Safety of Furosemide in Premature Infants at Risk of Bronchopulmonary Dysplasia (BPD)
- Conditions
- Bronchopulmonary Dysplasia
- Interventions
- Registration Number
- NCT02527798
- Lead Sponsor
- 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
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 82
- 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 days postnatal age at time of first study dose
- Exposure to any diuretic ≤ 72 hours prior to first study dose
- Previous enrollment and dosing in current study, "Safety of Furosemide in Premature Infants at Risk of Bronchopulmonary Dysplasia"
- Hemodynamically significant patent ductus arteriosus, as determined by the investigator
- Major congenital anomaly (e.g. congenital diaphragmatic hernia, congenital pulmonary adenomatoid malformation)
- Meconium aspiration syndrome
- Known allergy to any diuretic
- Serum creatinine >1.7 mg/dL < 24 hours prior to first study dose
- BUN >50 mg/dL < 24 hours prior to first study dose
- Na <125 mmol/L < 24 hours prior to first study dose
- K ≤2.5 mmol/L < 24 hours prior to first study dose
- Ca ≤ 6 mg/dL < 24 hours prior to first study dose
- Indirect bilirubin >10 mg/dL < 24 hours prior to first study dose
- Any condition which would make the participant, in the opinion of the investigator, unsuitable for the study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Furosemide Cohort 1 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. Placebo Cohort 2 Placebo 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). Placebo Cohort 1 Placebo 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). Furosemide Cohort 2 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. Furosemide Cohort 3 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. Placebo Cohort 3 Placebo 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).
- Primary Outcome Measures
Name Time Method Safety as Determined by Adverse Events 35 days for each participant Safety was assessed following the initial study-specific procedure (e.g., screening blood draws, dosing) through 7 days post last study dose by frequency and incidence of adverse events and serious adverse events.
- Secondary Outcome Measures
Name Time Method Clearance After study drug administration completion within 30 minutes, 2-4 hours, 6-8 hours, 12-16 hours, and 20-22 hours; within 30 minutes prior to the next dose; and within 48-72 hours of the final study drug administration. Data was collected from Furosemide/Active Cohort 1 and Cohort 2 and combined Cohorts. In total 39 active drug recipients participated. PK samples were collected after 7 days on study drug at recommended time points through 28 days on study drug plus one elimination (post drug discontinuation) time point.
Moderate-Severe BPD or Death Risk Throughout Weekly Treatment Risk measured weekly through Week 4 Moderate-severe BPD or death risk was defined by the NICHD Neonatal Research Network (NRN) BPD outcome estimator which provides an estimate of the risk of BPD (none, mild, moderate, severe) or death by postnatal day and is presented as a percentage. For this protocol, the categories were dichotomized to none-mild vs. moderate-severe-death. The risk of BPD or death was defined by the NICHD NRN BPD estimator on days 7, 14, 21 and 28 of study drug using the closest day available from the BPD estimator. The BPD estimator includes infants up to 28 postnatal days; for infants in this protocol older than that, 28-day estimates are used.
Area Under the Plasma Concentration Versus Time Curve After study drug administration completion within 30 minutes, 2-4 hours, 6-8 hours, 12-16 hours, and 20-22 hours; within 30 minutes prior to the next dose; and within 48-72 hours of the final study drug administration. Population PK data were collected from the two Furosemide cohorts and includes all 39 active drug recipients.
Number of Participants With Moderate-Severe BPD or Death Risk as Clinically Determined 36 weeks postmenstrual age Moderate-severe BPD or death risk was defined using the NICHD Neonatal Research Network BPD outcome estimator.
Volume of Distribution After study drug administration completion within 30 minutes, 2-4 hours, 6-8 hours, 12-16 hours, and 20-22 hours; within 30 minutes prior to the next dose; and within 48-72 hours of the final study drug administration. Data was collected from Furosemide/Active Cohort 1 and Cohort 2 and combined Cohorts. In total 39 active drug recipients participated. PK samples were collected after 7 days on study drug at recommended time points through 28 days on study drug plus one elimination (post drug discontinuation) time point.
Half-life After study drug administration completion within 30 minutes, 2-4 hours, 6-8 hours, 12-16 hours, and 20-22 hours; within 30 minutes prior to the next dose; and within 48-72 hours of the final study drug administration. Data was collected from Furosemide/Active Cohort 1 and Cohort 2 and combined Cohorts. In total 39 active drug recipients participated. PK samples were collected after 7 days on study drug at recommended time points through 28 days on study drug plus one elimination (post drug discontinuation) time point.
Trial Locations
- Locations (21)
West Virginia University
🇺🇸Morgantown, West Virginia, United States
University of Illinois at Chicago
🇺🇸Chicago, Illinois, United States
MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
Nationwide Children's Hospital/The Ohio State University
🇺🇸Columbus, Ohio, United States
John's Hopkins Al Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
University of Florida Jacskonville Shands Medical Center
🇺🇸Jacksonville, Florida, United States
New Hanover Regional Medical Center
🇺🇸Wilmington, North Carolina, United States
South Miami Hospital
🇺🇸South Miami, Florida, United States
University of Kentucky Medical Center
🇺🇸Lexington, Kentucky, United States
Floating Hospital for Children at Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
UMass Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
Wesley Medical Center
🇺🇸Wichita, Kansas, United States
Arkansas Children's Hospital/University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
University of Michigan Medical Center
🇺🇸Ann Arbor, Michigan, United States
Children's Mercy Hospital and Clinics
🇺🇸Kansas City, Missouri, United States
University Medical Center of Southern Nevada
🇺🇸Las Vegas, Nevada, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
The University of North Carolina at Chapel Hill/North Carolina Children's Hospital
🇺🇸Chapel Hill, North Carolina, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Wolfson Children's Hospital
🇺🇸Jacksonville, Florida, United States