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

Description

Screening/Baseline

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

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

Treatment Period

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

1. Actual weight on study Days 7 (± 1 day), 14 (± 1 day), 21 (± 1 day), and 28 (± 1 day) of study drug administration
2. Date, time, amount, and route of study drug dose
3. All concomitant medications
4. MAP
5. All MAP values obtained 24 hours after the first dose of study drug regardless of administration route.
6. MAP values will be obtained at a minimum at the following time points i. Prior to the first dose of study drug or dose escalation: 2 hours (± 5 minutes), 1 hour (± 5 minutes), and 15 minutes (± 5 minutes) ii. If administration route is IV:
7. During and following the first dose of study drug or dose escalation: MAP at start of infusion, every 15 minutes (± 5 minutes) during infusion, at end of infusion (inclusive of flush) (± 5 minutes), at 15 and 30 minutes (± 5 minutes) after end of infusion, hourly (± 15 minutes) for 4 hours, and once in the remaining 2 hours prior to the next dose.
8. For subsequent IV doses, the lowest valid MAP value should be recorded daily while on study drug.

iii. If the administration route is enteral:

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

Weaning Period (Cohorts 2 and 3)

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

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

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

Follow-up Period

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

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

Final Study Assessment

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

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

Details