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

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ClinicalTrials.gov Identifier: NCT02527798
Recruitment Status : Active, not recruiting
First Posted : August 19, 2015
Last Update Posted : October 8, 2018
Sponsor:
Collaborators:
Duke University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
The EMMES Corporation
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

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

Condition or disease Intervention/treatment Phase
Bronchopulmonary Dysplasia Drug: Furosemide Cohort 1 Drug: Furosemide Cohort 2 Drug: Furosemide Cohort 3 Other: Placebo Phase 2

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Official Title: Safety of Furosemide in Premature Infants at Risk of Bronchopulmonary Dysplasia
Study Start Date : August 2015
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Furosemide

Arm Intervention/treatment
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




Primary Outcome Measures :
  1. 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 :
  1. 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).

  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]


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:

  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

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): NCT02527798


  Show 21 Study Locations
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
Study Chair: Jason E Lang, MD, MPH Duke University

Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT02527798     History of Changes
Other Study ID Numbers: 15-1978
HHSN27500033 ( Other Grant/Funding Number: NICHD )
HHSN27500035 ( Other Grant/Funding Number: NICHD )
5R01FD005101-02 ( U.S. FDA Grant/Contract )
First Posted: August 19, 2015    Key Record Dates
Last Update Posted: October 8, 2018
Last Verified: October 2018

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