Pragmatic Research on Diuretic Management in Early BPD Pilot

NCT05898022 | Completed Phase 4 DMC FDA Drug

• 2 other identifiers: 2021-0120R34HL158586-01A1
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 4

Brief 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). 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

Keywords

furosemide; ventilator-induced lung injury; lung injury; lung diseases; respiratory tract diseases; infant; premature diseases; newborn; diseases; diuretics

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (5)

• 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

• 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

Study Arms (1)

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.

Drug: Furosemide (plus potassium chloride); Drug: Placebo (plus placebo electrolyte solution)

Interventions

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.

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.

N-of-1 Trial

Eligibility Criteria

• Age: 2 Weeks - 10 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• \<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

You may not qualify if:

• Major congenital anomalies (e.g., known renal anomalies, congenital heart disease, congenital diaphragmatic hernia, or chromosomal anomalies)
• 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

Sponsors & Collaborators

• Emory University: collaborator
• Children's Hospital Medical Center, Cincinnati: lead
• Rainbow Babies and Children's Hospital: collaborator
• RTI International: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (4)

Emory University

Atlanta, Georgia, 30303, United States

Location

RTI International

Durham, North Carolina, 27705, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Case Western Reserve University, Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

Bronchopulmonary Dysplasia; Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Disease

Interventions

Furosemide

Condition Hierarchy (Ancestors)

Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Thoracic Injuries; Wounds and Injuries; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfanilamides; Sulfonamides; Amides; Organic Chemicals; Aniline Compounds; Amines; Sulfones; Sulfur Compounds

Study Officials

• 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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Masking Details: Participant, care provider, investigator, outcomes assessor learn the order of furosemide and placebo administration at the end of their N-of-1 trial.
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Model Details: 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.

Study Record Dates

• First Submitted: June 1, 2023
• First Posted: June 12, 2023
• Study Start: August 17, 2023
• Primary Completion: July 10, 2025
• Study Completion: December 12, 2025
• Last Updated: January 12, 2026

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)