Safety of Sildenafil in Premature Infants

Purpose

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.

Condition

  • Bronchopulmonary Dysplasia

Eligibility

Eligible Ages
Between 7 Days and 28 Days
Eligible Genders
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 - AST > 225 U/L < 72 hours prior to randomization - ALT > 150 U/L < 72 hours prior to randomization

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
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.
  • Drug: Sildenafil
    Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo.
    Other names:
    • Revatio
Placebo Comparator
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.
  • 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).
    Other names:
    • sugar water
Experimental
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.
  • Drug: Sildenafil
    Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo.
    Other names:
    • Revatio
Placebo Comparator
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.
  • 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).
    Other names:
    • sugar water
Experimental
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.
  • Drug: Sildenafil
    Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo.
    Other names:
    • Revatio
Placebo Comparator
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.
  • 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).
    Other names:
    • sugar water

Recruiting Locations

University of Arkansas for Medical Sciences
Little Rock, Arkansas 72205
Contact:
Dalton Janssen
501-364-2391
janssendw@archildrens.org

University of Florida College of Medicine Jacksonville-Wolfson Children's Hospital
Jacksonville, Florida 32209
Contact:
Ashley Maddox
904-244-5450
ashley.maddox@jax.ufl.edu

University of Florida Jacksonville Shands Medical Center
Jacksonville, Florida 32209
Contact:
Ashley Maddox
904-244-5450
ashley.maddox@jax.ufl.edu

Wesley Medical Center
Wichita, Kansas 67214
Contact:
Paula Delmore
316-962-8555
paula.delmore@wesleymc.com

Ochsner Baptist Medical Center
New Orleans, Louisiana 70115
Contact:
Nadrine Hayden
504-897-5811
nadrine.hayden@ochsner.org

Children's Hospital of Nevada at UMC
Las Vegas, Nevada 89106
Contact:
Robert Bimbi
702-245-8389
robert.bimbi@umcsn.com

Golisano Children's Hospital - University of Rochester Medical Center
Rochester, New York 14642
Contact:
Elizabeth Carbonell
585-273-2322
elizabeth_carbonell@urmc.rochester.edu

More Details

NCT ID
NCT03142568
Status
Recruiting
Sponsor
University of North Carolina, Chapel Hill

Study Contact

Matthew M Laughon, MD, MPH
984-974-7851
matt_laughon@med.unc.edu

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.