30 Participants Needed

Diuretic Therapy for Bronchopulmonary Dysplasia

(PRIMED Trial)

Recruiting at 3 trial locations
HK
AM
Overseen ByAnna Maria C. Hibbs, MD, MSCE
Age: < 18
Sex: Any
Trial Phase: Phase 4
Sponsor: Children's Hospital Medical Center, Cincinnati
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 5 JurisdictionsThis treatment is already approved in other countries

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants stop taking any longer-acting diuretics at least 5 days before enrollment. If you are currently on chronic diuretics, you will need to stop those as well. However, treatment with chronic steroids for adrenal insufficiency or cardiovascular instability is allowed.

What data supports the effectiveness of the drug Furosemide for treating bronchopulmonary dysplasia?

Research shows that diuretics like Furosemide are often used in infants with bronchopulmonary dysplasia to improve lung function, although the evidence supporting their effectiveness is limited and mixed. Some studies suggest potential benefits in pulmonary outcomes, but they also highlight concerns about side effects like poor weight gain.12345

Is furosemide safe for humans?

Research shows that furosemide, often used in premature infants for conditions like bronchopulmonary dysplasia, has been studied for safety. It is generally considered safe, but like any medication, it may have side effects, especially in vulnerable populations like preterm infants.26789

How is the drug Furosemide unique in treating bronchopulmonary dysplasia?

Furosemide is unique in treating bronchopulmonary dysplasia because it can be inhaled, which may improve lung function without causing the side effects associated with its traditional use as an injected diuretic, such as low potassium levels and bone issues.123910

What is the purpose of this trial?

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?

Research Team

AM

Anna Maria C. Hibbs, MD, MSCE

Principal Investigator

1. Rainbow Babies and Children's Hospital

HK

Heather Kaplan, MD, MSCE

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Eligibility Criteria

This trial is for premature babies with a lung condition called bronchopulmonary dysplasia (BPD), who are expected to be hospitalized for at least 28 days, can eat enough, need extra oxygen, and were born before the 28th week of pregnancy. Babies on certain steroids or diuretics recently, those with specific blood test results or major birth defects aren't eligible.

Inclusion Criteria

<28 weeks gestation at birth
My baby was born between 29 and 32 weeks of pregnancy.
I need help breathing with a machine and high oxygen levels.
See 2 more

Exclusion Criteria

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
I haven't taken long-acting diuretics like hydrochlorothiazide in the last 5 days.
I am currently prescribed and taking diuretics regularly.
See 2 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

N-of-1 Trial

Each individual N-of-1 trial will have 2 blocks where patients crossover between furosemide and placebo to determine short-term response

4 weeks
Multiple visits as per crossover design

Follow-up

Participants are monitored for safety and effectiveness after the N-of-1 trial

4 weeks

Treatment Details

Interventions

  • Furosemide
  • Placebo
Trial Overview The PRIMED study tests if furosemide helps babies with BPD by comparing it against a placebo in an N-of-1 trial design. This means each baby will receive both the real medicine and a fake one at different times to see which works better for them individually.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: N-of-1 TrialExperimental Treatment2 Interventions
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.

Furosemide is already approved in European Union, United States, Canada, Japan, China for the following indications:

🇪🇺
Approved in European Union as Lasix for:
  • Hypertension
  • Edema associated with congestive heart failure
  • Liver cirrhosis
  • Renal disease
  • Nephrotic syndrome
🇺🇸
Approved in United States as Lasix for:
  • Edema associated with congestive heart failure
  • Liver cirrhosis
  • Renal disease
  • Nephrotic syndrome
  • Acute pulmonary edema
🇨🇦
Approved in Canada as Lasix for:
  • Edema associated with congestive heart failure
  • Liver cirrhosis
  • Renal disease
  • Nephrotic syndrome
  • Hypertension
🇯🇵
Approved in Japan as Lasix for:
  • Edema associated with congestive heart failure
  • Liver cirrhosis
  • Renal disease
  • Nephrotic syndrome
🇨🇳
Approved in China as Lasix for:
  • Edema associated with congestive heart failure
  • Liver cirrhosis
  • Renal disease
  • Nephrotic syndrome
  • Hypertension

Find a Clinic Near You

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials
844
Recruited
6,566,000+

Rainbow Babies and Children's Hospital

Collaborator

Trials
9
Recruited
4,000+

Emory University

Collaborator

Trials
1,735
Recruited
2,605,000+

RTI International

Collaborator

Trials
201
Recruited
942,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials
3,987
Recruited
47,860,000+

Findings from Research

Long-term oral diuretic therapy with spironolactone and chlorothiazide significantly improved pulmonary function in preterm infants with bronchopulmonary dysplasia, showing a 46% increase in dynamic pulmonary compliance and a 31% decrease in airway resistance during treatment.
While the diuretic group required less supplemental oxygen compared to the placebo group after 4 weeks, the overall duration of oxygen requirement did not differ between the two groups, and the pulmonary function improvements were not sustained after discontinuation of the diuretics.
Randomized trial of long-term diuretic therapy for infants with oxygen-dependent bronchopulmonary dysplasia.Kao, LC., Durand, DJ., McCrea, RC., et al.[2022]
Inhaled furosemide at doses of 1 and 2 mg/kg has shown to improve pulmonary function in preterm neonates with acute respiratory distress and potential bronchopulmonary dysplasia, without significant adverse effects.
Current studies only evaluated the effects of a single dose and monitored outcomes for a short duration (2 to 4 hours), indicating a need for further research to establish optimal dosing and long-term safety.
Aerosolized furosemide in the treatment of acute respiratory distress and possible bronchopulmonary dysplasia in preterm neonates.Pai, VB., Nahata, MC.[2017]
A survey of pediatric pulmonologists and neonatologists in Israel revealed significant variability in diuretic weaning strategies for outpatient preterm infants with bronchopulmonary dysplasia (BPD), indicating a lack of consensus in clinical practice.
Most healthcare providers expressed dissatisfaction with the current guidelines and data on diuretic use in BPD, highlighting the need for more research, including a larger controlled study to compare gradual tapering versus immediate discontinuation of diuretics.
Weaning Strategy of Diuretics in Outpatient Preterm Infants with Bronchopulmonary Dysplasia: A National Survey.Armoni Domany, K., Amirav, I., Sadot, E., et al.[2022]

References

Randomized trial of long-term diuretic therapy for infants with oxygen-dependent bronchopulmonary dysplasia. [2022]
Aerosolized furosemide in the treatment of acute respiratory distress and possible bronchopulmonary dysplasia in preterm neonates. [2017]
Weaning Strategy of Diuretics in Outpatient Preterm Infants with Bronchopulmonary Dysplasia: A National Survey. [2022]
Postnatal diuretics, weight gain and home oxygen requirement in extremely preterm infants. [2023]
Diuretic Tolerance to Repeated-dose Furosemide in Infants Born Very Preterm with Bronchopulmonary Dysplasia. [2023]
Furosemide Exposure and Prevention of Bronchopulmonary Dysplasia in Premature Infants. [2023]
Nebulized furosemide in the treatment of bronchopulmonary dysplasia in preterm infants. [2021]
The association between diuretic class exposures and enteral electrolyte use in infants developing grade 2 or 3 bronchopulmonary dysplasia in United States children's hospitals. [2023]
Diuretic exposure in premature infants from 1997 to 2011. [2023]
10.United Statespubmed.ncbi.nlm.nih.gov
Pulmonary effect of inhaled furosemide in ventilated infants with severe bronchopulmonary dysplasia. [2019]
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