Safety of Sildenafil in Premature Infants
- Registration Number
- NCT03142568
- Lead Sponsor
- University of North Carolina, Chapel Hill
- 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 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 120
- 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
- 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
- AST > 225 U/L < 72 hours prior to randomization
- ALT > 150 U/L < 72 hours prior to randomization
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sildenafil cohort 1 Sildenafil 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 3 Placebo Infants randomized to the placebo treatment group will receive the equivalent of dextrose 5% (sugar water) to be administered IV or enteral use. Placebo cohort 1 Placebo Infants randomized to the placebo treatment group will receive the equivalent of dextrose 5% (sugar water) to be administered IV or enteral use. Placebo cohort 2 Placebo 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 Sildenafil 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 cohort 3 Sildenafil 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.
- Primary Outcome Measures
Name Time Method Safety as determined by adverse event experienced by participants 42 days for each participant Description of safety of sildenafil in premature infants at risk of BDP. Safety will be assessed following initial study-specific procedure e.g., screening blood draws, dosing through 14 days post last study dose and it will be assessed by frequency and incidence of adverse events and serious adverse events.
- Secondary Outcome Measures
Name Time Method Half-Life Samples collected after any dose following completion of 14 days of study drug administration. Half-life \[ Time Frame: 8hr. dosing: time frame: 0-15 min, 30-60 min, 1-2, 2-3, 3-4, 4-5, within 15 min prior to next dose, and 16-24 hrs. after last dose.
Area Under the Curve (AUC) Samples collected after any dose following completion of 14 days of study drug administration. Area under the plasma concentration versus time curve (AUC) of sildenafil. \[Time Frame: 8hr. dosing: time frame: 0-15 min, 30-60 min, 1-2, 2-3, 3-4, 4-5, within 15 min prior to next dose, and 16-24 hrs. after last dose.\]
Volume of Distribution Samples collected after any dose following completion of 14 days of study drug administration. Volume of distribution \[ Time Frame: 8 hr. dosing: time frame: 0-15 min, 30-60 min, 1-2, 2-3, 3-4, 4-5, within 15 min prior to next dose, and 16-24 hrs. after last dose.\]
Clearance Samples collected after any dose following completion of 14 days of study drug administration. Clearance \[ Time Frame:8hr dosing: time frame: 0-15 min, 30-60 min, 1-2, 2-3, 3-4, 4-5, within 15 min prior to next dose, and 16-24 hrs. after last dose.\]
Peak Plasma Concentration Samples collected after any dose following completion of 14 days of study drug administration. Maximum concentration Peak Plasma Concentration (Cmax) of sildenafil \[Time Frame: 8hr. dosing: time frame: 0-15 min, 30-60 min, 1-2, 2-3, 3-4, 4-5, within 15 min prior to next dose, and 16-24 hrs. after last dose.\]
Change in moderate-severe BPD or death risk from baseline 36 weeks postmenstrual age Moderate-severe BPD or death risk will be defined by the NICHD Neonatal Research Network BPD outcome estimator. https://neonatal.rti.org/
The BPD outcome estimator uses the following information to provide individual risk of BPD:
1. Gestational age (weeks)
2. Birth weight (g)
3. Sex
4. Maternal Race/Ethnicity
5. Postnatal day
6. Ventilation type (on the postnatal day of interest)
7. FiO2 (%) (on the postnatal day of interest)
Trial Locations
- Locations (17)
University of Illinois at Chicago
🇺🇸Chicago, Illinois, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
University of Florida Jacksonville Shands Medical Center
🇺🇸Jacksonville, Florida, United States
Health Sciences Centre Hospital
🇨🇦Winnipeg, Manitoba, Canada
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
University of Florida College of Medicine Jacksonville-Wolfson Children's Hospital
🇺🇸Jacksonville, Florida, United States
Monmouth Medical Center
🇺🇸Long Branch, New Jersey, United States
Cohen Children's Medical Center of NY
🇺🇸New Hyde Park, New York, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
WakeMed Health and Hospitals
🇺🇸Raleigh, North Carolina, United States
Ochsner Baptist Medical Center
🇺🇸New Orleans, Louisiana, United States
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Children's Hospital of Nevada at UMC
🇺🇸Las Vegas, Nevada, United States
University of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
Wesley Medical Center
🇺🇸Wichita, Kansas, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Golisano Children's Hospital - University of Rochester Medical Center
🇺🇸Rochester, New York, United States