Clinical trial NCT02661295: 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
Overall status: TERMINATED
Phase: PHASE4
Conditions: End Stage Renal Disease
Hyperphosphatemia
Chronic Inflammation
Lead sponsor: Winthrop University Hospital
Sponsor class: OTHER
Collaborators: name: Keryx Biopharmaceuticals
First posted: 2016-01-22
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: OTHER

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:

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.

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

Primary outcomes:
measure: Percent Change in Total Cholesterol
timeFrame: Baseline, Month 6
measure: Percent Change in LDL-Cholesterol
timeFrame: Baseline, Month 6
measure: Percent Change in HDL Cholesterol
timeFrame: Baseline, Month 6
measure: Percent Change in Triglycerides
timeFrame: Baseline, Month 6
measure: Percent Change in TNF-alpha
timeFrame: Baseline, Month 6
measure: Percent Change in IL-6
timeFrame: Baseline, Month 6
measure: Percent Change in IL-8
timeFrame: Baseline, Month 6
measure: Percent Change in Ferritin
timeFrame: Baseline, Month 6
measure: Percent Change in C-reactive Protein
timeFrame: Baseline, Month 6
measure: Percent Change in Homocysteine
timeFrame: Baseline, Month 6
measure: Change in Intravenous Iron Use
timeFrame: Baseline, Month 6
Secondary outcomes:
measure: Percent Change in Calcium
timeFrame: Baseline, Month 6
measure: Percent Change in Phosphorus
timeFrame: Baseline, Month 6
measure: Percent Change in Parathyroid Hormone (PTH)
timeFrame: Baseline, Month 6
Other outcomes:
Locations:
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
Study officials:
affiliation: NYU Winthrop
name: Candace Grant, MD
role: PRINCIPAL_INVESTIGATOR
References: