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Pragmatic Research on Diuretic Management in Early BPD Pilot

Phase 4
Recruiting
Conditions
Bronchopulmonary Dysplasia
Interventions
Drug: Placebo (plus placebo electrolyte solution)
Registration Number
NCT05898022
Lead Sponsor
Children's Hospital Medical Center, Cincinnati
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?

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
30
Inclusion Criteria
  1. <28 weeks gestation at birth
  2. Post-Menstrual Age (PMA) of 29-32 weeks gestation
  3. 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%.
  4. Receiving enteral feedings of 120 mL/kg/day or greater
  5. Expected to be hospitalized for at least 28 days after enrollment
Exclusion Criteria
  1. Major congenital anomalies (e.g., known renal anomalies, congenital heart disease, congenital diaphragmatic hernia, or chromosomal anomalies)
  2. 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.
  3. 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.
  4. 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
  5. Active order for standing, regularly scheduled diuretics (e.g., chronic diuretics)
  6. Non-English speaking
  7. Current treatment with ibuprofen or indocin

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
N-of-1 TrialFurosemide (plus potassium chloride)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.
N-of-1 TrialPlacebo (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.
Primary Outcome Measures
NameTimeMethod
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 responder23 Days
Percent of providers willing to support randomizing a responder infant30 Days
Secondary Outcome Measures
NameTimeMethod
Percent of enrolled infants completing full N-of-1 trial and identified as responder23 days
Percent of enrolled infants completing full N-of-1 trial23 days
Percent of enrolled infants on respiratory support at the conclusion of the N-of-1 trial23 days
Percent of parents willing to randomize responder infant30 days
Rate of chronic diuretic use among responders (and non-responders)30 days

Trial Locations

Locations (4)

Cincinnati Children's Hospital Medical Center

🇺🇸

Cincinnati, Ohio, United States

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

🇺🇸

Cleveland, Ohio, United States

RTI International

🇺🇸

Durham, North Carolina, United States

Emory University

🇺🇸

Atlanta, Georgia, United States

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