Clinical trial NCT03142568: Safety of Sildenafil in Premature Infants
Official title: Safety of Sildenafil in Premature Infants at Risk of Bronchopulmonary Dysplasia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bronchopulmonary Dysplasia
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Duke University
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: The Emmes Company, LLC
First posted: 2017-05-05
Enrollment: 106
Sex: ALL
Minimum age (years): 7
Maximum age (years): 28
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety as determined by adverse event experienced by participants
timeFrame: 42 days for each participant
Secondary outcomes:
measure: Volume of Distribution
timeFrame: Samples collected after any dose following completion of 14 days of study drug administration.
measure: Clearance
timeFrame: Samples collected after any dose following completion of 14 days of study drug administration.
measure: Half-Life
timeFrame: Samples collected after any dose following completion of 14 days of study drug administration.
measure: Area Under the Curve (AUC)
timeFrame: Samples collected after any dose following completion of 14 days of study drug administration.
measure: Peak Plasma Concentration
timeFrame: Samples collected after any dose following completion of 14 days of study drug administration.
measure: Change in moderate-severe BPD or death risk from baseline
timeFrame: 36 weeks postmenstrual age
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Jacksonville
country: United States
facility: University of Florida College of Medicine Jacksonville-Wolfson Children's Hospital
state: Florida
city: Jacksonville
country: United States
facility: University of Florida Jacksonville Shands Medical Center
state: Florida
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Wichita
country: United States
facility: Wesley Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Baptist Medical Center
state: Louisiana
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Las Vegas
country: United States
facility: Children's Hospital of Nevada at UMC
state: Nevada
city: Long Branch
country: United States
facility: Monmouth Medical Center
state: New Jersey
city: New Hyde Park
country: United States
facility: Cohen Children's Medical Center of NY
state: New York
city: Rochester
country: United States
facility: Golisano Children's Hospital - University of Rochester Medical Center
state: New York
city: Raleigh
country: United States
facility: WakeMed Health and Hospitals
state: North Carolina
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Winnipeg
country: Canada
facility: Health Sciences Centre Hospital
state: Manitoba
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Matthew M Laughon, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: