Clinical trial NCT05898022: Pragmatic Research on Diuretic Management in Early BPD Pilot
Official title: Pragmatic Research on Diuretic Management in Early Bronchopulmonary Dysplasia (PRIMED) Pilot Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Bronchopulmonary Dysplasia
Keywords: furosemide
ventilator-induced lung injury
lung injury
lung diseases
respiratory tract diseases
infant
premature diseases
newborn
diseases
diuretics
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
Collaborators: name: Rainbow Babies and Children's Hospital
name: Emory University
name: RTI International
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2023-06-12
Enrollment: 30
Sex: ALL
Minimum age (years): 2
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: OTHER

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?


Eligibility criteria: 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

Primary outcomes:
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
timeFrame: 23 Days
measure: Percent of providers willing to support randomizing a responder infant
timeFrame: 30 Days
Secondary outcomes:
measure: Percent of enrolled infants completing full N-of-1 trial and identified as responder
timeFrame: 23 days
measure: Percent of enrolled infants completing full N-of-1 trial
timeFrame: 23 days
measure: Percent of enrolled infants on respiratory support at the conclusion of the N-of-1 trial
timeFrame: 23 days
measure: Percent of parents willing to randomize responder infant
timeFrame: 30 days
measure: Rate of chronic diuretic use among responders (and non-responders)
timeFrame: 30 days
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Durham
country: United States
facility: RTI International
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University, Rainbow Babies and Children's Hospital
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Heather Kaplan, MD, MSCE
role: PRINCIPAL_INVESTIGATOR
affiliation: 1. Rainbow Babies and Children's Hospital
name: Anna Maria Hibbs, MD, MSCE
role: PRINCIPAL_INVESTIGATOR
References: