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

NCT ID: NCT02527798

Last Updated: 2021-12-28

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

82 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-27

Study Completion Date

2019-10-15

Brief Summary

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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

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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.

Conditions

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Bronchopulmonary Dysplasia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

Furosemide Cohort 1

Intervention Type DRUG

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.

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).

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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

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.

Group Type EXPERIMENTAL

Furosemide Cohort 2

Intervention Type DRUG

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

Cohort 3 Infants will receive furosemide (2mg/kg every 6 hours intravenously or 4 mg/kg every 6 hours daily enterally) for 28 days.

Group Type EXPERIMENTAL

Furosemide Cohort 3

Intervention Type DRUG

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.

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).

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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

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).

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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

Interventions

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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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Placebo

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

Intervention Type OTHER

Other Intervention Names

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Lasix Lasix Lasix sugar water

Eligibility Criteria

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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
Minimum Eligible Age

7 Days

Maximum Eligible Age

28 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Duke University

OTHER

Sponsor Role collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

The Emmes Company, LLC

INDUSTRY

Sponsor Role collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Matthew Laughon, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Jason E Lang, MD, MPH

Role: STUDY_CHAIR

Duke University

Locations

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

Little Rock, Arkansas, United States

Site Status

Loma Linda University Medical Center

Loma Linda, California, United States

Site Status

University of Florida Jacskonville Shands Medical Center

Jacksonville, Florida, United States

Site Status

Wolfson Children's Hospital

Jacksonville, Florida, United States

Site Status

South Miami Hospital

South Miami, Florida, United States

Site Status

John's Hopkins Al Children's Hospital

St. Petersburg, Florida, United States

Site Status

University of Illinois at Chicago

Chicago, Illinois, United States

Site Status

Wesley Medical Center

Wichita, Kansas, United States

Site Status

University of Kentucky Medical Center

Lexington, Kentucky, United States

Site Status

Floating Hospital for Children at Tufts Medical Center

Boston, Massachusetts, United States

Site Status

UMass Memorial Medical Center

Worcester, Massachusetts, United States

Site Status

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Site Status

Children's Mercy Hospital and Clinics

Kansas City, Missouri, United States

Site Status

University Medical Center of Southern Nevada

Las Vegas, Nevada, United States

Site Status

The University of North Carolina at Chapel Hill/North Carolina Children's Hospital

Chapel Hill, North Carolina, United States

Site Status

New Hanover Regional Medical Center

Wilmington, North Carolina, United States

Site Status

MetroHealth Medical Center

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital/The Ohio State University

Columbus, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

West Virginia University

Morgantown, West Virginia, United States

Site Status

Countries

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United States

References

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Greenberg RG, Lang J, Smith PB, Shekhawat P, Courtney SE, Hudak ML, Moya F, Iyengar A, Eldemerdash A, Bloom B, Go M, Hanna M, Rhein L, Aliaga S, Lewis T, Febre A, Kiefer AS, Bhatt-Mehta V, Khoury JA, Selewski D, Anand R, Martz K, Payne EH, Zimmerman KO, Benjamin DK Jr, Laughon M; Best Pharmaceuticals for Children Act - Pediatric Trials Network Steering Committee. Furosemide Safety in Preterm Infants at Risk for Bronchopulmonary Dysplasia: A Randomized Clinical Trial. J Pediatr. 2025 Aug;283:114629. doi: 10.1016/j.jpeds.2025.114629. Epub 2025 Apr 28.

Reference Type DERIVED
PMID: 40306549 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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HHSN27500033

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

HHSN27500035

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

5R01FD005101-02

Identifier Type: FDA

Identifier Source: secondary_id

View Link

15-1978

Identifier Type: -

Identifier Source: org_study_id