A Study of Ferric Citrate to Improve Inflammation and Lipid Levels

The Effect of Ferric Citrate on Inflammation and Lipid Levels in Patients on Hemodialysis

The risk of cardiovascular mortality in patients with end stage renal disease on hemodialysis is 10-100 times higher than the normal population. This is due in part to high levels of inflammation and vascular calcification found in these patients. Phosphate binders, particularly non-calcium based phosphate binders, may decrease cardiovascular risk by decreasing inflammation and vascular calcification. Ferric citrate a non-calcium based phosphate binder with approximately 210 mg of ferric iron has recently been approved for patients on hemodialysis. The effect of this phosphate binder on inflammation and lipid levels is unknown but investigators hypothesize that ferric citrate has the potential to improve inflammation and lipid levels in patients on hemodialysis by decreasing intravenous iron requirements and by improving lipid metabolism.

Study Overview

• Status: Terminated
• Conditions: End Stage Renal Disease; Chronic Inflammation; Hyperphosphatemia
• Intervention / Treatment: Drug: Ferric Citrate

Detailed Description

In patients with end stage renal disease (ESRD) receiving dialysis, the risk of cardiovascular death has been estimated to be 10-100 times higher than the general population without renal disease. This is due in part to high levels of inflammation and vascular calcification (large deposits of calcium in arteries) found in these patients. Chronic inflammation is particularly common in patients with ESRD. Parenteral iron therapy, which is common in patients on dialysis, may contribute to this inflammation and also a higher cardiovascular risk. Phosphate binders, particularly non-calcium based phosphate binders, may decrease cardiovascular risk by decreasing inflammation and vascular calcification. In a study of 10,044 hemodialysis patients, treatment with a phosphate binder was associated with improved survival. Ferric citrate a non-calcium based phosphate binder with approximately 210 mg of ferric iron has recently been approved for patients on hemodialysis. It has been shown to improve serum phosphorus levels and decrease intravenous iron requirements for patients on hemodialysis. The effect of this phosphate binder on inflammation and lipid levels is unknown but investigators hypothesize that ferric citrate has the potential to improve inflammation and lipid levels in patients on hemodialysis by decreasing intravenous iron requirements and by improving lipid metabolism.

Ferric citrate has the potential to decrease cardiovascular risk through multiple mechanisms:

1. acting as a non-calcium based binder to decrease serum phosphorus levels and vascular calcification,
2. decreasing intravenous iron requirements which in turn may decrease inflammation,
3. binding endotoxin (a harmful substance produced by microorganisms) in the gut and
4. improving lipid metabolism.

The purpose of this study is to examine the effect of ferric citrate on inflammatory markers and lipid levels.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Candace Grant, MD; Phone Number: 9054 516-663-0333; Email: cgrant@winthrop.org
• Study Contact Backup: Name: Shayan Shirazian, MD; Phone Number: 2170 516-663-0333; Email: sshirazian@winthrop.org

Study Locations

• United States
  • New York
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Hemodialysis treatment for ≥ 6 months
• Phosphate binder treatment for ≥ to 1 month
• Maintenance iron therapy with no more than 125mg IV iron weekly≥ to 1 month
• Serum phosphorus levels between 2.5 and 8 at screening
• Serum phosphorus ≥ to 6.0 mg/dL after a 2 week washout period.
• Serum ferritin ≥ 200 and < 600ng/ml after a 2 week washout period
• Serum calcium levels within normal range
• Predicted survival greater than 6 months

Exclusion Criteria:

• Intact PTH< 70 pg/ml or > 1,000 pg/ml
• Oral iron use
• Vitamin C supplement use
• Parathyroidectomy
• Active malignancy
• Hemodialysis via an intravenous catheter or arteriovenous (AV) graft
• Received > 250mg of IV iron over the two weeks prior to screening
• Whole blood transfusion within 3 months prior to screening
• Active bleeding other than from the dialysis access
• Hospitalization within one month prior to screening
• current infection
• Ongoing or uncontrolled inflammatory disorder
• Liver cirrhosis
• Likelihood of imminent renal transplantation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Ferric Citrate; Ferric citrate at a starting dose of 2 tablets with each meal will be given to all participants.	Drug: Ferric Citrate; Study participants will receive ferric citrate at a starting dose of 2 tablets with each meal if serum phosphorus levels are ≥ 6.0 mg/dL calcium levels are in the normal range, Tsat ≥ 20 and < 50% and ferritin ≥ 200 and < 500 ng/ml after a 2 week wash out period.; Other Names: Auryxia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Total Cholesterol	Percent change in total cholesterol (mg/dl) from Baseline to Month 6.	Baseline, Month 6
Percent Change in LDL-Cholesterol	Percent change in low-density lipoprotein (LDL) cholesterol (mg/dl) from baseline to Month 6	Baseline, Month 6
Percent Change in HDL Cholesterol	Percent change in high-density lipoprotein (HDL) cholesterol (mg/dl) from baseline to Month 6.	Baseline, Month 6
Percent Change in Triglycerides	Percent change in triglycerides (mg/dl) from baseline to Month 6.	Baseline, Month 6
Percent Change in TNF-alpha	Percent change in tumor necrosis factor (TNF)-alpha (pg/ml) from Baseline to Month 6.	Baseline, Month 6
Percent Change in IL-6	Percent change in interleukin 6 (IL-6) (pg/ml) from baseline to Month 6	Baseline, Month 6
Percent Change in IL-8	Percent change in interleukin 8 (IL-8) (pg/ml) from baseline to Month 6.	Baseline, Month 6
Percent Change in Ferritin	Percent change in ferritin (ng/ml) from baseline to Month 6.	Baseline, Month 6
Percent Change in C-reactive Protein	Percent change in C-reactive Protein (mg/L) from baseline to Month 6.	Baseline, Month 6
Percent Change in Homocysteine	Percent change in homocysteine (micromol/L) from baseline to Month 6.	Baseline, Month 6
Change in Intravenous Iron Use	Change in intravenous iron use (mg) from Baseline to Month 6.	Baseline, Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Calcium	Percent change in calcium (mg/dL) from baseline to Month 6.	Baseline, Month 6
Percent Change in Phosphorus	Percent change in phosphorus (md/dl) from baseline to Month 6.	Baseline, Month 6
Percent Change in Parathyroid Hormone (PTH)	Percent change in PTH (pg/ml) from baseline to Month 6.	Baseline, Month 6

Collaborators and Investigators

• Sponsor: Winthrop University Hospital
• Collaborators: Keryx Biopharmaceuticals
• Investigators: Principal Investigator: Candace Grant, MD, NYU Winthrop

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): September 29, 2017
• Study Completion (Actual): March 15, 2018

Study Registration Dates

• First Submitted: January 11, 2016
• First Submitted That Met QC Criteria: January 18, 2016
• First Posted (Estimate): January 22, 2016

Study Record Updates

• Last Update Posted (Actual): April 20, 2023
• Last Update Submitted That Met QC Criteria: March 30, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Kidney Diseases; Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Phosphorus Metabolism Disorders; Inflammation; Kidney Failure, Chronic; Hyperphosphatemia
• Other Study ID Numbers: WUH 756275-1