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Safety of Sildenafil in Premature Infants (SIL02)

Primary Purpose

Bronchopulmonary Dysplasia

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Sildenafil
Placebo
Sponsored by
University of North Carolina, Chapel Hill
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bronchopulmonary Dysplasia

Eligibility Criteria

7 Days - 28 Days (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Arkansas for Medical SciencesRecruiting
  • University of Florida College of Medicine Jacksonville-Wolfson Children's HospitalRecruiting
  • University of Florida Jacksonville Shands Medical CenterRecruiting
  • University of Illinois at Chicago
  • Wesley Medical CenterRecruiting
  • University of Kentucky
  • Ochsner Baptist Medical CenterRecruiting
  • University of Mississippi Medical Center
  • Children's Mercy Hospital
  • Children's Hospital of Nevada at UMCRecruiting
  • Hackensack University Medical Center
  • Monmouth Medical Center
  • Cohen Children's Medical Center of NY
  • Golisano Children's Hospital - University of Rochester Medical CenterRecruiting
  • WakeMed Health and Hospitals
  • University of Oklahoma
  • Health Sciences Centre HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Sildenafil cohort 1

Placebo cohort 1

Sildenafil cohort 2

Placebo cohort 2

Sildenafil cohort 3

Placebo cohort 3

Arm Description

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.

Infants randomized to the placebo treatment group will receive the equivalent of dextrose 5% (sugar water) to be administered IV or enteral use.

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.

Infants randomized to the placebo treatment group will receive the equivalent of dextrose 5% (sugar water) to be administered IV or enteral use.

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.

Infants randomized to the placebo treatment group will receive the equivalent of dextrose 5% (sugar water) to be administered IV or enteral use.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.]
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.]
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.
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.]
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.]
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)

Full Information

First Posted
April 17, 2017
Last Updated
May 16, 2023
Sponsor
University of North Carolina, Chapel Hill
Collaborators
Duke University, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), The Emmes Company, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT03142568
Brief Title
Safety of Sildenafil in Premature Infants
Acronym
SIL02
Official Title
Safety of Sildenafil in Premature Infants at Risk of Bronchopulmonary Dysplasia
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 2, 2018 (Actual)
Primary Completion Date
February 15, 2024 (Anticipated)
Study Completion Date
March 28, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of North Carolina, Chapel Hill
Collaborators
Duke University, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), The Emmes Company, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bronchopulmonary Dysplasia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Sildenafil cohort 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo cohort 1
Arm Type
Placebo Comparator
Arm Description
Infants randomized to the placebo treatment group will receive the equivalent of dextrose 5% (sugar water) to be administered IV or enteral use.
Arm Title
Sildenafil cohort 2
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo cohort 2
Arm Type
Placebo Comparator
Arm Description
Infants randomized to the placebo treatment group will receive the equivalent of dextrose 5% (sugar water) to be administered IV or enteral use.
Arm Title
Sildenafil cohort 3
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo cohort 3
Arm Type
Placebo Comparator
Arm Description
Infants randomized to the placebo treatment group will receive the equivalent of dextrose 5% (sugar water) to be administered IV or enteral use.
Intervention Type
Drug
Intervention Name(s)
Sildenafil
Other Intervention Name(s)
Revatio
Intervention Description
Infants will be randomized using a 3:1 scheme to receive sildenafil or placebo.
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
sugar water
Intervention Description
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).
Primary Outcome Measure Information:
Title
Safety as determined by adverse event experienced by participants
Description
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.
Time Frame
42 days for each participant
Secondary Outcome Measure Information:
Title
Volume of Distribution
Description
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.]
Time Frame
Samples collected after any dose following completion of 14 days of study drug administration.
Title
Clearance
Description
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.]
Time Frame
Samples collected after any dose following completion of 14 days of study drug administration.
Title
Half-Life
Description
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.
Time Frame
Samples collected after any dose following completion of 14 days of study drug administration.
Title
Area Under the Curve (AUC)
Description
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.]
Time Frame
Samples collected after any dose following completion of 14 days of study drug administration.
Title
Peak Plasma Concentration
Description
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.]
Time Frame
Samples collected after any dose following completion of 14 days of study drug administration.
Title
Change in moderate-severe BPD or death risk from baseline
Description
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)
Time Frame
36 weeks postmenstrual age

10. Eligibility

Sex
All
Minimum Age & Unit of Time
7 Days
Maximum Age & Unit of Time
28 Days
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Matthew M Laughon, MD, MPH
Phone
984-974-7851
Email
matt_laughon@med.unc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Talaya McCright-Gill, MA
Phone
321-566-3091
Email
talaya.mccright-gill@duke.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthew M Laughon, MD, MPH
Organizational Affiliation
University of North Carolina, Chapel Hill
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dalton Janssen
Phone
501-364-2391
Email
janssendw@archildrens.org
First Name & Middle Initial & Last Name & Degree
Gina Hawkins
Phone
501-364-2598
Email
hawkinsga@archildrens.org
First Name & Middle Initial & Last Name & Degree
Ankita Shukla, MD
Facility Name
University of Florida College of Medicine Jacksonville-Wolfson Children's Hospital
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ashley Maddox
Phone
904-244-5450
Email
ashley.maddox@jax.ufl.edu
First Name & Middle Initial & Last Name & Degree
Shelly Crawford
Phone
904-244-5290
Email
shelly.crawford@jax.ufl.edu
First Name & Middle Initial & Last Name & Degree
Mark Hudak, MD
Facility Name
University of Florida Jacksonville Shands Medical Center
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ashley Maddox
Phone
904-244-5450
Email
ashley.maddox@jax.ufl.edu
First Name & Middle Initial & Last Name & Degree
Shelley Crawford
Phone
904-244-5290
Email
shelly.crawford@jax.ufl.edu
First Name & Middle Initial & Last Name & Degree
Mark Hudak, MD
Facility Name
University of Illinois at Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Individual Site Status
Completed
Facility Name
Wesley Medical Center
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paula Delmore
Phone
316-962-8555
Email
paula.delmore@wesleymc.com
First Name & Middle Initial & Last Name & Degree
Lela Hernandez
Phone
316-962-6905
Email
lela.hernandez@wesleymc.com
First Name & Middle Initial & Last Name & Degree
Barry Bloom, MD
Facility Name
University of Kentucky
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40356
Country
United States
Individual Site Status
Completed
Facility Name
Ochsner Baptist Medical Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nadrine Hayden
Phone
504-897-5811
Email
nadrine.hayden@ochsner.org
First Name & Middle Initial & Last Name & Degree
Joan Cooper
Phone
504-897-5882
Email
joan.cooper@ochsner.org
First Name & Middle Initial & Last Name & Degree
Amanda England, MD
Facility Name
University of Mississippi Medical Center
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Individual Site Status
Completed
Facility Name
Children's Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Individual Site Status
Withdrawn
Facility Name
Children's Hospital of Nevada at UMC
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89106
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robert Bimbi
Phone
702-245-8389
Email
robert.bimbi@umcsn.com
First Name & Middle Initial & Last Name & Degree
Jennifer Robinson
Phone
702-383-7842
Email
jennifer.robinson@umcsn.com
First Name & Middle Initial & Last Name & Degree
Alaa Eldemerdash, MD
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Individual Site Status
Withdrawn
Facility Name
Monmouth Medical Center
City
Long Branch
State/Province
New Jersey
ZIP/Postal Code
07740
Country
United States
Individual Site Status
Completed
Facility Name
Cohen Children's Medical Center of NY
City
New Hyde Park
State/Province
New York
ZIP/Postal Code
11040
Country
United States
Individual Site Status
Completed
Facility Name
Golisano Children's Hospital - University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elizabeth Carbonell
Phone
585-273-2322
Email
elizabeth_carbonell@urmc.rochester.edu
First Name & Middle Initial & Last Name & Degree
Tanya Scalise
Phone
585-275-4166
Email
tanya_scalise@urmc.rochester.edu
First Name & Middle Initial & Last Name & Degree
Gloria Pryhuber, MD
Facility Name
WakeMed Health and Hospitals
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27610
Country
United States
Individual Site Status
Completed
Facility Name
University of Oklahoma
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Individual Site Status
Completed
Facility Name
Health Sciences Centre Hospital
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3A 1R9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jeannine Schellenberg
Phone
204-789-3206
Email
jschellenberg@mich.ca
First Name & Middle Initial & Last Name & Degree
Beata Kozak
Phone
204-787-4542
Email
bkozak@exchange.hsc.mb.ca
First Name & Middle Initial & Last Name & Degree
Michael Narvey, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Safety of Sildenafil in Premature Infants

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