Pragmatic Research on Diuretic Management in Early BPD Pilot

Bronchopulmonary Dysplasia Clinical Trial

— PRIMED  

Official title:

Pragmatic Research on Diuretic Management in Early Bronchopulmonary Dysplasia (PRIMED) Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05898022
• Other study ID #: 2021-0120
• Secondary ID: R34HL158586-01A1
• Status: Recruiting
• Phase: Phase 4
• Start date: August 17, 2023
• Est. completion date: September 30, 2025

Study information

• Verified date: January 2024
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: Heather Kaplan, MD, MSCE
• Phone: 513-803-0478
• Email: heather.kaplan[@]cchmc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical 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). 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?

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: September 30, 2025
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Weeks to 10 Weeks

Eligibility

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 and FiO2 = 25% or requiring non-invasive positive pressure respiratory support (NCPAP= 5 cm H20, NIPPV/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. Serum creatinine > 1.7 mg/dL, BUN >50 mg/dL, Na <125 mmoL/L, K = 2.5 mmol/L, or Ca = 6 mg/dL in week prior to enrollment

3. Treatment with a time-limited course of Dexamethasone or hydrocortisone within 10 days of enrollment. Exposure to a time-limited course dexamethasone or hydrocortisone for respiratory failure within 10 days of enrollment may result in carryover effects that confound the N-of-1 trial. Treatment with chronic steroids for adrenal insufficiency is not an exclusion criteria.

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

Related Conditions & MeSH terms

• Bronchopulmonary Dysplasia

Intervention

Drug:
• 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 14 days of total exposure to furosemide over the 28-day 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.

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	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

Sponsors (5)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati	Emory University, National Heart, Lung, and Blood Institute (NHLBI), Rainbow Babies and Children's Hospital, RTI International

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		35 Days
Primary	Percent of providers willing to support randomizing a responder infant		42 Days
Secondary	Percent of enrolled infants completing full N-of-1 trial and identified as responder		35 days
Secondary	Percent of enrolled infants completing full N-of-1 trial		35 days
Secondary	Percent of enrolled infants on respiratory support at the conclusion of the N-of-1 trial		35 days
Secondary	Percent of parents willing to randomize responder infant		42 days
Secondary	Rate of chronic diuretic use among responders (and non-responders)		42 days