A Study of Ferric Citrate to Improve Inflammation and Lipid Levels
Primary Purpose
End Stage Renal Disease, Hyperphosphatemia, Chronic Inflammation
Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Ferric Citrate
Sponsored by
About this trial
This is an interventional other trial for End Stage Renal Disease
Eligibility Criteria
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
Sites / Locations
- Winthrop University Hospital
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Ferric Citrate
Arm Description
Ferric citrate at a starting dose of 2 tablets with each meal will be given to all participants.
Outcomes
Primary Outcome Measures
Percent Change in Total Cholesterol
Percent change in total cholesterol (mg/dl) from Baseline to Month 6.
Percent Change in LDL-Cholesterol
Percent change in low-density lipoprotein (LDL) cholesterol (mg/dl) from baseline to Month 6
Percent Change in HDL Cholesterol
Percent change in high-density lipoprotein (HDL) cholesterol (mg/dl) from baseline to Month 6.
Percent Change in Triglycerides
Percent change in triglycerides (mg/dl) from baseline to Month 6.
Percent Change in TNF-alpha
Percent change in tumor necrosis factor (TNF)-alpha (pg/ml) from Baseline to Month 6.
Percent Change in IL-6
Percent change in interleukin 6 (IL-6) (pg/ml) from baseline to Month 6
Percent Change in IL-8
Percent change in interleukin 8 (IL-8) (pg/ml) from baseline to Month 6.
Percent Change in Ferritin
Percent change in ferritin (ng/ml) from baseline to Month 6.
Percent Change in C-reactive Protein
Percent change in C-reactive Protein (mg/L) from baseline to Month 6.
Percent Change in Homocysteine
Percent change in homocysteine (micromol/L) from baseline to Month 6.
Change in Intravenous Iron Use
Change in intravenous iron use (mg) from Baseline to Month 6.
Secondary Outcome Measures
Percent Change in Calcium
Percent change in calcium (mg/dL) from baseline to Month 6.
Percent Change in Phosphorus
Percent change in phosphorus (md/dl) from baseline to Month 6.
Percent Change in Parathyroid Hormone (PTH)
Percent change in PTH (pg/ml) from baseline to Month 6.
Full Information
NCT ID
NCT02661295
First Posted
January 11, 2016
Last Updated
March 30, 2023
Sponsor
Winthrop University Hospital
Collaborators
Keryx Biopharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT02661295
Brief Title
A Study of Ferric Citrate to Improve Inflammation and Lipid Levels
Official Title
The Effect of Ferric Citrate on Inflammation and Lipid Levels in Patients on Hemodialysis
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Terminated
Why Stopped
38 enrolled, 19 completed the study when loss of funding occurred
Study Start Date
July 2015 (undefined)
Primary Completion Date
September 29, 2017 (Actual)
Study Completion Date
March 15, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Winthrop University Hospital
Collaborators
Keryx Biopharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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.
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:
acting as a non-calcium based binder to decrease serum phosphorus levels and vascular calcification,
decreasing intravenous iron requirements which in turn may decrease inflammation,
binding endotoxin (a harmful substance produced by microorganisms) in the gut and
improving lipid metabolism.
The purpose of this study is to examine the effect of ferric citrate on inflammatory markers and lipid levels.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
End Stage Renal Disease, Hyperphosphatemia, Chronic Inflammation
7. Study Design
Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Model Description
This study will be designed as a single arm, prospective, experimental trial of 45 hemodialysis patients. Patients on hemodialysis at least 6 months and receiving a phosphate binder with serum phosphorus levels between 2.5 and 8.0 mg/dL, normal serum calcium levels, and on maintenance iron therapy are potentially eligible. Participants will receive ferric citrate after at least a 2 week washout period from previous phosphate binders if phosphorus is ≥ 5.5 mg/dl, calcium is within the normal range and ferritin ≥ 200 and < 600 ng/ml. Ferric citrate will be titrated to maintain serum phosphorus and calcium within acceptable levels. Inflammatory markers and lipid levels will be tested at 0, 3, and 6 months.
Masking
None (Open Label)
Allocation
N/A
Enrollment
38 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ferric Citrate
Arm Type
Other
Arm Description
Ferric citrate at a starting dose of 2 tablets with each meal will be given to all participants.
Intervention Type
Drug
Intervention Name(s)
Ferric Citrate
Other Intervention Name(s)
Auryxia
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percent Change in Total Cholesterol
Description
Percent change in total cholesterol (mg/dl) from Baseline to Month 6.
Time Frame
Baseline, Month 6
Title
Percent Change in LDL-Cholesterol
Description
Percent change in low-density lipoprotein (LDL) cholesterol (mg/dl) from baseline to Month 6
Time Frame
Baseline, Month 6
Title
Percent Change in HDL Cholesterol
Description
Percent change in high-density lipoprotein (HDL) cholesterol (mg/dl) from baseline to Month 6.
Time Frame
Baseline, Month 6
Title
Percent Change in Triglycerides
Description
Percent change in triglycerides (mg/dl) from baseline to Month 6.
Time Frame
Baseline, Month 6
Title
Percent Change in TNF-alpha
Description
Percent change in tumor necrosis factor (TNF)-alpha (pg/ml) from Baseline to Month 6.
Time Frame
Baseline, Month 6
Title
Percent Change in IL-6
Description
Percent change in interleukin 6 (IL-6) (pg/ml) from baseline to Month 6
Time Frame
Baseline, Month 6
Title
Percent Change in IL-8
Description
Percent change in interleukin 8 (IL-8) (pg/ml) from baseline to Month 6.
Time Frame
Baseline, Month 6
Title
Percent Change in Ferritin
Description
Percent change in ferritin (ng/ml) from baseline to Month 6.
Time Frame
Baseline, Month 6
Title
Percent Change in C-reactive Protein
Description
Percent change in C-reactive Protein (mg/L) from baseline to Month 6.
Time Frame
Baseline, Month 6
Title
Percent Change in Homocysteine
Description
Percent change in homocysteine (micromol/L) from baseline to Month 6.
Time Frame
Baseline, Month 6
Title
Change in Intravenous Iron Use
Description
Change in intravenous iron use (mg) from Baseline to Month 6.
Time Frame
Baseline, Month 6
Secondary Outcome Measure Information:
Title
Percent Change in Calcium
Description
Percent change in calcium (mg/dL) from baseline to Month 6.
Time Frame
Baseline, Month 6
Title
Percent Change in Phosphorus
Description
Percent change in phosphorus (md/dl) from baseline to Month 6.
Time Frame
Baseline, Month 6
Title
Percent Change in Parathyroid Hormone (PTH)
Description
Percent change in PTH (pg/ml) from baseline to Month 6.
Time Frame
Baseline, Month 6
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Candace Grant, MD
Organizational Affiliation
NYU Winthrop
Official's Role
Principal Investigator
Facility Information:
Facility Name
Winthrop University Hospital
City
Mineola
State/Province
New York
ZIP/Postal Code
11501
Country
United States
12. IPD Sharing Statement
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A Study of Ferric Citrate to Improve Inflammation and Lipid Levels
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