Bronchopulmonary DysplasiaPhase 2NCT02527798
Safety of Furosemide in Premature Infants at Risk of Bronchopulmonary Dysplasia (BPD)
A Phase 2 study testing Furosemide Cohort 1, Furosemide Cohort 2 and Furosemide Cohort 3 in people with Bronchopulmonary Dysplasia, run by University of North Carolina, Chapel Hill at 21 sites in United States.
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 Read more about this study
- Who is it for?
- Ages 7 to 28 days
- Conditions the study is for
- Bronchopulmonary Dysplasia
- What is being tested?
- Furosemide Cohort 1, Furosemide Cohort 2 and Furosemide Cohort 3
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 82 participants
- Where
- 21 sitesUnited States
- Study dates
- 27 Nov 2015to 15 Oct 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 to 28 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
21 sites in 1 country.
21 sites in 1 country
United States21 sites
University of Michigan Medical Center
Ann Arbor, Michigan, 48109-4225
Floating Hospital for Children at Tufts Medical Center
Boston, Massachusetts, 02111
The University of North Carolina at Chapel Hill/North Carolina Children's Hospital
Chapel Hill, North Carolina, 27599-7596
University of Illinois at Chicago
Chicago, Illinois, 60612
MetroHealth Medical Center
Cleveland, Ohio, 44109
Nationwide Children's Hospital/The Ohio State University
Columbus, Ohio, 43205
University of Florida Jacskonville Shands Medical Center
Jacksonville, Florida, 32209
Wolfson Children's Hospital
Jacksonville, Florida, 32209
Children's Mercy Hospital and Clinics
Kansas City, Missouri, 64108
University Medical Center of Southern Nevada
Las Vegas, Nevada, 89102
University of Kentucky Medical Center
Lexington, Kentucky, 40536
Arkansas Children's Hospital/University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72202
Loma Linda University Medical Center
Loma Linda, California, 92354
West Virginia University
Morgantown, West Virginia, 26506
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Virginia Commonwealth University
Richmond, Virginia, 23298
South Miami Hospital
South Miami, Florida, 33143
John's Hopkins Al Children's Hospital
St. Petersburg, Florida, 33701
Wesley Medical Center
Wichita, Kansas, 67214
New Hanover Regional Medical Center
Wilmington, North Carolina, 28403
UMass Memorial Medical Center
Worcester, Massachusetts, 01605
About this study
Official title: Safety of Furosemide in Premature Infants at Risk of Bronchopulmonary Dysplasia
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
Read the 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.
- Conditions
- Bronchopulmonary Dysplasia
- Being tested
- Furosemide Cohort 1, Furosemide Cohort 2, Furosemide Cohort 3, Placebo
- Medical subject headings
- Bronchopulmonary Dysplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Furosemide Cohort 1Drug
Also called Lasix
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
Also called Lasix
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
Also called Lasix
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.
PlaceboOther
Also called sugar water
Sugar water will be administered in a equivalent volume as drug intervention.
| Study group | Role | What they receive |
|---|---|---|
| Furosemide Cohort 1 | Experimental | 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. Receives: Drug: Furosemide Cohort 1 |
| Placebo Cohort 1 | Placebo comparator | 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). Receives: Other: Placebo |
| Furosemide Cohort 2 | Experimental | Cohort 2 Infants will receive furosemide (1mg/kg every 6 hours intravenously or 2 mg/kg every 6 hours daily enterally) for 28 days. Receives: Drug: Furosemide Cohort 2 |
| Furosemide Cohort 3 | Experimental | Cohort 3 Infants will receive furosemide (2mg/kg every 6 hours intravenously or 4 mg/kg every 6 hours daily enterally) for 28 days. Receives: Drug: Furosemide Cohort 3 |
| Placebo Cohort 2 | Placebo comparator | 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). Receives: Other: Placebo |
| Placebo Cohort 3 | Placebo comparator | 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). Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 35 days for each participant
Secondary outcomes (6)
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.
Measured: 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.
Measured: 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.
Measured: 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 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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2015 (estimated)
- Study start27 Nov 2015
- Primary completion15 Oct 2019
- Study completion15 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bronchopulmonary DysplasiaStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Duke University, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), The Emmes Company, LLC
- Responsible party
- Sponsor
- Investigators
- Matthew Laughon, MD, MPH, Principal investigator, University of North Carolina, Chapel HillJason E Lang, MD, MPH, Study chair, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02527798
- Sponsor's protocol ID
- 15-1978
- Other IDs
- HHSN27500033, HHSN27500035, 5R01FD005101-02
- Status last verified
- Sep 2021
- First submitted
- 4 Aug 2015
- Last updated
- 28 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 40306549
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety of Furosemide in Premature Infants at Risk of Bronchopulmonary Dysplasia
- ClinicalTrials.gov ID
- NCT02527798
- Acronym / sponsor ID
- 15-1978
- Conditions
- Bronchopulmonary Dysplasia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Duke University, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), The Emmes Company, LLC
- Study start
- 27 Nov 2015 (actual)
- Primary completion
- 15 Oct 2019 (actual)
- Study completion
- 15 Oct 2019 (actual)
- First posted
- 19 Aug 2015 (estimated)
- Results
- Posted 28 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Furosemide Cohort 1 | Experimental | Drug: Furosemide Cohort 1Within 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 1 | Placebo comparator | Other: PlaceboInfants 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 | Experimental | Drug: Furosemide Cohort 2Cohort 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 | Experimental | Drug: Furosemide Cohort 3Cohort 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 2 | Placebo comparator | Other: PlaceboInfants 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 3 | Placebo comparator | Other: PlaceboInfants 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). |
Who may qualify
- Ages
- 7 to 28 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Furosemide Cohort 1Also: Lasixfurosemide 1 mg/kg q 24 hours IV or 2 mg/kg q 24 hours enterally Cohorts will be enrolled sequentially after a safety review. | Drug | Furosemide Cohort 1 |
| Furosemide Cohort 2Also: Lasixfurosemide 1 mg/kg q 6 hours IV or 2 mg/kg q 6 hours enterally Cohorts will be enrolled sequentially after a safety review. | Drug | Furosemide Cohort 2 |
| Furosemide Cohort 3Also: Lasixfurosemide 2 mg/kg q 6 hours IV or 4 mg/kg q 6 hours enterally Cohorts will be enrolled sequentially after a safety review. | Drug | Furosemide Cohort 3 |
| PlaceboAlso: sugar waterSugar water will be administered in a equivalent volume as drug intervention. | Other | Placebo Cohort 1, Placebo Cohort 2, Placebo Cohort 3 |
Primary outcome
Safety as Determined by Adverse Events
Time frame: 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.
6 secondary outcomes
Moderate-Severe BPD or Death Risk Throughout Weekly Treatment
Time frame: Risk measured weekly through Week 4
Number of Participants With Moderate-Severe BPD or Death Risk as Clinically Determined
Time frame: 36 weeks postmenstrual age
Clearance
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
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.
Half-life
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.
Area Under the Plasma Concentration Versus Time Curve
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40306549Greenberg 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthew Laughon, MD, MPH principal investigator
University of North Carolina, Chapel Hill
Jason E Lang, MD, MPH study chair
Duke University
21 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Furosemide Cohort 1, Furosemide Cohort 2 and Furosemide Cohort 3 in people with Bronchopulmonary Dysplasia, run by University of North Carolina, Chapel Hill at 21 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety as Determined by Adverse Events (time frame: 35 days for each participant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02527798, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Dec 2021.