Safety of Sildenafil in Premature Infants

Bronchopulmonary Dysplasia Clinical Trial

— SIL02  

Official title:

Safety of Sildenafil in Premature Infants at Risk of Bronchopulmonary Dysplasia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03142568
• Other study ID #: 17-2436
• Secondary ID: 75N94022F00001R0
• Status: Recruiting
• Phase: Phase 2
• Start date: April 2, 2018
• Est. completion date: March 2025

Study information

• Verified date: May 2024
• Source: University of North Carolina, Chapel Hill
• Contact: Matthew M Laughon, MD, MPH
• Phone: 984-974-7851
• Email: matt_laughon[@]med.unc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: March 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Days to 28 Days

Eligibility

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

• AST > 225 U/L < 72 hours prior to randomization

• ALT > 150 U/L < 72 hours prior to randomization

Related Conditions & MeSH terms

• Bronchopulmonary Dysplasia

Intervention

Drug:
• Sildenafil
Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo.

Other:
• 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).

Locations

Country	Name	City	State
Canada	Health Sciences Centre Hospital	Winnipeg	Manitoba
United States	University of Illinois at Chicago	Chicago	Illinois
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	University of Florida College of Medicine Jacksonville-Wolfson Children's Hospital	Jacksonville	Florida
United States	University of Florida Jacksonville Shands Medical Center	Jacksonville	Florida
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 Kentucky	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
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	Ochsner Baptist Medical Center	New Orleans	Louisiana
United States	University of Oklahoma	Oklahoma City	Oklahoma
United States	WakeMed Health and Hospitals	Raleigh	North Carolina
United States	Golisano Children's Hospital - University of Rochester Medical Center	Rochester	New York
United States	Wesley Medical Center	Wichita	Kansas

Sponsors (4)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	Duke University, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), The Emmes Company, LLC

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety as determined by adverse event experienced by participants	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.	42 days for each participant
Secondary	Volume of Distribution	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.]	Samples collected after any dose following completion of 14 days of study drug administration.
Secondary	Clearance	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.]	Samples collected after any dose following completion of 14 days of study drug administration.
Secondary	Half-Life	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.	Samples collected after any dose following completion of 14 days of study drug administration.
Secondary	Area Under the Curve (AUC)	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.]	Samples collected after any dose following completion of 14 days of study drug administration.
Secondary	Peak Plasma Concentration	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.]	Samples collected after any dose following completion of 14 days of study drug administration.
Secondary	Change in moderate-severe BPD or death risk from baseline	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: Gestational age (weeks); Birth weight (g); Sex; Maternal Race/Ethnicity; Postnatal day; Ventilation type (on the postnatal day of interest); FiO2 (%) (on the postnatal day of interest)	36 weeks postmenstrual age