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

Bronchopulmonary Dysplasia Clinical Trial

Official title:

Safety of Furosemide in Premature Infants at Risk of Bronchopulmonary Dysplasia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02527798
• Other study ID #: 15-1978
• Secondary ID: HHSN27500033HHSN
• Status: Completed
• Phase: Phase 2
• Start date: November 27, 2015
• Est. completion date: October 15, 2019

Study information

• Verified date: September 2021
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: October 15, 2019
• Est. primary completion date: October 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 28 Days

Eligibility

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

Related Conditions & MeSH terms

• Bronchopulmonary Dysplasia

Intervention

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.
• 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.
• 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:
• Placebo
Sugar water will be administered in a equivalent volume as drug intervention.

Locations

Country	Name	City	State
United States	University of Michigan Medical Center	Ann Arbor	Michigan
United States	Floating Hospital for Children at Tufts Medical Center	Boston	Massachusetts
United States	The University of North Carolina at Chapel Hill/North Carolina Children's Hospital	Chapel Hill	North Carolina
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	University of Florida Jacskonville Shands Medical Center	Jacksonville	Florida
United States	Wolfson Children's Hospital	Jacksonville	Florida
United States	Children's Mercy Hospital and Clinics	Kansas City	Missouri
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	University of Kentucky Medical Center	Lexington	Kentucky
United States	Arkansas Children's Hospital/University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Loma Linda University Medical Center	Loma Linda	California
United States	West Virginia University	Morgantown	West Virginia
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Virginia Commonwealth University	Richmond	Virginia
United States	John's Hopkins Al Children's Hospital	Saint Petersburg	Florida
United States	South Miami Hospital	South Miami	Florida
United States	Wesley Medical Center	Wichita	Kansas
United States	New Hanover Regional Medical Center	Wilmington	North Carolina
United States	UMass Memorial Medical Center	Worcester	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	Duke University, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), The Emmes Company, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	35 days for each participant
Secondary	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.	Risk measured weekly through Week 4
Secondary	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.	36 weeks postmenstrual age
Secondary	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.	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.
Secondary	Volume of Distribution	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.	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.
Secondary	Half-life	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.	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.
Secondary	Area Under the Plasma Concentration Versus Time Curve	Population PK data were collected from the two Furosemide cohorts and includes all 39 active drug recipients.	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.