Fenoldopam to Prevent Renal Dysfunction in Indomethacin Treated Preterm Infants (Fenaki)

August 22, 2022 updated by: Jeffrey Segar, Medical College of Wisconsin
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 second to 4 weeks (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: 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.
Drug: 0.9%NS
Randomized to receive Fenoldopam or 0.9%NS
Other Names:
  • normal saline
Experimental: 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.
Drug: Fenoldopam
Randomized to receive Fenoldopam or 0.9%NS

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Changes in Urine Output (ml/kg/hr)
Time Frame: 66 hrs - from 6 hrs before beginning of fenoldopam or placebo infusion up to 24 hours after the last dose of indomethacin
Urine will be collected and measured in 6 hour increments beginning 6 hours prior to starting fenoldopam or placebo infusion. The first dose of indomethacin will be given 12 hours after starting fenoldopam or placebo. Two additional doses of indomethacin will be given 12 hours apart. Urine will continue to be collected and volume measured in 6 hour increments up to 24 hrs after the last dose of indomethacin. To summarize, urine will be collected and measured from time -6 hours to 0 hours. Fenoldapam or placebo will be initiated at time 0 hrs, indomethacin given at time 12, 24 and 36 hours, and urine collected and measured to time 60 hours.
66 hrs - from 6 hrs before beginning of fenoldopam or placebo infusion up to 24 hours after the last dose of indomethacin
Serum Levels of Fenoldopam During Infusion of the Drug and Following Discontinuation of the Drug Will be Measured by Liquid Chromatography and Mass Spectroscopy.
Time Frame: 60 hours
Blood samples for determination of serum fenoldopam levels will be obtained immediately prior to starting the infusion of fenoldopam (time 0 hour), continue through the 48 hour period of fenoldopam infusion and continue for an additional 12 hours after stopping the fenoldopam infusion.
60 hours
Change in Levels of Serum Albumin (mg/dl)
Time Frame: 48 hrs
Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period
48 hrs
Changes in Serum Creatinine (mg/dl)
Time Frame: 48 hours
Serum creatinine will be measured immediately prior to first dose of indomethacin, immediately prior to the third dose of indomethacin (24 hr later) and 24 hours after the third dose of indomethacin
48 hours
Serum Levels of Fenoldopam Will be Related the Changes in Urine Volume
Time Frame: 60 hours
We will relate serum levels of fenoldopam to changes in urine volume over the duration of time of fenoldopam infusion and after discontinuation of infusion. This constitutes part of the pharmacodynamic analysis
60 hours
Serum Levels of Fenoldopam Will be Related to Absolute and Relative Changes in Serum Creatinine
Time Frame: 60 hours
We will relate serum levels of fenoldopam to serum creatinine values over the duration of time of fenoldopam infusion and after discontinuation of infusion. This constitutes part of the pharmacodynamic analysis
60 hours
Change in Levels of Serum Beta 2 Macroglobulin (mcg/ml)
Time Frame: 48 hrs
Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period
48 hrs
Change in Levels of Serum Cystatin C (mcg/ml)
Time Frame: 48 hrs
Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period
48 hrs
Change in Levels of Serum Epidermal Growth Factor (EGF) (ng/ml)
Time Frame: 48 hrs
Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period
48 hrs
Change in Levels of Serum Osteopontin (ng/ml)
Time Frame: 48 hrs
Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period
48 hrs
Change in Levels of Serum Uromodulin (mg/dl)
Time Frame: 48 hrs
Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period
48 hrs
Change in Level of Urine Albumin (mg/dl)
Time Frame: 48 hr
Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period
48 hr
Change in Level of Urine Beta 2 Macroglobulin (mcg/ml)
Time Frame: 48 hrs
Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period
48 hrs
Change in Level of Urine Cystatin C (mcg/ml)
Time Frame: 48 hr
Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period
48 hr
Change in Levels of Urine Epidermal Growth Factor (EGF) (ng/ml)
Time Frame: 48 hr
Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period
48 hr
Change in Levels of Urine Osteopontin (ng/ml)
Time Frame: 48 hrs
Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period
48 hrs
Change in Levels of Urine Uromodulin (mg/dl)
Time Frame: 48 hrs
Period from just prior to first dose of indomethacin (time point 12 hours) to 24 hours beyond last dose of indomethacin ( which is time point 60 hours). Thus, this aspect of study takes place between time point 12 hr and time point 60 hr, which is a 48 hour period
48 hrs

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Medical College of Wisconsin

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jeffrey Segar, MD, University of Iowa

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 6, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 31, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 31, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 27, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 30, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 3, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 16, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 22, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DK113073-01A1

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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