Safety of Sildenafil in Premature Infants at Risk of Bronchopulmonary Dysplasia
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 109
- Locations
- 15
- Primary Endpoint
- Safety as Determined by Adverse Event Experienced by Participants
Study Overview
Brief Summary
Describe the safety of sildenafil in premature infants at risk of bronchopulmonary dysplasia and determine preliminary effectiveness and pharmacokinetics (PK) of sildenafil. Funding Source - FDA Office of Orphan Products Development (OOPD).
Detailed Description
This will be a multi-center, randomized, placebo-controlled, sequential dose escalating, double masked, safety data study of sildenafil in premature infants.
This is a Phase II study design, premature infants (inpatient in neonatal intensive care units) will be randomized in a dose escalating approach 3:1 (sildenafil: placebo) into 3 cohorts with escalating doses of sildenafil. There will be 40 randomized and dosed participants in each cohort for a total of up to 120 participants. Cohort 1 sildenafil dose will be 0.125 mg/kg q 8 hours IV or 0.25 mg/kg q 8 hours enteral. Cohort 2 sildenafil dose will be 0.5 mg/kg q 8 hours IV or 1.0 mg/kg q 8 hours enteral. Cohort 3 sildenafil dose will be 1 mg/kg q 8 hours IV or 2 mg/kg q 8 hours enteral.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 7 Days to 28 Days (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Receiving positive airway pressure (nasal continuous airway pressure, nasal intermittent positive pressure ventilation, or nasal cannula flow > 1LPM) or mechanical ventilation (high frequency or conventional)
- •<29 weeks gestational age at birth
- •7-28 (inclusive) days postnatal age at time of randomization
Exclusion Criteria
- •Currently receiving vasopressors
- •Currently receiving inhaled nitric oxide
- •Baseline mean arterial pressure < gestational age (in weeks) plus postnatal age (in weeks) within 2 hours of sildenafil administration
- •Known allergy to sildenafil
- •Known sickle cell disease
- •Aspartate Aminotransferase (AST) > 225 U/L < 72 hours prior to randomization
- •Alanine Aminotransferase (ALT) > 150 U/L < 72 hours prior to randomization
Arms & Interventions
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.
Intervention: Placebo (Other)
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.
Intervention: Placebo (Other)
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.
Intervention: Placebo (Other)
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.
Intervention: Sildenafil (Drug)
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.
Intervention: Sildenafil (Drug)
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.
Intervention: Sildenafil (Drug)
Outcomes
Primary Outcomes
Safety as Determined by Adverse Event Experienced by Participants
Time Frame: Nonserious adverse events were collected through Day 14 following last study intervention. Serious adverse events were collected through Day 28 following last study intervention. Retinopathy of prematurity was assessed through hospital discharge/transfer.
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.
Secondary Outcomes
- Volume of Distribution(Pharmacokinetic samples were collected after any dose following completion of 7 days of study drug administration through Day 28 of study drug administration.)
- Clearance(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(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)(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(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(From the first day of study drug administration to the end of study drug administration, up to 28 days)