Ferric Citrate for the Prevention of Renal Failure in Adults With Advanced Chronic Kidney Disease (FRONTIER)

August 11, 2025 updated by: USRC Kidney Research

Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Determine the Effect of Ferric Citrate on Time to a Composite Endpoint of Initiation of Maintenance Dialysis or All-cause Mortality vs Placebo in Adults With Advanced CKD

A 9-month randomized, double-blind, placebo-controlled study to compare the effect of fixed dose ferric citrate versus placebo in patients with advanced chronic kidney disease (eGFR ≤20 ml/min/1.73m2) on the composite endpoint of time to initiation of maintenance dialysis or all-cause mortality.

Study Overview

Status

Status

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

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

This multicenter, randomized, double-blind, placebo-controlled clinical trial is being conducted to determine the effect of ferric citrate on the time to a composite endpoint of initiation of maintenance dialysis or all-cause mortality in patients with non-dialysis dependent, advanced CKD. Up to 400 subjects will be randomized in 1:1 ratio to receive either ferric citrate or matching placebo. All subjects will initiate dosing at 2 tablets per meal or snacks, up to 3 times per day (maximum of 6 tablets per day). The dose of ferric citrate/placebo will only be adjusted based on safety and/or tolerability. Given the double-blind design of this trial, investigators will be instructed to not prescribe commercial Auryxia to either study arm. Study visits during the treatment period are to be conducted as part of routine scheduled clinical encounters. Standard of care local laboratory results will be collected however no study specific laboratory tests other than a pregnancy test in women of child-bearing potential will be required.

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.
289

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 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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Arkansas
      • Pine Bluff, Arkansas, United States, 71603
        • Arkansas Nephrology & Hypertension Clinic
    • California
      • Chula Vista, California, United States, 91910
        • Balboa Research SMO
      • El Centro, California, United States, 92243
        • Balboa Research SMO
      • Escondido, California, United States, 92025
        • Balboa Research SMO
      • La Mesa, California, United States, 91942
        • Balboa Research SMO
      • San Diego, California, United States, 92111
        • Balboa Research SMO - Kearney Mesa
    • Colorado
      • Lone Tree, Colorado, United States, 80124
        • Rocky Mountain Kidney Care
    • Florida
      • Fort Myers, Florida, United States, 33908
        • Associates in Nephrology
    • Georgia
      • Albany, Georgia, United States, 31701
        • Dialysis Clinic, Inc.
      • Dalton, Georgia, United States, 30720
        • Nephrology and Hypertension Specialists, PC
    • Indiana
      • Shelbyville, Indiana, United States, 46176
        • Major Health Partners
    • Missouri
      • Kansas City, Missouri, United States, 64131
        • Kidney Associates of Kansas City
    • New Jersey
      • South River, New Jersey, United States, 08882
        • Nephrology-Hypertension Associates of Central NJ
    • New Mexico
      • Gallup, New Mexico, United States, 87301
        • High Desert Nephrology Associates
    • New York
      • Amherst, New York, United States, 14228
        • Nephrology Associates of Western NY
    • South Carolina
      • Spartanburg, South Carolina, United States, 29302
        • Spartanburg Nephrology Associates
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • Dialysis Clinic, Inc.
    • Texas
      • Live Oak, Texas, United States, 78233
        • South Texas Renal Care Group
      • San Antonio, Texas, United States, 78212
        • Clinical Advancement Center, PLLC
      • San Antonio, Texas, United States, 78202
        • South Texas Renal Care Group
      • San Antonio, Texas, United States, 78211
        • South Texas Renal Care Group
      • San Antonio, Texas, United States, 78221
        • South Texas Renal Care Group
      • San Antonio, Texas, United States, 78251
        • South Texas Renal Care Group

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Adult patients greater or equal to 18 years old.
  2. Diagnosis of NDD advanced CKD, regardless of etiology. Advanced CKD is defined as at least one local laboratory determined estimated glomerular filtration rate (eGFR) ≤20 ml/min/1.73m2 (calculated per any commonly used method or equation for estimating eGFR) within 90 days of Day 1.
  3. Most recent transferrin saturation (TSAT) less than or equal to 45% within 45 days of Day 1.
  4. Most recent serum phosphate is greater or equal to 3.0 mg per dL within 45 days of Day 1.
  5. Most recent ferritin is less than or equal to 500 ng per mL within 45 days of Day 1.
  6. Women of child-bearing potential must have a negative serum or urine pregnancy test within 28 days prior to Day 1.
  7. Understands the procedures and requirements of the study and provides written informed consent and authorization for protected health information disclosure.

Exclusion Criteria:

  1. Patients who, in the opinion of the Investigator, have acute kidney injury rather than CKD.
  2. Patients with planned/imminent maintenance dialysis, or that are anticipated to begin maintenance dialysis within 8 weeks from Screening, in the opinion of the Investigator.
  3. A known allergy or intolerance to ferric citrate or any of its constituents.
  4. Hypersensitivity reaction to previous oral iron therapy.
  5. History of hemochromatosis or iron overload syndrome (e.g., hereditary sideroblastic anemia, thalassemia, polycythemia vera).
  6. Active malignancy requiring current treatment except for non-melanoma skin cancer regardless of treatment.
  7. Active drug or alcohol dependence or abuse (excluding tobacco use or use of medical or recreational marijuana) within the 12 months prior to Screening or evidence of such abuse, in the opinion of the Investigator.
  8. Limited life expectancy (less than 6 months) in the opinion of the Investigator.
  9. Females who are known to be pregnant or are breast-feeding during Screening or are planning to become pregnant and breastfeeding during the study period.
  10. Evidence of a clinically active infection requiring antibiotics at Randomization.
  11. Unable to comply with study requirements or in the opinion of the Investigator, not clinically stable to participate in the study.
  12. Use of an investigational medication or participation in an investigational study within 30 days prior to Day 1.
  13. Patients with a scheduled date for receipt of living donor kidney transplant

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: Treatment
  • 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.
Experimental: Ferric citrate
Supplied as tablets for oral administration containing 1 gram ferric citrate (210 milligrams of ferric iron). Administered orally with meals or snacks.
Drug: Ferric Citrate 1 GM Oral Tablet [AURYXIA]
All subjects will be instructed to take study drug (ferric citrate or placebo) at a fixed dose of 2 tablets per meal or snacks, up to three times per day. The maximum dose is 6 tablets per day. No additional tablets (beyond a total of 6 per day) should be taken. Tablets should not be crushed or chewed.
Other Names:
  • Auryxia
Placebo Comparator: Placebo
Tablets, matching in color and size to ferric citrate.
Drug: Placebo
All subjects will be instructed to take study drug (ferric citrate or placebo) at a fixed dose of 2 tablets per meal or snacks, up to three times per day. The maximum dose is 6 tablets per day. No additional tablets (beyond a total of 6 per day) should be taken. Tablets should not be crushed or chewed.

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
Number of Participants Achieving a Composite Endpoint of Initiation of Maintenance Dialysis or All-cause Mortality
Time Frame: 9 months
Number of participants achieving a composite endpoint of initiation of maintenance dialysis or all-cause mortality
9 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Hospitalization Events Reported as a Serious Adverse Event (SAE) (Excluding Disease-related Hospitalization [e.g., Dialysis Access Placement, Dialysis Initiation, Kidney Transplant] and Elective Procedures)
Time Frame: 9 months
Number of hospitalization events reported as a serious adverse event (SAE) (excluding disease-related hospitalization [e.g., dialysis access placement, dialysis initiation, kidney transplant] and elective procedures)
9 months
Component of Primary - Initiation of Maintenance Dialysis
Time Frame: 9 months
Component of Primary - Number of participants initiating maintenance dialysis
9 months
Component of Primary - All-Cause Mortality
Time Frame: 9 months
Component of Primary - Number of patients reaching endpoint of all-cause mortality.
9 months

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.
USRC Kidney Research

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Akebia Therapeutics

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: Geoff Block, MD, USRC Kidney Research

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.
March 30, 2022

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 24, 2024

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 24, 2024

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 6, 2021

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.
October 6, 2021

First Posted (Actual)

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.
October 20, 2021

Study Record Updates

Last Update Posted (Estimated)

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.
August 29, 2025

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 11, 2025

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.
April 1, 2025

More Information

Terms related to this study

Keywords

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.
  • USRC-2021-002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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