Pragmatic Research on Diuretic Management in Early BPD Pilot

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

Interventions

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 8 days of total exposure to furosemide over the 16-day N-of-1 trial.

DRUG

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.

Sponsors & Collaborators

• Rainbow Babies and Children's Hospital

  collaborator OTHER

• Emory University

  collaborator OTHER

• RTI International

  collaborator OTHER

• National Heart, Lung, and Blood Institute (NHLBI)

  collaborator NIH

• Children's Hospital Medical Center, Cincinnati

  lead OTHER

Principal Investigators

• Heather Kaplan, MD, MSCE · Children's Hospital Medical Center, Cincinnati

• Anna Maria Hibbs, MD, MSCE · 1. Rainbow Babies and Children's Hospital

Study Design

Allocation

NA

Purpose

OTHER

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

2 Weeks

Max Age

10 Weeks

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-08-17

Primary Completion

2025-07-10

Completion

2025-12-12

FDA Drug

Yes

Countries

• United States

Study Locations