Bronchopulmonary DysplasiaPhase 4PRIMEDNCT05898022
Pragmatic Research on Diuretic Management in Early BPD Pilot
A Phase 4 study testing Furosemide (plus potassium chloride) in people with Bronchopulmonary Dysplasia, run by Children's Hospital Medical Center, Cincinnati at 4 sites in United States.
Trial summary
Babies who are born prematurely often develop a chronic lung disease called bronchopulmonary dysplasia (BPD). BPD puts babies at higher risk for problems with growth and development. Diuretics, such as furosemide, are frequently used in the management of early BPD). Read more about this study
- Who is it for?
- Ages 2 to 10 weeks
- Conditions the study is for
- Bronchopulmonary Dysplasia
- What is being tested?
- Furosemide (plus potassium chloride)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19 participants
- Where
- 4 sitesUnited States
- Study dates
- 17 Aug 2023to 12 Dec 2025
- Phase
- Phase 4
- 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 2 to 10 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- <28 weeks gestation at birth
- Post-Menstrual Age (PMA) of 29-32 weeks gestation
- Requiring invasive positive pressure respiratory support or NIPPV/NIMV and FiO2 ≥ 25% or requiring non-invasive positive pressure respiratory support (NCPAP≥ 5 cm H20, BiPhasic CPAP) and FiO2 ≥ 30%.
- Receiving enteral feedings of 120 mL/kg/day or greater
- Expected to be hospitalized for at least 28 days after enrollment
Who cannot join
- Major congenital anomalies (e.g., known renal anomalies, congenital heart disease, congenital diaphragmatic hernia, or chromosomal anomalies)
- In infants who had electrolyte testing in the week prior to enrollment, those with a serum creatinine > 1.7 mg/dL, BUN >50 mg/dL, Na <125 mmoL/L, K ≤ 2.5 mmol/L, or Ca ≤ 6 mg/dL. Not having electrolyte testing in the week prior to enrollment is not an exclusion criterion.
- Current treatment with Dexamethasone or hydrocortisone for respiratory failure. Treatment with chronic steroids for history of adrenal insufficiency or cardiovascular instability is not an exclusion criterion.
- Treatment with any longer-acting diuretic (e.g., chlorothiazide, hydrochlorothiazide, acetazolamide) within 5 days of enrollment where exposure may result in carryover effects that confound the N-of-1 trial
- Active order for standing, regularly scheduled diuretics (e.g., chronic diuretics)
- Non-English speaking
- Current treatment with ibuprofen or indocin
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Emory University
Atlanta, Georgia, 30303
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, 44106
RTI International
Durham, North Carolina, 27705
About this study
Official title: Pragmatic Research on Diuretic Management in Early Bronchopulmonary Dysplasia (PRIMED) Pilot Study
Babies who are born prematurely often develop a chronic lung disease called bronchopulmonary dysplasia (BPD). BPD puts babies at higher risk for problems with growth and development. Diuretics, such as furosemide, are frequently used in the management of early BPD). Many clinicians use informal trials of therapy to see if a baby responds to diuretics in the short-term before starting chronic diuretic therapy. Despite frequent use of diuretics, it is unclear how many babies truly respond to therapy and if there are long-term benefits of diuretic treatment. Designing research studies to figure this out has been challenging. The Pragmatic Research on Diuretic Management in Early BPD (PRIMED) study is a feasibility pilot study to help us get information to design a larger trial of diuretic management for BPD. Key questions this study will answer include: (1) Can we use an N-of-1 trial to determine whether a particular baby responds to furosemide? In an N-of-1 trial, a baby is switched between furosemide and placebo to compare that particular infant's response on and off diuretics. It is a more rigorous approach to the informal trials of therapy that are often conducted in clinical care. We hope to learn how many babies have a short-term response to furosemide ("responders"); (2) how many babies will still be on respiratory support at the end of the N-of-1 trial? This will help us determine how many patients would be eligible to randomize to chronic diuretic therapy in the second phase of the larger trail, and (3) if a baby is identified as a short-term responder, how many parents and physicians would be willing to randomize the baby to chronic diuretics (3 months) versus placebo in the longer trial?
- Conditions
- Bronchopulmonary Dysplasia
- Being tested
- Furosemide (plus potassium chloride), Placebo (plus placebo electrolyte solution)
- Keywords
- furosemide, ventilator-induced lung injury, lung injury, lung diseases, respiratory tract diseases, infant, premature diseases, newborn, diseases, diuretics
- Medical subject headings
- Bronchopulmonary Dysplasia, Ventilator-Induced Lung Injury, Lung Injury, Lung Diseases, Respiratory Tract Diseases, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Furosemide (plus potassium chloride)Drug
Furosemide is a loop diuretic that inhibits the reabsorption of sodium and chloride in the proximal and distal tubules as well as the loop of Henle. Participants will receive 2 mg/kg enteral furosemide daily during treatment periods when they receive study drug. To prevent hypokalemia and hypochloremia associated with furosemide use, participants will also receive 1 mg/kg of potassium chloride enterally twice per day when receiving furosemide. Each patient will have 8 days of total exposure to furosemide over the 16-day N-of-1 trial.
Placebo (plus placebo electrolyte solution)Drug
During treatment periods when participants receive placebo, they will receive a volume of sterile water equivalent to the study drug dose. Participants will also receive a placebo electrolyte solution equivalent to the volume of potassium chloride that would be given.
| Study group | Role | What they receive |
|---|---|---|
| N-of-1 Trial | Other | Each individual N-of-1 trial will have 2 blocks. In each block patients will crossover between furosemide (plus potassium chloride) for 4 days and placebo (plus placebo electrolyte solution) for 4 days. The total arm length (length of the N-of-1 Trial/Crossover) is 16 days. Patients may receive furosemide (plus potassium chloride) and placebo (plus placebo electrolyte solution) in one of four different treatment order sequences, however, treatment order will not be analyzed for the primary outcomes of feasibility/responder status. Receives: Drug: Furosemide (plus potassium chloride); Drug: Placebo (plus placebo electrolyte solution) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent of Enrolled Infants Who Completed the Full N-of-1 Trial, Remain on Respiratory Support at the Conclusion of the N-of-1 Trial, and Were Identified as a Responder
Measured: 23 Days
Percent of Providers Willing to Support Randomizing a Responder Infant
Measured: 30 Days
Secondary outcomes (6)
Percent of Enrolled Infants Completing Full N-of-1 Trial and Identified as Responder
Measured: 23 days
Percent of Enrolled Infants Completing Full N-of-1 Trial
Measured: 23 days
Percent of Enrolled Infants on Respiratory Support at the Conclusion of the N-of-1 Trial
Measured: 23 days
Rate of Chronic Diuretic Use Among Responders
Measured: 30 days
Rate of Chronic Diuretic Use Among Non-responders
Measured: 30 days
Percent of Parents Willing to Randomize Responder Infant
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2023
- Study start17 Aug 2023
- Primary completion10 Jul 2025
- Study completion12 Dec 2025
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.
- Other trials for Bronchopulmonary DysplasiaStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe 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 4
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- The proposed pilot, feasibility study will enroll patients in a series of N-of-1 trials. Each individual N-of-1 trial will have 2 blocks. In each block patients will crossover between furosemide (plus potassium chloride) for 4 days and placebo (plus placebo electrolyte solution) for 4 days. Each patient will have 8 days of total exposure to furosemide over the 16-day N-of-1 trial.
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- Rainbow Babies and Children's Hospital, Emory University, RTI International, National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Heather Kaplan, Children's Hospital Medical Center, Cincinnati
- Investigators
- Heather Kaplan, MD, MSCE, Principal investigator, Children's Hospital Medical Center, CincinnatiAnna Maria Hibbs, MD, MSCE, Principal investigator, 1. Rainbow Babies and Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05898022
- Sponsor's protocol ID
- 2021-0120
- Other IDs
- R34HL158586-01A1
- Acronym
- PRIMED
- Status last verified
- Mar 2025
- First submitted
- 1 Jun 2023
- Last updated
- 14 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pragmatic Research on Diuretic Management in Early Bronchopulmonary Dysplasia (PRIMED) Pilot Study
- ClinicalTrials.gov ID
- NCT05898022
- Acronym / sponsor ID
- PRIMED / 2021-0120
- Conditions
- Bronchopulmonary Dysplasia
- Keywords
- furosemide, ventilator-induced lung injury, lung injury, lung diseases, respiratory tract diseases, infant, premature diseases, newborn
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- Rainbow Babies and Children's Hospital, Emory University, RTI International, National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 17 Aug 2023 (actual)
- Primary completion
- 10 Jul 2025 (actual)
- Study completion
- 12 Dec 2025 (actual)
- First posted
- 12 Jun 2023 (actual)
- Results
- Posted 14 Jul 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Babies who are born prematurely often develop a chronic lung disease called bronchopulmonary dysplasia (BPD). BPD puts babies at higher risk for problems with growth and development. Diuretics, such as furosemide, are frequently used in the management of early BPD). Many clinicians use informal trials of therapy to see if a baby responds to diuretics in the short-term before starting chronic diuretic therapy. Despite frequent use of diuretics, it is unclear how many babies truly respond to therapy and if there are long-term benefits of diuretic treatment. Designing research studies to figure this out has been challenging. The Pragmatic Research on Diuretic Management in Early BPD (PRIMED) study is a feasibility pilot study to help us get information to design a larger trial of diuretic management for BPD. Key questions this study will answer include: (1) Can we use an N-of-1 trial to determine whether a particular baby responds to furosemide? In an N-of-1 trial, a baby is switched between furosemide and placebo to compare that particular infant's response on and off diuretics. It is a more rigorous approach to the informal trials of therapy that are often conducted in clinical care. We hope to learn how many babies have a short-term response to furosemide ("responders"); (2) how many babies will still be on respiratory support at the end of the N-of-1 trial? This will help us determine how many patients would be eligible to randomize to chronic diuretic therapy in the second phase of the larger trail, and (3) if a baby is identified as a short-term responder, how many parents and physicians would be willing to randomize the baby to chronic diuretics (3 months) versus placebo in the longer trial?
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The proposed pilot, feasibility study will enroll patients in a series of N-of-1 trials. Each individual N-of-1 trial will have 2 blocks. In each block patients will crossover between furosemide (plus potassium chloride) for 4 days and placebo (plus placebo electrolyte solution) for 4 days. Each patient will have 8 days of total exposure to furosemide over the 16-day N-of-1 trial.
| Arm | Type | Receives |
|---|---|---|
| N-of-1 Trial | Other | Drug: Furosemide (plus potassium chloride), Drug: Placebo (plus placebo electrolyte solution)Each individual N-of-1 trial will have 2 blocks. In each block patients will crossover between furosemide (plus potassium chloride) for 4 days and placebo (plus placebo electrolyte solution) for 4 days. The total arm length (length of the N-of-1 Trial/Crossover) is 16 days. Patients may receive furosemide (plus potassium chloride) and placebo (plus placebo electrolyte solution) in one of four different treatment order sequences, however, treatment order will not be analyzed for the primary outcomes of feasibility/responder status. |
Who may qualify
- Ages
- 2 to 10 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- <28 weeks gestation at birth
- Post-Menstrual Age (PMA) of 29-32 weeks gestation
- Requiring invasive positive pressure respiratory support or NIPPV/NIMV and FiO2 ≥ 25% or requiring non-invasive positive pressure respiratory support (NCPAP≥ 5 cm H20, BiPhasic CPAP) and FiO2 ≥ 30%.
- Receiving enteral feedings of 120 mL/kg/day or greater
- Expected to be hospitalized for at least 28 days after enrollment
Key exclusion criteria (7 listed)
- Major congenital anomalies (e.g., known renal anomalies, congenital heart disease, congenital diaphragmatic hernia, or chromosomal anomalies)
- In infants who had electrolyte testing in the week prior to enrollment, those with a serum creatinine > 1.7 mg/dL, BUN >50 mg/dL, Na <125 mmoL/L, K ≤ 2.5 mmol/L, or Ca ≤ 6 mg/dL. Not having electrolyte testing in the week prior to enrollment is not an exclusion criterion.
- Current treatment with Dexamethasone or hydrocortisone for respiratory failure. Treatment with chronic steroids for history of adrenal insufficiency or cardiovascular instability is not an exclusion criterion.
- Treatment with any longer-acting diuretic (e.g., chlorothiazide, hydrochlorothiazide, acetazolamide) within 5 days of enrollment where exposure may result in carryover effects that confound the N-of-1 trial
- Active order for standing, regularly scheduled diuretics (e.g., chronic diuretics)
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 (plus potassium chloride)Furosemide is a loop diuretic that inhibits the reabsorption of sodium and chloride in the proximal and distal tubules as well as the loop of Henle. Participants will receive 2 mg/kg enteral furosemide daily during treatment periods when they receive study drug. To prevent hypokalemia and hypochloremia associated with furosemide use, participants will also receive 1 mg/kg of potassium chloride enterally twice per day when receiving furosemide. Each patient will have 8 days of total exposure to furosemide over the 16-day N-of-1 trial. | Drug | N-of-1 Trial |
| Placebo (plus placebo electrolyte solution)During treatment periods when participants receive placebo, they will receive a volume of sterile water equivalent to the study drug dose. Participants will also receive a placebo electrolyte solution equivalent to the volume of potassium chloride that would be given. | Drug | N-of-1 Trial |
Primary outcome
Percent of Enrolled Infants Who Completed the Full N-of-1 Trial, Remain on Respiratory Support at the Conclusion of the N-of-1 Trial, and Were Identified as a Responder
Time frame: 23 Days
Percent of Providers Willing to Support Randomizing a Responder Infant
Time frame: 30 Days
6 secondary outcomes
Percent of Enrolled Infants Completing Full N-of-1 Trial and Identified as Responder
Time frame: 23 days
Percent of Enrolled Infants Completing Full N-of-1 Trial
Time frame: 23 days
Percent of Enrolled Infants on Respiratory Support at the Conclusion of the N-of-1 Trial
Time frame: 23 days
Rate of Chronic Diuretic Use Among Responders
Time frame: 30 days
Rate of Chronic Diuretic Use Among Non-responders
Time frame: 30 days
Percent of Parents Willing to Randomize Responder Infant
Time frame: 30 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Heather Kaplan, MD, MSCE principal investigator
Children's Hospital Medical Center, Cincinnati
Anna Maria Hibbs, MD, MSCE principal investigator
1. Rainbow Babies and Children's Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Furosemide (plus potassium chloride) in people with Bronchopulmonary Dysplasia, run by Children's Hospital Medical Center, Cincinnati at 4 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 5 inclusion and 7 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 14 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 14 Jul 2026). 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?
Percent of Enrolled Infants Who Completed the Full N-of-1 Trial, Remain on Respiratory Support at the Conclusion of the N-of-1 Trial, and Were Identified as a Responder (time frame: 23 Days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Jul 2026.