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Safety of Sildenafil in Premature Infants (SIL02)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03142568
Recruitment Status : Recruiting
First Posted : May 5, 2017
Last Update Posted : May 17, 2023
Sponsor:
Collaborators:
Duke University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
The Emmes Company, LLC
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

Study Description
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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.

Condition or disease Intervention/treatment Phase
Bronchopulmonary Dysplasia Drug: Sildenafil Other: Placebo Phase 2

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Safety of Sildenafil in Premature Infants at Risk of Bronchopulmonary Dysplasia
Actual Study Start Date : April 2, 2018
Estimated Primary Completion Date : February 15, 2024
Estimated Study Completion Date : March 28, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Safety

Arms and Interventions
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Arm Intervention/treatment
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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: sugar water


Outcome Measures
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Primary Outcome Measures :
  1. Safety as determined by adverse event experienced by participants [ Time Frame: 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 :
  1. Volume of Distribution [ Time Frame: 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.]

  2. Clearance [ Time Frame: 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.]

  3. Half-Life [ Time Frame: 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.

  4. Area Under the Curve (AUC) [ Time Frame: 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.]

  5. Peak Plasma Concentration [ Time Frame: 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.]

  6. Change in moderate-severe BPD or death risk from baseline [ Time Frame: 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)


Eligibility Criteria
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Ages Eligible for Study:   7 Days to 28 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03142568


Contacts
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Contact: Matthew M Laughon, MD, MPH 984-974-7851 matt_laughon@med.unc.edu
Contact: Talaya McCright-Gill, MA 321-566-3091 talaya.mccright-gill@duke.edu

Locations
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Sponsors and Collaborators
University of North Carolina, Chapel Hill
Duke University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
The Emmes Company, LLC
Investigators
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Principal Investigator: Matthew M Laughon, MD, MPH University of North Carolina, Chapel Hill
More Information
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Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT03142568    
Other Study ID Numbers: 17-2436
75N94022F00001 ( Other Grant/Funding Number: NICHD )
R01FD006099-01 ( U.S. FDA Grant/Contract )
First Posted: May 5, 2017    Key Record Dates
Last Update Posted: May 17, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Bronchopulmonary Dysplasia
Ventilator-Induced Lung Injury
Lung Injury
Lung Diseases
Respiratory Tract Diseases
Infant, Premature, Diseases
Infant, Newborn, Diseases
 Sildenafil Citrate
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents