Fenoldopam to Prevent Renal Dysfunction in Indomethacin Treated Preterm Infants

NCT ID: NCT02620761

Last Updated: 2022-09-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-06
• Study Completion Date: 2020-01-31

Brief Summary

The investigators will conduct a prospective, blinded, randomized, placebo-controlled trial with a sample size of 20 patients in each of the two arms (fenoldopam vs placebo) based upon a difference in serum creatinine by one standard deviation. Fluid and salt intake will be held constant within clinical parameters and carefully measured. Fenoldopam will be started at 0.1 ug/kg/min. If, after 6 hrs there is no decrease in blood pressure, the dose will be increased to 0.2 ug/kg/min. This dose will be continued throughout the remainder of the study. A study of pediatric patients previously provided to the FDA showed no hypotension at a dose of 0.2 ug/kg/min. Fenoldopam will be started 12 hrs before the first dose of indomethacin and discontinued 12 hrs after the 3rd dose of indomethacin. Study samples will include both blood and urine. The primary outcome will be a reduction in renal dysfunction, as determined by creatinine and urine output over the course of treatment. Additional outcomes will include determination of known and novel metabolomic urine markers of renal dysfunction.

Detailed Description

Hypotheses

• The investigators primary hypothesis is that fenoldopam reduces renal dysfunction associated with indomethacin administration for closure of patent ductus arteriosus in preterm infants. A secondary endpoint or measured outcome will be the determination of fenoldopam pharmacokinetics in the premature population. Lastly, the investigators hypothesize that urine and serum acute kidney injury (AKI) biomarkers will be superior to contemporary neonatal AKI definitions in their ability to identify renal injury.

Specific Aims

• Evaluate the effect of fenoldopam on renal function in preterm infants administered indomethacin
• Determination of fenoldopam pharmacokinetic and pharmacodynamic profiles in preterm infants
• Define whether newly identified biomarkers of renal dysfunction are more sensitive markers of renal dysfunction following indomethacin than traditional markers including urine output and serum creatinine.

Study design

• The study will be a prospective, blinded, randomized, placebo controlled trial. Fenoldopam will be started at 0.1 ug/kg/min. If, after 6 hrs there is no decrease in blood pressure, the dose will be increased to 0.2 ug/kg/min and continued throughout the remainder of the study. The previous study in pediatric patients showed no hypotension at a dose of 0.2 ug/kg/min. Fenoldopam will be started 12 hrs before the first dose of indomethacin and discontinued 12 hrs after the 3rd dose of indomethacin.

Describe study population or sample material

• preterm infants born at less than or equal to 28 weeks gestation with patent ductus arteriosus in whom attempted medical closure with indomethacin is indicated as decided upon by the attending physician Sample size/power of primary endpoint
• Sample size is 20 patients in each of the two arms (fenoldopam vs placebo) based upon an improvement in serum creatinine by one standard deviation.

Conditions

Patent Ductus Arteriosus (PDA); Acute Kidney Injury (AKI)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Control

Infants in the Placebo arm will receive 0.9% sodium chloride (0.1 ml/hr). If, after 6 hrs there is not a clinically concerning decrease in blood pressure, as determined by attending physician, the rate of infusion (in this arm the placebo) will be increased to 0.2 ml/kg/hr. This rate will be continued throughout the remainder of the study.

Group Type: PLACEBO_COMPARATOR

0.9%NS

Intervention Type: DRUG

Randomized to receive Fenoldopam or 0.9%NS

Fenoldopam

Infants in the experimental arm will receive fenoldopam (60 ug/ml; 0.1 ml/hr to provide 0.1ug/kg/min). If, after 6 hrs there is not a clinically concerning decrease in blood pressure, as determined by attending physician, the rate of infusion will be increased to 0.2 ml/kg/hr (0.2 ug/kg/min for infants receiving fenoldopam). This rate will be continued throughout the remainder of the study.

Group Type: EXPERIMENTAL

Fenoldopam

Intervention Type: DRUG

Randomized to receive Fenoldopam or 0.9%NS

Interventions

Fenoldopam

Randomized to receive Fenoldopam or 0.9%NS

Intervention Type: DRUG

0.9%NS

Randomized to receive Fenoldopam or 0.9%NS

Intervention Type: DRUG

Other Intervention Names

normal saline

Eligibility Criteria

Inclusion Criteria

1. Gestational age at birth 23 0/7 to 27 6/7 weeks by best obstetrical dating

2. No previous exposure to indomethacin

3. Clinical determination to use indomethacin to attempt closure of PDA

4. No known congenital abnormalities involving the kidneys, heart or lungs

5. No preexisting renal dysfunction, defined as serum creatinine > 1.0 mg/dl, or urine output <1.0 ml/kg/hour over the previous 24 hours.

Exclusion Criteria

1. Enrollment in concurrent study in which interventions may contribute confounding variables or have competing outcomes

2. Infants with antenatally or postnatally diagnosed renal or urinary tract abnormalities

3. Infants with umbilical cord or infant blood pH below 7.0 at any time before enrollment

4. Attending physician unwilling to have infant participate in study

5. Absence of informed consent

• Minimum Eligible Age: 0 Days
• Maximum Eligible Age: 28 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical College of Wisconsin

OTHER

Sponsor Role: lead

Responsible Party

Jeffrey Segar

Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeffrey Segar, MD

Role: PRINCIPAL_INVESTIGATOR

University of Iowa

Locations

University of Iowa

Iowa City, Iowa, United States

Countries

United States

References

Esezobor CI, Bhatt GC, Effa EE, Hodson EM. Fenoldopam for preventing and treating acute kidney injury. Cochrane Database Syst Rev. 2024 Nov 28;11(11):CD012905. doi: 10.1002/14651858.CD012905.pub2.

Reference Type: DERIVED

PMID: 39607014 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

DK113073-01A1

Identifier Type: -

Identifier Source: org_study_id