Trial Outcomes & Findings for Safety of Sildenafil in Premature Infants With Severe Bronchopulmonary Dysplasia (NCT NCT04447989)
NCT ID: NCT04447989
Last Updated: 2026-01-26
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
125 participants
Primary outcome timeframe
28 days post last dose of study drug, up to 9 weeks
Results posted on
2026-01-26
Participant Flow
Participant milestones
| Measure |
Cohort 1, Sildenafil
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-28.
|
Cohort 2, Sildenafil
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-4, 0.75 mg/kg IV or 1.5 mg/kg enteral on study days 5-6, 1 mg/kg IV or 2 mg/kg enteral on study days 7-28.
A weaning schedule was used following the last study dose on Day 28 or if the patient was withdrawn from the study and escalated to a dose \> 0.5 mg/kg IV or 1 mg/kg enteral. Whether IV or enteral, the weaning schedule was 75% of the last study dose on weaning days 1-2, 50% of the last study dose on weaning days 3-4, 25% of the last study dose on weaning days 5-6, and the weaning schedule was discontinued on weaning day 7.
|
Cohort 3, Sildenafil
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-4, 0.75 mg/kg IV or 1.5 mg/kg enteral on study days 5-6, 1 mg/kg IV or 2 mg/kg enteral on study days 7-8, 1.25 mg/kg IV or 2.5 mg/kg enteral on study days 9-10, 1.5 mg/kg IV or 3 mg/kg enteral on study days 11-12, 1.75 mg/kg IV or 3.5 mg/kg enteral on study days 13-14, 2 mg/kg IV or 4 mg/kg enteral on study days 15-28.
A weaning schedule was used following the last study dose on Day 28 or if the patient was withdrawn from the study and escalated to a dose \> 0.5 mg/kg IV or 1 mg/kg enteral. Whether IV or enteral, the weaning schedule was 75% of the last study dose on weaning days 1-2, 50% of the last study dose on weaning days 3-4, 25% of the last study dose on weaning days 5-6, and the weaning schedule was discontinued on weaning day 7.
|
Placebo
Placebo (IV or enteral) every 8 hours for 28 days
Placebo: dextrose 5%
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
32
|
30
|
32
|
31
|
|
Overall Study
COMPLETED
|
31
|
27
|
31
|
26
|
|
Overall Study
NOT COMPLETED
|
1
|
3
|
1
|
5
|
Reasons for withdrawal
| Measure |
Cohort 1, Sildenafil
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-28.
|
Cohort 2, Sildenafil
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-4, 0.75 mg/kg IV or 1.5 mg/kg enteral on study days 5-6, 1 mg/kg IV or 2 mg/kg enteral on study days 7-28.
A weaning schedule was used following the last study dose on Day 28 or if the patient was withdrawn from the study and escalated to a dose \> 0.5 mg/kg IV or 1 mg/kg enteral. Whether IV or enteral, the weaning schedule was 75% of the last study dose on weaning days 1-2, 50% of the last study dose on weaning days 3-4, 25% of the last study dose on weaning days 5-6, and the weaning schedule was discontinued on weaning day 7.
|
Cohort 3, Sildenafil
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-4, 0.75 mg/kg IV or 1.5 mg/kg enteral on study days 5-6, 1 mg/kg IV or 2 mg/kg enteral on study days 7-8, 1.25 mg/kg IV or 2.5 mg/kg enteral on study days 9-10, 1.5 mg/kg IV or 3 mg/kg enteral on study days 11-12, 1.75 mg/kg IV or 3.5 mg/kg enteral on study days 13-14, 2 mg/kg IV or 4 mg/kg enteral on study days 15-28.
A weaning schedule was used following the last study dose on Day 28 or if the patient was withdrawn from the study and escalated to a dose \> 0.5 mg/kg IV or 1 mg/kg enteral. Whether IV or enteral, the weaning schedule was 75% of the last study dose on weaning days 1-2, 50% of the last study dose on weaning days 3-4, 25% of the last study dose on weaning days 5-6, and the weaning schedule was discontinued on weaning day 7.
|
Placebo
Placebo (IV or enteral) every 8 hours for 28 days
Placebo: dextrose 5%
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
0
|
0
|
|
Overall Study
Physician Decision
|
0
|
0
|
0
|
1
|
|
Overall Study
Transfer
|
0
|
1
|
0
|
0
|
|
Overall Study
Discharge
|
0
|
1
|
1
|
3
|
|
Overall Study
Ineligibility
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Safety of Sildenafil in Premature Infants With Severe Bronchopulmonary Dysplasia
Baseline characteristics by cohort
| Measure |
Cohort 1, Sildenafil
n=32 Participants
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-28.
|
Cohort 2, Sildenafil
n=29 Participants
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-4, 0.75 mg/kg IV or 1.5 mg/kg enteral on study days 5-6, 1 mg/kg IV or 2 mg/kg enteral on study days 7-28.
A weaning schedule was used following the last study dose on Day 28 or if the patient was withdrawn from the study and escalated to a dose \> 0.5 mg/kg IV or 1 mg/kg enteral. Whether IV or enteral, the weaning schedule was 75% of the last study dose on weaning days 1-2, 50% of the last study dose on weaning days 3-4, 25% of the last study dose on weaning days 5-6, and the weaning schedule was discontinued on weaning day 7.
|
Cohort 3, Sildenafil
n=32 Participants
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-4, 0.75 mg/kg IV or 1.5 mg/kg enteral on study days 5-6, 1 mg/kg IV or 2 mg/kg enteral on study days 7-8, 1.25 mg/kg IV or 2.5 mg/kg enteral on study days 9-10, 1.5 mg/kg IV or 3 mg/kg enteral on study days 11-12, 1.75 mg/kg IV or 3.5 mg/kg enteral on study days 13-14, 2 mg/kg IV or 4 mg/kg enteral on study days 15-28.
A weaning schedule was used following the last study dose on Day 28 or if the patient was withdrawn from the study and escalated to a dose \> 0.5 mg/kg IV or 1 mg/kg enteral. Whether IV or enteral, the weaning schedule was 75% of the last study dose on weaning days 1-2, 50% of the last study dose on weaning days 3-4, 25% of the last study dose on weaning days 5-6, and the weaning schedule was discontinued on weaning day 7.
|
Placebo
n=31 Participants
Placebo (IV or enteral) every 8 hours for 28 days
Placebo: dextrose 5%
|
Total
n=124 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=41 Participants
|
1 Participants
n=1581 Participants
|
3 Participants
n=4626 Participants
|
3 Participants
n=72 Participants
|
9 Participants
|
|
Region of Enrollment
United States
|
32 Participants
n=41 Participants
|
29 Participants
n=1581 Participants
|
32 Participants
n=4626 Participants
|
31 Participants
n=72 Participants
|
124 Participants
|
|
Age, Customized
Gestational age
|
25.16 weeks
STANDARD_DEVIATION 1.46 • n=41 Participants
|
25.49 weeks
STANDARD_DEVIATION 1.70 • n=1581 Participants
|
25.40 weeks
STANDARD_DEVIATION 1.59 • n=4626 Participants
|
25.45 weeks
STANDARD_DEVIATION 1.76 • n=72 Participants
|
25.37 weeks
STANDARD_DEVIATION 1.61
|
|
Age, Customized
Postnatal age
|
13.21 weeks
STANDARD_DEVIATION 3.44 • n=41 Participants
|
12.44 weeks
STANDARD_DEVIATION 3.12 • n=1581 Participants
|
11.96 weeks
STANDARD_DEVIATION 3.54 • n=4626 Participants
|
12.48 weeks
STANDARD_DEVIATION 3.43 • n=72 Participants
|
12.53 weeks
STANDARD_DEVIATION 3.38
|
|
Age, Customized
Post-menstrual age
|
38.37 weeks
STANDARD_DEVIATION 2.84 • n=41 Participants
|
37.94 weeks
STANDARD_DEVIATION 3.19 • n=1581 Participants
|
37.37 weeks
STANDARD_DEVIATION 2.73 • n=4626 Participants
|
37.94 weeks
STANDARD_DEVIATION 3.27 • n=72 Participants
|
37.90 weeks
STANDARD_DEVIATION 3.00
|
|
Sex: Female, Male
Female
|
17 Participants
n=41 Participants
|
17 Participants
n=1581 Participants
|
16 Participants
n=4626 Participants
|
9 Participants
n=72 Participants
|
59 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=41 Participants
|
12 Participants
n=1581 Participants
|
16 Participants
n=4626 Participants
|
22 Participants
n=72 Participants
|
65 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=41 Participants
|
0 Participants
n=1581 Participants
|
2 Participants
n=4626 Participants
|
1 Participants
n=72 Participants
|
5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
28 Participants
n=41 Participants
|
28 Participants
n=1581 Participants
|
27 Participants
n=4626 Participants
|
27 Participants
n=72 Participants
|
110 Participants
|
PRIMARY outcome
Timeframe: 28 days post last dose of study drug, up to 9 weeksPopulation: Safety population
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.
Outcome measures
| Measure |
Cohort 1, Sildenafil
n=31 Participants
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-28
|
Cohort 2, Sildenafil
n=29 Participants
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-4, 0.75 mg/kg IV or 1.5 mg/kg enteral on study days 5-6, 1 mg/kg IV or 2 mg/kg enteral on study days 7-28.
A weaning schedule was used following the last study dose on Day 28 or if the patient was withdrawn from the study and escalated to a dose \> 0.5 mg/kg IV or 1 mg/kg enteral. Whether IV or enteral, the weaning schedule was 75% of the last study dose on weaning days 1-2, 50% of the last study dose on weaning days 3-4, 25% of the last study dose on weaning days 5-6, and the weaning schedule was discontinued on weaning day 7.
|
Cohort 3, Sildenafil
n=32 Participants
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-4, 0.75 mg/kg IV or 1.5 mg/kg enteral on study days 5-6, 1 mg/kg IV or 2 mg/kg enteral on study days 7-8, 1.25 mg/kg IV or 2.5 mg/kg enteral on study days 9-10, 1.5 mg/kg IV or 3 mg/kg enteral on study days 11-12, 1.75 mg/kg IV or 3.5 mg/kg enteral on study days 13-14, 2 mg/kg IV or 4 mg/kg enteral on study days 15-28.
A weaning schedule was used following the last study dose on Day 28 or if the patient was withdrawn from the study and escalated to a dose \> 0.5 mg/kg IV or 1 mg/kg enteral. Whether IV or enteral, the weaning schedule was 75% of the last study dose on weaning days 1-2, 50% of the last study dose on weaning days 3-4, 25% of the last study dose on weaning days 5-6, and the weaning schedule was discontinued on weaning day 7.
|
Placebo
n=30 Participants
Placebo (IV or enteral) every 8 hours for 28 days
Placebo: dextrose 5%
|
|---|---|---|---|---|
|
Safety Based Upon Number of Participants With Hypotension
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Following the completion of 7 days (168 hours) of study drug administrationPopulation: Population Pharmacokinetics (popPK) analysis does not involve separating PK parameters by dose group. All samples across all dose groups are analyzed together.
Outcome measures
| Measure |
Cohort 1, Sildenafil
n=85 Participants
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-28
|
Cohort 2, Sildenafil
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-4, 0.75 mg/kg IV or 1.5 mg/kg enteral on study days 5-6, 1 mg/kg IV or 2 mg/kg enteral on study days 7-28.
A weaning schedule was used following the last study dose on Day 28 or if the patient was withdrawn from the study and escalated to a dose \> 0.5 mg/kg IV or 1 mg/kg enteral. Whether IV or enteral, the weaning schedule was 75% of the last study dose on weaning days 1-2, 50% of the last study dose on weaning days 3-4, 25% of the last study dose on weaning days 5-6, and the weaning schedule was discontinued on weaning day 7.
|
Cohort 3, Sildenafil
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-4, 0.75 mg/kg IV or 1.5 mg/kg enteral on study days 5-6, 1 mg/kg IV or 2 mg/kg enteral on study days 7-8, 1.25 mg/kg IV or 2.5 mg/kg enteral on study days 9-10, 1.5 mg/kg IV or 3 mg/kg enteral on study days 11-12, 1.75 mg/kg IV or 3.5 mg/kg enteral on study days 13-14, 2 mg/kg IV or 4 mg/kg enteral on study days 15-28.
A weaning schedule was used following the last study dose on Day 28 or if the patient was withdrawn from the study and escalated to a dose \> 0.5 mg/kg IV or 1 mg/kg enteral. Whether IV or enteral, the weaning schedule was 75% of the last study dose on weaning days 1-2, 50% of the last study dose on weaning days 3-4, 25% of the last study dose on weaning days 5-6, and the weaning schedule was discontinued on weaning day 7.
|
Placebo
Placebo (IV or enteral) every 8 hours for 28 days
Placebo: dextrose 5%
|
|---|---|---|---|---|
|
Central Volume of Distribution (Vc) Population Pharmacokinetics (popPK)
|
3.86 L
Interval 1.28 to 11.07
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Following the completion of 7 days (168 hours) of study drug administrationPopulation: Population Pharmacokinetics (popPK) analysis does not involve separating PK parameters by dose group. All samples across all dose groups are analyzed together.
Outcome measures
| Measure |
Cohort 1, Sildenafil
n=85 Participants
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-28
|
Cohort 2, Sildenafil
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-4, 0.75 mg/kg IV or 1.5 mg/kg enteral on study days 5-6, 1 mg/kg IV or 2 mg/kg enteral on study days 7-28.
A weaning schedule was used following the last study dose on Day 28 or if the patient was withdrawn from the study and escalated to a dose \> 0.5 mg/kg IV or 1 mg/kg enteral. Whether IV or enteral, the weaning schedule was 75% of the last study dose on weaning days 1-2, 50% of the last study dose on weaning days 3-4, 25% of the last study dose on weaning days 5-6, and the weaning schedule was discontinued on weaning day 7.
|
Cohort 3, Sildenafil
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-4, 0.75 mg/kg IV or 1.5 mg/kg enteral on study days 5-6, 1 mg/kg IV or 2 mg/kg enteral on study days 7-8, 1.25 mg/kg IV or 2.5 mg/kg enteral on study days 9-10, 1.5 mg/kg IV or 3 mg/kg enteral on study days 11-12, 1.75 mg/kg IV or 3.5 mg/kg enteral on study days 13-14, 2 mg/kg IV or 4 mg/kg enteral on study days 15-28.
A weaning schedule was used following the last study dose on Day 28 or if the patient was withdrawn from the study and escalated to a dose \> 0.5 mg/kg IV or 1 mg/kg enteral. Whether IV or enteral, the weaning schedule was 75% of the last study dose on weaning days 1-2, 50% of the last study dose on weaning days 3-4, 25% of the last study dose on weaning days 5-6, and the weaning schedule was discontinued on weaning day 7.
|
Placebo
Placebo (IV or enteral) every 8 hours for 28 days
Placebo: dextrose 5%
|
|---|---|---|---|---|
|
Peripheral Volume of Distribution (Vp) Population Pharmacokinetics (popPK)
|
4.49 L
Interval 2.87 to 6.66
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Following the completion of 7 days (168 hours) of study drug administrationPopulation: Population Pharmacokinetics (popPK) analysis does not involve separating PK parameters by dose group. All samples across all dose groups are analyzed together.
Outcome measures
| Measure |
Cohort 1, Sildenafil
n=85 Participants
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-28
|
Cohort 2, Sildenafil
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-4, 0.75 mg/kg IV or 1.5 mg/kg enteral on study days 5-6, 1 mg/kg IV or 2 mg/kg enteral on study days 7-28.
A weaning schedule was used following the last study dose on Day 28 or if the patient was withdrawn from the study and escalated to a dose \> 0.5 mg/kg IV or 1 mg/kg enteral. Whether IV or enteral, the weaning schedule was 75% of the last study dose on weaning days 1-2, 50% of the last study dose on weaning days 3-4, 25% of the last study dose on weaning days 5-6, and the weaning schedule was discontinued on weaning day 7.
|
Cohort 3, Sildenafil
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-4, 0.75 mg/kg IV or 1.5 mg/kg enteral on study days 5-6, 1 mg/kg IV or 2 mg/kg enteral on study days 7-8, 1.25 mg/kg IV or 2.5 mg/kg enteral on study days 9-10, 1.5 mg/kg IV or 3 mg/kg enteral on study days 11-12, 1.75 mg/kg IV or 3.5 mg/kg enteral on study days 13-14, 2 mg/kg IV or 4 mg/kg enteral on study days 15-28.
A weaning schedule was used following the last study dose on Day 28 or if the patient was withdrawn from the study and escalated to a dose \> 0.5 mg/kg IV or 1 mg/kg enteral. Whether IV or enteral, the weaning schedule was 75% of the last study dose on weaning days 1-2, 50% of the last study dose on weaning days 3-4, 25% of the last study dose on weaning days 5-6, and the weaning schedule was discontinued on weaning day 7.
|
Placebo
Placebo (IV or enteral) every 8 hours for 28 days
Placebo: dextrose 5%
|
|---|---|---|---|---|
|
Clearance Population Pharmacokinetics (popPK)
|
2.69 L/h
Interval 1.0 to 7.94
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Following the completion of 7 days (168 hours) of study drug administrationPopulation: Population Pharmacokinetics (popPK) analysis does not involve separating PK parameters by dose group. All samples across all dose groups are analyzed together.
Outcome measures
| Measure |
Cohort 1, Sildenafil
n=85 Participants
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-28
|
Cohort 2, Sildenafil
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-4, 0.75 mg/kg IV or 1.5 mg/kg enteral on study days 5-6, 1 mg/kg IV or 2 mg/kg enteral on study days 7-28.
A weaning schedule was used following the last study dose on Day 28 or if the patient was withdrawn from the study and escalated to a dose \> 0.5 mg/kg IV or 1 mg/kg enteral. Whether IV or enteral, the weaning schedule was 75% of the last study dose on weaning days 1-2, 50% of the last study dose on weaning days 3-4, 25% of the last study dose on weaning days 5-6, and the weaning schedule was discontinued on weaning day 7.
|
Cohort 3, Sildenafil
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-4, 0.75 mg/kg IV or 1.5 mg/kg enteral on study days 5-6, 1 mg/kg IV or 2 mg/kg enteral on study days 7-8, 1.25 mg/kg IV or 2.5 mg/kg enteral on study days 9-10, 1.5 mg/kg IV or 3 mg/kg enteral on study days 11-12, 1.75 mg/kg IV or 3.5 mg/kg enteral on study days 13-14, 2 mg/kg IV or 4 mg/kg enteral on study days 15-28.
A weaning schedule was used following the last study dose on Day 28 or if the patient was withdrawn from the study and escalated to a dose \> 0.5 mg/kg IV or 1 mg/kg enteral. Whether IV or enteral, the weaning schedule was 75% of the last study dose on weaning days 1-2, 50% of the last study dose on weaning days 3-4, 25% of the last study dose on weaning days 5-6, and the weaning schedule was discontinued on weaning day 7.
|
Placebo
Placebo (IV or enteral) every 8 hours for 28 days
Placebo: dextrose 5%
|
|---|---|---|---|---|
|
Half-life Population Pharmacokinetics (popPK)
|
8.79 hours
Interval 8.0 to 9.42
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Following the completion of 7 days (168 hours) of study drug administrationPopulation: Population Pharmacokinetics (popPK) analysis does not involve separating PK parameters by dose group. All samples across all dose groups are analyzed together.
Outcome measures
| Measure |
Cohort 1, Sildenafil
n=85 Participants
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-28
|
Cohort 2, Sildenafil
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-4, 0.75 mg/kg IV or 1.5 mg/kg enteral on study days 5-6, 1 mg/kg IV or 2 mg/kg enteral on study days 7-28.
A weaning schedule was used following the last study dose on Day 28 or if the patient was withdrawn from the study and escalated to a dose \> 0.5 mg/kg IV or 1 mg/kg enteral. Whether IV or enteral, the weaning schedule was 75% of the last study dose on weaning days 1-2, 50% of the last study dose on weaning days 3-4, 25% of the last study dose on weaning days 5-6, and the weaning schedule was discontinued on weaning day 7.
|
Cohort 3, Sildenafil
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-4, 0.75 mg/kg IV or 1.5 mg/kg enteral on study days 5-6, 1 mg/kg IV or 2 mg/kg enteral on study days 7-8, 1.25 mg/kg IV or 2.5 mg/kg enteral on study days 9-10, 1.5 mg/kg IV or 3 mg/kg enteral on study days 11-12, 1.75 mg/kg IV or 3.5 mg/kg enteral on study days 13-14, 2 mg/kg IV or 4 mg/kg enteral on study days 15-28.
A weaning schedule was used following the last study dose on Day 28 or if the patient was withdrawn from the study and escalated to a dose \> 0.5 mg/kg IV or 1 mg/kg enteral. Whether IV or enteral, the weaning schedule was 75% of the last study dose on weaning days 1-2, 50% of the last study dose on weaning days 3-4, 25% of the last study dose on weaning days 5-6, and the weaning schedule was discontinued on weaning day 7.
|
Placebo
Placebo (IV or enteral) every 8 hours for 28 days
Placebo: dextrose 5%
|
|---|---|---|---|---|
|
Peak Plasma Concentration Population Pharmacokinetics (popPK)
|
130.5 ng/mL
Interval 70.9 to 256.0
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 28 days post last dose of study drug, up to 9 weeksPopulation: Intent to treat (ITT) population with a global rank available.
Global rank is defined as clinically significant events ranked in order of decreasing perceived severity. Rank descriptions are presented from most to least severe.
Outcome measures
| Measure |
Cohort 1, Sildenafil
n=31 Participants
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-28
|
Cohort 2, Sildenafil
n=29 Participants
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-4, 0.75 mg/kg IV or 1.5 mg/kg enteral on study days 5-6, 1 mg/kg IV or 2 mg/kg enteral on study days 7-28.
A weaning schedule was used following the last study dose on Day 28 or if the patient was withdrawn from the study and escalated to a dose \> 0.5 mg/kg IV or 1 mg/kg enteral. Whether IV or enteral, the weaning schedule was 75% of the last study dose on weaning days 1-2, 50% of the last study dose on weaning days 3-4, 25% of the last study dose on weaning days 5-6, and the weaning schedule was discontinued on weaning day 7.
|
Cohort 3, Sildenafil
n=32 Participants
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-4, 0.75 mg/kg IV or 1.5 mg/kg enteral on study days 5-6, 1 mg/kg IV or 2 mg/kg enteral on study days 7-8, 1.25 mg/kg IV or 2.5 mg/kg enteral on study days 9-10, 1.5 mg/kg IV or 3 mg/kg enteral on study days 11-12, 1.75 mg/kg IV or 3.5 mg/kg enteral on study days 13-14, 2 mg/kg IV or 4 mg/kg enteral on study days 15-28.
A weaning schedule was used following the last study dose on Day 28 or if the patient was withdrawn from the study and escalated to a dose \> 0.5 mg/kg IV or 1 mg/kg enteral. Whether IV or enteral, the weaning schedule was 75% of the last study dose on weaning days 1-2, 50% of the last study dose on weaning days 3-4, 25% of the last study dose on weaning days 5-6, and the weaning schedule was discontinued on weaning day 7.
|
Placebo
n=30 Participants
Placebo (IV or enteral) every 8 hours for 28 days
Placebo: dextrose 5%
|
|---|---|---|---|---|
|
Number of Participants at Each Global Rank
Seizures
|
1 Participants
|
2 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants at Each Global Rank
Dialysis
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants at Each Global Rank
Retinopathy of prematurity (ROP)
|
13 Participants
|
11 Participants
|
18 Participants
|
12 Participants
|
|
Number of Participants at Each Global Rank
Short gut syndrome/intestinal failure
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants at Each Global Rank
Ventriculoperitoneal (VP) shunt
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants at Each Global Rank
Gastrostomy tube
|
4 Participants
|
2 Participants
|
3 Participants
|
1 Participants
|
|
Number of Participants at Each Global Rank
Surgical necrotizing enterocolitis/intestinal perforation (NEC/IP)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants at Each Global Rank
Patent ductus arteriosus (PDA)
|
0 Participants
|
1 Participants
|
2 Participants
|
2 Participants
|
|
Number of Participants at Each Global Rank
Meningitis
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants at Each Global Rank
Sepsis
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants at Each Global Rank
Duration of hospitalization >= 52 weeks PMA
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants at Each Global Rank
Duration of hospitalization 48 - 51 weeks PMA
|
1 Participants
|
3 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants at Each Global Rank
Duration of hospitalization 44 - 47 weeks PMA
|
1 Participants
|
2 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants at Each Global Rank
Duration of hospitalization 40 - 43 weeks PMA
|
2 Participants
|
1 Participants
|
2 Participants
|
2 Participants
|
|
Number of Participants at Each Global Rank
Duration of hospitalization 36 - 39 weeks PMA
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants at Each Global Rank
Mortality
|
0 Participants
|
2 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants at Each Global Rank
Extracorporeal life support
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants at Each Global Rank
Tracheostomy
|
8 Participants
|
3 Participants
|
4 Participants
|
9 Participants
|
|
Number of Participants at Each Global Rank
Periventricular leukomalacia (PVL)
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Cohort 1, Sildenafil
Serious events: 3 serious events
Other events: 0 other events
Deaths: 0 deaths
Cohort 2, Sildenafil
Serious events: 0 serious events
Other events: 0 other events
Deaths: 2 deaths
Cohort 3, Sildenafil
Serious events: 4 serious events
Other events: 0 other events
Deaths: 1 deaths
Placebo
Serious events: 4 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cohort 1, Sildenafil
n=31 participants at risk
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-28.
|
Cohort 2, Sildenafil
n=29 participants at risk
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-4, 0.75 mg/kg IV or 1.5 mg/kg enteral on study days 5-6, 1 mg/kg IV or 2 mg/kg enteral on study days 7-28.
A weaning schedule was used following the last study dose on Day 28 or if the patient was withdrawn from the study and escalated to a dose \> 0.5 mg/kg IV or 1 mg/kg enteral. Whether IV or enteral, the weaning schedule was 75% of the last study dose on weaning days 1-2, 50% of the last study dose on weaning days 3-4, 25% of the last study dose on weaning days 5-6, and the weaning schedule was discontinued on weaning day 7.
|
Cohort 3, Sildenafil
n=32 participants at risk
Sildenafil was administered every eight hours in the following doses: 0.25 mg/kg IV or 0.5 mg/kg enteral on study days 1-2, 0.5 mg/kg IV or 1 mg/kg enteral on study days 3-4, 0.75 mg/kg IV or 1.5 mg/kg enteral on study days 5-6, 1 mg/kg IV or 2 mg/kg enteral on study days 7-8, 1.25 mg/kg IV or 2.5 mg/kg enteral on study days 9-10, 1.5 mg/kg IV or 3 mg/kg enteral on study days 11-12, 1.75 mg/kg IV or 3.5 mg/kg enteral on study days 13-14, 2 mg/kg IV or 4 mg/kg enteral on study days 15-28.
A weaning schedule was used following the last study dose on Day 28 or if the patient was withdrawn from the study and escalated to a dose \> 0.5 mg/kg IV or 1 mg/kg enteral. Whether IV or enteral, the weaning schedule was 75% of the last study dose on weaning days 1-2, 50% of the last study dose on weaning days 3-4, 25% of the last study dose on weaning days 5-6, and the weaning schedule was discontinued on weaning day 7.
|
Placebo
n=30 participants at risk
Placebo (IV or enteral) every 8 hours for 28 days
Placebo: dextrose 5%
|
|---|---|---|---|---|
|
Eye disorders
Retinopathy of prematurity
|
6.5%
2/31 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/29 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/32 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
3.3%
1/30 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
|
Infections and infestations
Pneumonia bacterial
|
0.00%
0/31 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/29 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
3.1%
1/32 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/30 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
|
Infections and infestations
Sepsis
|
0.00%
0/31 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/29 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
3.1%
1/32 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/30 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
|
Infections and infestations
Meningitis bacterial
|
0.00%
0/31 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/29 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/32 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
3.3%
1/30 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
|
Infections and infestations
Streptococcal sepsis
|
0.00%
0/31 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/29 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/32 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
3.3%
1/30 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/31 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/29 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/32 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
3.3%
1/30 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
|
Infections and infestations
Urinary tract infection enterococcal
|
0.00%
0/31 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/29 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/32 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
3.3%
1/30 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
3.2%
1/31 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/29 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/32 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/30 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/31 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/29 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
3.1%
1/32 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/30 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
|
Cardiac disorders
Cardiac dysfunction
|
0.00%
0/31 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/29 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
3.1%
1/32 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/30 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
|
Gastrointestinal disorders
Incarcerated inguinal hernia
|
0.00%
0/31 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/29 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
3.1%
1/32 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/30 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
|
Injury, poisoning and procedural complications
Weaning failure
|
0.00%
0/31 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/29 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/32 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
3.3%
1/30 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
|
Nervous system disorders
Seizure
|
0.00%
0/31 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/29 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
0.00%
0/32 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
3.3%
1/30 • Up to 28 days post last dose of study drug, up to 9 weeks
Serious Adverse Events were collected on the safety population. Non-serious Adverse Events were not collected per protocol.
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place