A Study of Ferric Citrate to Improve Inflammation and Lipid Levels

End Stage Renal Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02661295
• Other study ID #: WUH 756275-1
• Status: Terminated
• Phase: Phase 4
• Start date: July 2015
• Est. completion date: March 15, 2018

Study information

• Verified date: March 2023
• Source: Winthrop University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 38
• Est. completion date: March 15, 2018
• Est. primary completion date: September 29, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Inflammation
• End Stage Renal Disease
• Hyperphosphatemia
• Inflammation
• Kidney Failure, Chronic

Intervention

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.

Locations

Country	Name	City	State
United States	Winthrop University Hospital	Mineola	New York

Sponsors (2)

Lead Sponsor	Collaborator
Winthrop University Hospital	Keryx Biopharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change in Total Cholesterol	Percent change in total cholesterol (mg/dl) from Baseline to Month 6.	Baseline, Month 6
Primary	Percent Change in LDL-Cholesterol	Percent change in low-density lipoprotein (LDL) cholesterol (mg/dl) from baseline to Month 6	Baseline, Month 6
Primary	Percent Change in HDL Cholesterol	Percent change in high-density lipoprotein (HDL) cholesterol (mg/dl) from baseline to Month 6.	Baseline, Month 6
Primary	Percent Change in Triglycerides	Percent change in triglycerides (mg/dl) from baseline to Month 6.	Baseline, Month 6
Primary	Percent Change in TNF-alpha	Percent change in tumor necrosis factor (TNF)-alpha (pg/ml) from Baseline to Month 6.	Baseline, Month 6
Primary	Percent Change in IL-6	Percent change in interleukin 6 (IL-6) (pg/ml) from baseline to Month 6	Baseline, Month 6
Primary	Percent Change in IL-8	Percent change in interleukin 8 (IL-8) (pg/ml) from baseline to Month 6.	Baseline, Month 6
Primary	Percent Change in Ferritin	Percent change in ferritin (ng/ml) from baseline to Month 6.	Baseline, Month 6
Primary	Percent Change in C-reactive Protein	Percent change in C-reactive Protein (mg/L) from baseline to Month 6.	Baseline, Month 6
Primary	Percent Change in Homocysteine	Percent change in homocysteine (micromol/L) from baseline to Month 6.	Baseline, Month 6
Primary	Change in Intravenous Iron Use	Change in intravenous iron use (mg) from Baseline to Month 6.	Baseline, Month 6
Secondary	Percent Change in Calcium	Percent change in calcium (mg/dL) from baseline to Month 6.	Baseline, Month 6
Secondary	Percent Change in Phosphorus	Percent change in phosphorus (md/dl) from baseline to Month 6.	Baseline, Month 6
Secondary	Percent Change in Parathyroid Hormone (PTH)	Percent change in PTH (pg/ml) from baseline to Month 6.	Baseline, Month 6