Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02527798
Recruitment Status : Active, not recruiting
First Posted : August 19, 2015
Last Update Posted : November 20, 2019
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

Tracking Information
First Submitted Date  ICMJE August 4, 2015
First Posted Date  ICMJE August 19, 2015
Last Update Posted Date November 20, 2019
Study Start Date  ICMJE August 2015
Estimated Primary Completion Date February 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 17, 2015)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02527798 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 17, 2015)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety of Furosemide in Premature Infants at Risk of Bronchopulmonary Dysplasia (BPD)
Official Title  ICMJE Safety of Furosemide in Premature Infants at Risk of Bronchopulmonary Dysplasia
Brief Summary 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 OOPD
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Condition  ICMJE Bronchopulmonary Dysplasia
Intervention  ICMJE
  • 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
  • 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
  • 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
  • Other: Placebo
    Sugar water will be administered in a equivalent volume as drug intervention.
    Other Name: sugar water
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Furosemide Cohort 1
  • 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).
    Intervention: Other: Placebo
  • 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.
    Intervention: Drug: Furosemide Cohort 2
  • 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.
    Intervention: Drug: Furosemide Cohort 3
  • 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).
    Intervention: Other: Placebo
  • 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).
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: August 17, 2015)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2020
Estimated Primary Completion Date February 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 28 Days   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02527798
Other Study ID Numbers  ICMJE 15-1978
HHSN27500033 ( Other Grant/Funding Number: NICHD )
HHSN27500035 ( Other Grant/Funding Number: NICHD )
5R01FD005101-02 ( U.S. FDA Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of North Carolina, Chapel Hill
Study Sponsor  ICMJE University of North Carolina, Chapel Hill
Collaborators  ICMJE
  • Duke University
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  • The Emmes Company, LLC
Investigators  ICMJE
Study Chair: Jason E Lang, MD, MPH Duke University
PRS Account University of North Carolina, Chapel Hill
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP