Safety of Furosemide in Premature Infants at Risk of Bronchopulmonary Dysplasia (BPD)

University of North Carolina (UNC)

Status and phase: Completed; Phase 2

Conditions: Bronchopulmonary Dysplasia

Treatments: Drug: Furosemide Cohort 2; Other: Placebo; Drug: Furosemide Cohort 3; Drug: Furosemide Cohort 1

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT02527798

HHSN27500033 (Other Grant/Funding Number)

5R01FD005101-02

15-1978

HHSN27500035 (Other Grant/Funding Number)

Details and patient eligibility

About

This study will describe the safety of furosemide in premature infants at risk of bronchopulmonary dysplasia and determine the preliminary effectiveness and pharmacokinetics (PK) of furosemide. Funding Source - FDA OOPD

Full description

Infants will receive a placebo or furosemide for 28 days. Blood samples will be collected for pharmacokinetic analysis.Premature infants will be randomized to receive placebo or furosemide in a dose escalating approach.

Follow up information will be collected up to 7 days after the last dose and at 36 weeks post menstrual age. The final study assessment will occur at the time of discharge, early termination or transfer.

Enrollment: 82 patients

Sex: All

Ages: 7 to 28 days old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Receiving positive airway pressure (nasal continuous airway pressure, nasal intermittent positive pressure ventilation, or nasal cannula flow > 1LPM) or mechanical ventilation (high frequency or conventional)
2. < 29 weeks gestational age at birth
3. 7-28 days postnatal age at time of first study dose

Exclusion criteria

1. Exposure to any diuretic ≤ 72 hours prior to first study dose
2. Previous enrollment and dosing in current study, "Safety of Furosemide in Premature Infants at Risk of Bronchopulmonary Dysplasia"
3. Hemodynamically significant patent ductus arteriosus, as determined by the investigator
4. Major congenital anomaly (e.g. congenital diaphragmatic hernia, congenital pulmonary adenomatoid malformation)
5. Meconium aspiration syndrome
6. Known allergy to any diuretic
7. Serum creatinine >1.7 mg/dL < 24 hours prior to first study dose
8. BUN >50 mg/dL < 24 hours prior to first study dose
9. Na <125 mmol/L < 24 hours prior to first study dose
10. K ≤2.5 mmol/L < 24 hours prior to first study dose
11. Ca ≤ 6 mg/dL < 24 hours prior to first study dose
12. Indirect bilirubin >10 mg/dL < 24 hours prior to first study dose
13. Any condition which would make the participant, in the opinion of the investigator, unsuitable for the study

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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82 participants in 6 patient groups, including a placebo group

Furosemide Cohort 1

Experimental group

Description:

Within cohort 1, infants will be randomized using a 3:1 scheme to receive furosemide or placebo. Those randomized to receive furosemide will receive (1mg/kg daily intravenously or 2 mg/kg daily enterally for 28 days.

Treatment:

Drug: Furosemide Cohort 1

Placebo Cohort 1

Placebo Comparator group

Description:

Infants randomized to the placebo treatment group will receive the equivalent volume of dextrose 5% for IV use or enteral use (if receiving enteral study drug).

Treatment:

Other: Placebo

Furosemide Cohort 2

Experimental group

Description:

Cohort 2 Infants will receive furosemide (1mg/kg every 6 hours intravenously or 2 mg/kg every 6 hours daily enterally) for 28 days.

Treatment:

Drug: Furosemide Cohort 2

Furosemide Cohort 3

Experimental group

Description:

Cohort 3 Infants will receive furosemide (2mg/kg every 6 hours intravenously or 4 mg/kg every 6 hours daily enterally) for 28 days.

Treatment:

Drug: Furosemide Cohort 3

Placebo Cohort 2

Placebo Comparator group

Description:

Infants randomized to the placebo treatment group will receive the equivalent volume of dextrose 5% for IV use or enteral use (if receiving enteral study drug).

Treatment:

Other: Placebo

Placebo Cohort 3

Placebo Comparator group

Description:

Infants randomized to the placebo treatment group will receive the equivalent volume of dextrose 5% for IV use or enteral use (if receiving enteral study drug).

Treatment:

Other: Placebo