | Term |
|---|---|
| D000068677 | Sildenafil Citrate |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
Not provided
Not provided
| Male |
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| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
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| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
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.
Sildenafil: Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo.
| OG002 | Sildenafil Cohort 3 | 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. Sildenafil: Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo. |
|
|
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.
Sildenafil: Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo.
| OG002 | Sildenafil Cohort 3 | 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. Sildenafil: Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo. |
|
|
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.
Sildenafil: Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo.
| OG002 | Sildenafil Cohort 3 | 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. Sildenafil: Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo. |
|
|
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. Sildenafil: Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo. |
| OG002 | Sildenafil Cohort 3 | 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. Sildenafil: Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo. |
|
|
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. Sildenafil: Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo. |
| OG002 | Sildenafil Cohort 3 | 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. Sildenafil: Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo. |
|
|
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.
Sildenafil: Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo.
| OG001 | Sildenafil Cohort 2 | 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. Sildenafil: Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo. |
| OG002 | Sildenafil Cohort 3 | 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. Sildenafil: Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo. |
| OG003 | Placebo Total | Infants randomized to the placebo treatment group will receive the equivalent of dextrose 5% (sugar water) to be administered IV or enteral use. Placebo: 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). |
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