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Safety of Sildenafil in Premature Infants (SIL02)

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ClinicalTrials.gov Identifier: NCT03142568
Recruitment Status : Recruiting
First Posted : May 5, 2017
Last Update Posted : January 5, 2018
Sponsor:
Collaborators:
Information provided by (Responsible Party):

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.

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

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
Anticipated Study Start Date : January 2018
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : August 2019

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

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

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

Information from the National Library of Medicine

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Ages Eligible for Study:   up 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

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
Contact: Matthew M Laughon, MD, MPH 984-974-7851 matt_laughon@med.unc.edu
Contact: Mary Mills, BS 919-668-8819 mary.mills2@duke.edu

Locations
United States, Louisiana
Ochsner Baptist Medical Center Not yet recruiting
New Orleans, Louisiana, United States, 70115
Principal Investigator: Amanda England, MD         
United States, Nevada
Children's Hospital of Nevada at UMC Not yet recruiting
Las Vegas, Nevada, United States, 89106
Contact: Ronald Roemer    702-207-8345    Ronald.Roemer@umcsn.com   
Principal Investigator: Alaa Eldemerdash, MD         
United States, New York
Golisano Children's Hospital - University of Rochester Medical Center Recruiting
Rochester, New York, United States, 14642
Principal Investigator: Gloria Pryhuber, MD         
United States, North Carolina
WakeMed Health and Hospitals Not yet recruiting
Raleigh, North Carolina, United States, 27610
Principal Investigator: Stephen Kicklighter, MD         
United States, Ohio
Cincinnati Childrens Hospital Medical Center Not yet recruiting
Cincinnati, Ohio, United States, 45229
Principal Investigator: Brenda Poindexter, MD         
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 Corporation
Investigators
Principal Investigator: Matthew M Laughon, MD, MPH University of North Carolina, Chapel Hill
More Information

Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT03142568     History of Changes
Other Study ID Numbers: 00069705
HHSN27500039 ( Other Grant/Funding Number: NICHD )
First Posted: May 5, 2017    Key Record Dates
Last Update Posted: January 5, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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