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| ID | Type | Description | Link |
|---|---|---|---|
| R34HL158586-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Rainbow Babies and Children's Hospital | OTHER |
| Emory University | OTHER |
| RTI International | OTHER |
| National Heart, Lung, and Blood Institute (NHLBI) |
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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?
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 23 Days | |
| Percent of providers willing to support randomizing a responder infant | 30 Days |
| Measure | Description | Time Frame |
|---|---|---|
| Percent of enrolled infants completing full N-of-1 trial and identified as responder | 23 days | |
| Percent of enrolled infants completing full N-of-1 trial | 23 days | |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Heather Kaplan, MD, MSCE | Children's Hospital Medical Center, Cincinnati | Principal Investigator |
| Anna Maria Hibbs, MD, MSCE | 1. Rainbow Babies and Children's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory University | Atlanta | Georgia | 30303 | United States | ||
| RTI International |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Mar 31, 2026 | Apr 17, 2026 | 7 | ||
| Jun 23, 2026 |
| ID | Term |
|---|---|
| D001997 | Bronchopulmonary Dysplasia |
| D055397 | Ventilator-Induced Lung Injury |
| D055370 | Lung Injury |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D004194 | Disease |
| ID | Term |
|---|---|
| D007235 | Infant, Premature, Diseases |
| D007232 | Infant, Newborn, Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D013898 | Thoracic Injuries |
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| ID | Term |
|---|---|
| D005665 | Furosemide |
| ID | Term |
|---|---|
| D013424 | Sulfanilamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
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| NIH |
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.
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Participant, care provider, investigator, outcomes assessor learn the order of furosemide and placebo administration at the end of their N-of-1 trial.
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| 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. |
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| Percent of enrolled infants on respiratory support at the conclusion of the N-of-1 trial |
| 23 days |
| Percent of parents willing to randomize responder infant | 30 days |
| Rate of chronic diuretic use among responders (and non-responders) | 30 days |
| Durham |
| North Carolina |
| 27705 |
| United States |
| Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | 45229 | United States |
| Case Western Reserve University, Rainbow Babies and Children's Hospital | Cleveland | Ohio | 44106 | United States |
| D014947 | Wounds and Injuries |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000814 |
| Aniline Compounds |
| D000588 | Amines |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |