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

University of North Carolina, Chapel Hill82 enrolled

Overview

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

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

Allocation

RANDOMIZED

Purpose

OTHER

Masking

QUADRUPLE

Enrollment

Conditions

Bronchopulmonary Dysplasia

Interventions

Furosemide Cohort 1DRUG

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.

Furosemide Cohort 2DRUG

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.

Furosemide Cohort 3DRUG

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.

Eligibility

Sex: ALLMin age: 7 DaysMax age: 28 Days

Medical Language ↔ Plain English

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

Locations (21)

Arkansas Children's Hospital/University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Outcomes

Primary Outcomes

Safety as Determined by Adverse Events

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.

Time frame: 35 days for each participant

Secondary Outcomes

Moderate-Severe BPD or Death Risk Throughout Weekly Treatment

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.

Time frame: Risk measured weekly through Week 4

Number of Participants With Moderate-Severe BPD or Death Risk as Clinically Determined

Moderate-severe BPD or death risk was defined using the NICHD Neonatal Research Network BPD outcome estimator.

Time frame: 36 weeks postmenstrual age

Clearance

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.

Time frame: 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.

Volume of Distribution

Data from ClinicalTrials.gov

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