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Safety of Furosemide in Premature Infants at Risk of Bronchopulmonary Dysplasia (BPD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by University of North Carolina, Chapel Hill
Sponsor:
Collaborators:
Duke University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
The EMMES Corporation
Information provided by (Responsible Party):
Matthew Laughon, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT02527798
First received: August 4, 2015
Last updated: March 17, 2017
Last verified: March 2017
  Purpose

This study will describe the safety of furosemide in premature infants at risk of bronchopulmonary dysplasia and determine the preliminary effectiveness and pharmacokinetics (PK) of furosemide.

Funding Source--FDA Office of Orphan Product Development


Condition Intervention Phase
Bronchopulmonary Dysplasia
Drug: Furosemide Cohort 1
Drug: Furosemide Cohort 2
Drug: Furosemide Cohort 3
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Other
Official Title: Safety of Furosemide in Premature Infants at Risk of Bronchopulmonary Dysplasia

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Safety as determined by adverse event experienced by participants. Description of safety of furosemide in premature infants at risk of BPD [ Time Frame: 35 days for each participant ]
    Safety will be assessed following initial study-specific procedure e.g., screening blood draws, dosing through 7 days post last study dose and it will be assessed by frequency and incidence of adverse events and serious adverse events. A safety monitoring committee (DMC) will be convened by NIH to review data and safety information from study participants throughout the study and prior to dose escalation into cohorts 2 and 3.


Secondary Outcome Measures:
  • 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/index.cfm?fuseaction=BPDCalculator.start).

  • Clearance [ Time Frame: 6 Hr dosing: within 30 min, 2-4 hrs post dose, 12-18 hrs post last dose, within 30 min. prior to next dose. 24 hr dosing: within 30 min., 2-4 , 6-8, 12-16, 20-22 hrs post dose, 48-72 hrs post last dose and within 30 min before next dose ]
  • Volume of distribution [ Time Frame: 6 Hr dosing: within 30 min, 2-4 hrs post dose, 12-18 hrs post last dose, within 30 min. prior to next dose. 24 hr dosing: within 30 min., 2-4 , 6-8, 12-16, 20-22 hrs post dose, 48-72 hrs post last dose and within 30 min before next dose ]
  • Half life [ Time Frame: 6 Hr dosing: within 30 min, 2-4 hrs post dose, 12-18 hrs post last dose, within 30 min. prior to next dose. 24 hr dosing: within 30 min., 2-4 , 6-8, 12-16, 20-22 hrs post dose, 48-72 hrs post last dose and within 30 min before next dose ]
  • Area under the plasma concentration versus time curve (AUC) of furosemide [ Time Frame: 6 Hr dosing: within 30 min, 2-4 hrs post dose, 12-18 hrs post last dose, within 30 min. prior to next dose. 24 hr dosing: within 30 min., 2-4 , 6-8, 12-16, 20-22 hrs post dose, 48-72 hrs post last dose and within 30 min before next dose ]
  • Maximum concentration Peak Plasma Concentration (Cmax) of furosemide [ Time Frame: 6 Hr dosing: within 30 min, 2-4 hrs post dose, 12-18 hrs post last dose, within 30 min. prior to next dose. 24 hr dosing: within 30 min., 2-4 , 6-8, 12-16, 20-22 hrs post dose, 48-72 hrs post last dose and within 30 min before next dose ]

Estimated Enrollment: 120
Study Start Date: August 2015
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Furosemide Cohort 1
Within cohort 1, infants will be randomized using a 3:1 scheme to receive furosemide or placebo. Those randomized to receive furosemide will receive (1mg/kg daily intravenously or 2 mg/kg daily enterally for 28 days.
Drug: Furosemide Cohort 1
furosemide 1 mg/kg q 24 hours IV or 2 mg/kg q 24 hours enterally Cohorts will be enrolled sequentially after a safety review.
Other Name: Lasix
Placebo Comparator: Placebo Cohort 1
Infants randomized to the placebo treatment group will receive the equivalent volume of dextrose 5% for IV use or enteral use (if receiving enteral study drug).
Other: Placebo
Sugar water will be administered in a equivalent volume as drug intervention.
Other Name: sugar water
Experimental: Furosemide Cohort 2
Cohort 2 Infants will receive furosemide (1mg/kg every 6 hours intravenously or 2 mg/kg every 6 hours daily enterally) for 28 days.
Drug: Furosemide Cohort 2
furosemide 1 mg/kg q 6 hours IV or 2 mg/kg q 6 hours enterally Cohorts will be enrolled sequentially after a safety review.
Other Name: Lasix
Experimental: Furosemide Cohort 3
Cohort 3 Infants will receive furosemide (2mg/kg every 6 hours intravenously or 4 mg/kg every 6 hours daily enterally) for 28 days.
Drug: Furosemide Cohort 3
furosemide 2 mg/kg q 6 hours IV or 4 mg/kg q 6 hours enterally Cohorts will be enrolled sequentially after a safety review.
Other Name: Lasix
Placebo Comparator: Placebo Cohort 2
Infants randomized to the placebo treatment group will receive the equivalent volume of dextrose 5% for IV use or enteral use (if receiving enteral study drug).
Other: Placebo
Sugar water will be administered in a equivalent volume as drug intervention.
Other Name: sugar water
Placebo Comparator: Placebo Cohort 3
Infants randomized to the placebo treatment group will receive the equivalent volume of dextrose 5% for IV use or enteral use (if receiving enteral study drug).
Other: Placebo
Sugar water will be administered in a equivalent volume as drug intervention.
Other Name: sugar water

Detailed Description:

Infants will receive a placebo or furosemide for 28 days. Blood samples will be collected for pharmacokinetic analysis.Premature infants will be randomized to receive placebo or furosemide in a dose escalating approach.

Follow up information will be collected up to 7 days after the last dose and at 36 weeks post menstrual age. The final study assessment will occur at the time of discharge, early termination or transfer.

  Eligibility

Ages Eligible for Study:   up to 28 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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)
  2. < 29 weeks gestational age at birth
  3. 7-28 days postnatal age at time of first study dose

Exclusion Criteria:

  1. Exposure to any diuretic ≤ 72 hours prior to first study dose
  2. Previous enrollment and dosing in current study, "Safety of Furosemide in Premature Infants at Risk of Bronchopulmonary Dysplasia"
  3. Hemodynamically significant patent ductus arteriosus, as determined by the investigator
  4. Major congenital anomaly (e.g. congenital diaphragmatic hernia, congenital pulmonary adenomatoid malformation)
  5. Meconium aspiration syndrome
  6. Known allergy to any diuretic
  7. Serum creatinine >1.7 mg/dL < 24 hours prior to first study dose
  8. BUN >50 mg/dL < 24 hours prior to first study dose
  9. Na <125 mmol/L < 24 hours prior to first study dose
  10. K ≤2.5 mmol/L < 24 hours prior to first study dose
  11. Ca ≤ 6 mg/dL < 24 hours prior to first study dose
  12. Indirect bilirubin >10 mg/dL < 24 hours prior to first study dose
  13. Any condition which would make the participant, in the opinion of the investigator, unsuitable for the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02527798

Contacts
Contact: Matthew M. Laughon, MD, MPH 984-974-7851 matt_laughon@med.unc.edu
Contact: Leigh Gosnell, Project Lead 919-668-1280 leigh.gosnell@duke.edu

Locations
United States, Arkansas
Arkansas Children's Hospital/University of Arkansas for Medical Sciences Recruiting
Little Rock, Arkansas, United States, 72202
Principal Investigator: Sherry Courtney, MD         
United States, California
Loma Linda University Medical Center Recruiting
Loma Linda, California, United States, 92354
Principal Investigator: Aprille Febre, MD         
United States, District of Columbia
Childrens National Medical Center Active, not recruiting
Washington, District of Columbia, United States, 20010
United States, Florida
University of Florida Jacskonville Shands Medical Center Recruiting
Jacksonville, Florida, United States, 32209
Principal Investigator: Mark Hudak, MD         
Wolfson Children's Hospital Recruiting
Jacksonville, Florida, United States, 32209
Principal Investigator: Mark Hudak, MD         
United States, Kansas
Wesley Medical Center Active, not recruiting
Wichita, Kansas, United States, 67214
United States, Kentucky
University of Kentucky Medical Center Recruiting
Lexington, Kentucky, United States, 40536
Contact: Mina Hanna, MD       mina.hanna@uky.edu   
Principal Investigator: Mina Hanna, MD         
United States, Massachusetts
Floating Hospital for Children at Tufts Medical Center Recruiting
Boston, Massachusetts, United States, 02111
Principal Investigator: Anijali Lyengar, MD         
United States, Michigan
University of Michigan Medical Center Active, not recruiting
Ann Arbor, Michigan, United States, 48109-4225
United States, North Carolina
The University of North Carolina at Chapel Hill/North Carolina Children's Hospital Recruiting
Chapel Hill, North Carolina, United States, 27599-7596
Contact: Sofia R. Aliaga, MD, MPH    984-974-7846    sofia_aliaga@med.unc.edu   
Principal Investigator: Sofia R. Aliaga, MD, MHP         
New Hanover Regional Medical Center Recruiting
Wilmington, North Carolina, United States, 28403
Principal Investigator: Fernando Moya, MD         
United States, Ohio
Rainbow Babies and Children's Hospital Recruiting
Cleveland, Ohio, United States, 44106
Contact: Andrea Trembath, MD         
Principal Investigator: Andrea Trembath, MD         
MetroHealth Medical Center Recruiting
Cleveland, Ohio, United States, 44109
Principal Investigator: Prem Shekhawat, MD         
United States, Virginia
Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23298
Principal Investigator: Joseph El Khoury, MD         
United States, West Virginia
West Virginia University Recruiting
Morgantown, West Virginia, United States, 26506
Principal Investigator: Autumn Kiefer, 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: Matthew Laughon, Professor of Pediatrics, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT02527798     History of Changes
Other Study ID Numbers: 15-1978
R01FD005101 ( US NIH Grant/Contract Award Number )
Study First Received: August 4, 2015
Last Updated: March 17, 2017

Additional relevant MeSH terms:
Bronchopulmonary Dysplasia
Ventilator-Induced Lung Injury
Lung Injury
Lung Diseases
Respiratory Tract Diseases
Infant, Premature, Diseases
Infant, Newborn, Diseases
Furosemide
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Potassium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on March 24, 2017