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Trial record 2 of 17 for:    zerenex

Ferric Citrate in ESRD Pilot Project

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ClinicalTrials.gov Identifier: NCT03055598
Recruitment Status : Recruiting
First Posted : February 16, 2017
Last Update Posted : March 7, 2018
Sponsor:
Collaborator:
Keryx Biopharmaceuticals
Information provided by (Responsible Party):
Sreedhar Mandayam, Baylor College of Medicine

Brief Summary:

This research study is for participants that have End Stage Renal Disease (ESRD). ESRD is the last stage of chronic kidney disease. Anemia is very common in ESRD patients and require erythropoiesis-stimulating agents (ESAs) for treatment. Anemia happens when there are not enough red blood cells in your body. ESAs work by helping the bone marrow to produce red blood cells. There are two ESAs licensed for the treatment of anemia of CKD in the Unites States: epoetin alfa and darbopoetin alfa. ESA therapy is considered safe. However, major adverse effects should be acknowledged, including an increased risk of death, thromboembolic complications, stroke, heart attack, aplastic anemia, tumor progression, and others. To minimize risks of these adverse events, careful monitoring of hemoglobin levels, along with adjustment of ESA dosing, to maintain the lowest hemoglobin level clinically needed is recommended.

Ferric Citrate, also called Auryxia, is an iron-based phosphate binder that may decrease ESA usage while maintaining hemoglobin levels. Phosphate binders are medications used to reduce the body's absorption of phosphate. In a prior study, it was seen that some laboratory values, such as iron levels, changed positively in response to Auryxia. In this study we want to see if using Auryxia will cause a change in laboratory values and lower the use of ESAs in ESRD patients.


Condition or disease Intervention/treatment Phase
End Stage Renal Disease Chronic Kidney Diseases Drug: Ferric Citrate Phase 4

Detailed Description:

Iron deficiency anemia is very prevalent in end stage renal disease (ESRD) patients. Patients with ESRD require phosphate binders for hyperphosphatemia and erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron for anemia. In patients with ESRD, iron deficiency occurs more frequently, because of increased external losses of iron, decreased availability of the body's storage of iron, and perhaps a deficit in intestinal iron absorption.

ESRD patients tend to lose about 3 grams of iron every year from chronic bleeding, frequent phlebotomy and blood trapping in the dialysis apparatus. Total body iron stores of about 20-25 mg are mostly maintained by recycling from senescent red blood cell (RBC) count by macrophages of the reticulo-endothelial system. In addition, to true iron deficiency, many ESRD patients have functional iron deficiency, characterized by impaired iron release from body stores that is unable to meet the demand for erythropoiesis (also called reticuloendothelial cell iron blockade). These patients have low serum transferrin saturation (TSAT, a measure of circulating iron) and normal or high serum ferritin (a marker of body iron stores). Dietary iron absorption under usual circumstances accounts for only 1-2 mg/day and is almost equal to daily iron losses from intestinal and skin cell shedding.

For treatment of anemia caused by chronic renal disease, the United States Food and Drug Administration (FDA) has approved the use of ESA therapy. There are two ESAs licensed for the treatment of anemia of CKD in the Unites States: epoetin alfa and darbopoetin alfa. Both are glycoproteins that are manufactured using recombinant DNA technology. They stimulate erythropoiesis through the same mechanism of action as endogenous erythropoietin. The starting dose of epoetin is 50 units/kg (3000-4000 units/dose) once or twice a week, and darbepoetin is started at 0.45 mcg/kg and can be administered every 2-4 weeks. To avoid impaired erythropoiesis caused by true iron deficiency or functional iron deficiency, iron stores should be fully replenished before and during ESA therapy. ESA therapy is considered safe. However, major adverse effects should be acknowledged, including an increased risk of death, thromboembolic complications, stroke, heart attack, aplastic anemia, tumor progression, and others. To minimize risks of these adverse events, careful monitoring of hemoglobin levels, along with adjustment of ESA dosing, to maintain the lowest hemoglobin level clinically needed is recommended.

Given that ESRD is a pro-inflammatory condition, substantial elevation in serum ferritin is very common in ESRD patients. The role of iron replacement therapy in ESRD patients with high serum ferritin but low transferrin saturation is not clear at all. In fact, most anemia management protocols recommend stopping iron replacement when ferritin levels are greater than 1,200 ng/ml, even if the TSAT is below 20%. The United States Renal Data System (USRDS) reports for that 55% of prevalent ESRD patients (2012-2014) have a ferritin >800 ng/ml and 22% had ferritin>1200 ng/ml. In one of our local dialysis centers, close to 45% of patients seem to have a ferritin greater than 1,200 ng/ml and about 20% have a combination of low TSAT and high ferritin.

Ferric citrate (Auryxia) is a novel, iron-based phosphate binder that increases iron stores and decreases IV iron and ESA usage while maintaining hemoglobin levels, and may decrease the cost of ESRD care. By binding phosphate in the GI tract and decreasing absorption, ferric citrate lowers the phosphate concentration in the serum. In addition to effects on serum phosphorus levels, Auryxia has been shown to increase serum iron parameters, including ferritin, iron and TSAT. In dialysis patients treated with Auryxia in a 52-week study in which IV iron could also be administered, mean (SD) ferritin levels rose from 593 (293) ng/mL to 895 (482) ng/mL, mean (SD) TSAT levels rose from 31% (11) to 39% (17) and mean (SD) iron levels rose from 73 (29) mcg/dL to 88 (42) mcg/dL. In contrast, in patients treated with active control, these parameters remained relatively constant.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Effect of Auryxia on ESA Utilization in ESRD Patients With High Ferritin & Low Transferrin Saturation: A Pilot Project
Actual Study Start Date : May 11, 2017
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : February 2020

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Ferric Citrate
Ferric Citrate (Auryxia) will be dosed initially at 2 tablets three times a day (with meals).
Drug: Ferric Citrate
Doses can be adjusted as needed by 1 to 2 tablets up to a maximum of 12 tablets daily. Dose can be titrated at 1-week or longer intervals.
Other Name: Auryxia



Primary Outcome Measures :
  1. change in average weekly ESA dose determination from baseline to day 90 [ Time Frame: day 90 ]
    determine change in average dose of ESA use when using Auryxia

  2. change in mean serum iron from baseline to day 90 [ Time Frame: day 90 ]
    assess change in mean serum iron while using Auryxia

  3. change in mean ferritin from baseline to day 90 [ Time Frame: day 90 ]
    assess change in mean ferritin while using Auryxia


Secondary Outcome Measures :
  1. change in average weekly ESA dose determination [ Time Frame: baseline, day 30, day 60 ]
    determine change in average dose of ESA use when using Auryxia

  2. change in mean serum iron [ Time Frame: baseline, day 30, day 60 ]
    assess change in mean serum iron while using Auryxia

  3. change in mean ferritin [ Time Frame: baseline, day 30, day 60 ]
    assess change in mean ferritin while using Auryxia

  4. TSAT value [ Time Frame: baseline, day 30, day 60, day 90 ]
    values if less than 30% to greater than 30% to determine effectiveness

  5. hemoglobin value [ Time Frame: baseline, day 30, day 60, day 90 ]
    elevated serum ferritin (>1000 ng/ml) to determine effectiveness

  6. KDQOL-36 energy score [ Time Frame: Baseline and 90 days ]
    KDQOL-36 energy score to determine overall quality of life

  7. KDQOL-36 fatigue score [ Time Frame: Baseline and 90 days ]
    KDQOL-36 fatigue score to determine overall quality of life

  8. KDQOL-36 depression score [ Time Frame: Baseline and 90 days ]
    KDQOL-36 depression score to determine overall quality of life

  9. Number of participants alive or dead (Survival status) at 90 days [ Time Frame: at 90 days ]
    Measured by death (yes/no) and date



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed informed consent prior to any study specific procedures
  2. Male and females aged 18 years and older
  3. In the Investigator's opinion, expected to survive at least 3 months
  4. Able to tolerate phosphate binders
  5. ESRD and on dialysis for over 90 days
  6. Deemed stable by Investigator
  7. Serum Ferritin >1000 ng/ml (measured as average of at least 2 values in the last 3 months +/- 10 days)
  8. TSAT < 30% ( measured as average of at least 2 values in the last 30 days, +/- 10 days)
  9. Hemoglobin < 12g/dl (measured as average of at least 2 values in the last 30 days, +/- 10 days)
  10. Currently on ESA for at least 1 month, as per dialysis unit protocol

Exclusion Criteria:

  1. Inability or refusal to give informed consent
  2. Subject unwilling to take study medication for 3 months
  3. Currently on IV Iron
  4. Currently on Auryxia as phosphate binder (or received in prior 3 months)
  5. Deemed non-compliant by care team for dialysis or medication
  6. Active gastrointestinal bleed
  7. Inflammatory bowel disease
  8. History of malignancy within 5 years before screening (exceptions: squamous and basal cell carcinomas of the skin and carcinoma of the cervix in situ, or a malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence).
  9. Known allergy to oral iron products
  10. Pregnant
  11. Breastfeeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03055598


Contacts
Contact: Monica Rodriguez 713-798-6027 Monica.Rodriguez@bcm.edu
Contact: Miguel Aguirre 713-798-3529 Miguel.Aguirre@bcm.edu

Locations
United States, Texas
US Renal Care- Scott Street Recruiting
Houston, Texas, United States, 77021
Contact: Monica Rodriguez    713-798-6027    Monica.Rodriguez@bcm.edu   
Contact: Sreedhar Mandayam    713-798-8350    mandayam@bcm.edu   
Sub-Investigator: Jose Perez, MD         
Sub-Investigator: Jingyin Yan, MD         
Sub-Investigator: Charles Minard, PhD         
Principal Investigator: Sreedhar Mandayam, MD         
Sponsors and Collaborators
Sreedhar Mandayam
Keryx Biopharmaceuticals
Investigators
Principal Investigator: Sreedhar Mandayam, MD Baylor College of Medicine

Responsible Party: Sreedhar Mandayam, MD, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT03055598     History of Changes
Other Study ID Numbers: H-39364 Ferric Citrate in ESRD
First Posted: February 16, 2017    Key Record Dates
Last Update Posted: March 7, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Kidney Diseases
Renal Insufficiency, Chronic
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency
Citric Acid
Ferric Compounds
Anticoagulants
Calcium Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Hematinics