Clinical trial NCT02661295
Conditions: End Stage Renal Disease Hyperphosphatemia Chronic Inflammation
Sponsor: Winthrop University Hospital
Start date: 2015-07-01; Completion date: 2018-03-15
Enrollment: 38 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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.

Arms: arm 1: Ferric citrate at a starting dose of 2 tablets with each meal will be given to all participants.
Interventions: intervention 1: Ferric Citrate
Intervention descriptions: intervention 1: 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.

Protocol documents:
Prot_SAP_000.pdf: 
 
Official Title: 
The Effect of Ferric Citrate on Inflammation and Lipid Levels in Patients 
on Hemodialysis   
NCT Number: 
NCT02661295 
Study Number: 
WUH 756275-1 
Document Type:  
Study Protocol and Statistical Analysis Plan 
Date of the 
Document: 
• 
April 28, 2017 
 
 


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Short Title: A STUDY OF FERRIC CITRATE TO IMPROVE INFLAMMATION  
AND LIPID LEVELS 
 
 
Full Title: THE EFFECT OF FERRIC CITRATE ON INFLAMMATION AND 
LIPID LEVELS IN PATIENTS ON HEMODIALYSIS 
 
 
 
 
 
Institution: 
 
           Winthrop University Hospital 
                                               Division of Nephrology and Hypertension 
 
 
Principal Investigator: 
Shayan Shirazian MD 
 
Sub-Investigators:  
Paula Dutka RN 
 
Kathleen Rice RN 
 
 
 
Site Director/Coordinator:  Candace Grant MD 
 
Funding:                                Keryx Biopharmaceuticals, Investigator Initiated Research 
Program  
 
Site:  
The Winthrop Dialysis Center, Mineola, NY 
 
Winthrop Dialysis at Bethpage, Bethpage, NY 
 
 
 
 
 
 
 
 
 
 
 
 
 


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SUMMARY 
 
Short Title:                            A STUDY OF FERRIC CITRATE TO IMPROVE  
                                                INFLAMMATION AND LIPID LEVELS 
Summary of Rationale:  
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 we 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.  
 
Therapeutic Agent:  
Ferric citrate is a salt that contains approximately 210 mg 
of ferric iron. Ferric citrate has been used as a phosphate 
binder in patients with pre-dialysis chronic kidney disease 
and in patients with end stage renal disease on 
hemodialysis. This medication is currently approved as a 
phosphate binder for patients on hemodialysis and 
peritoneal dialysis.   
 
Objective:  
To determine the effect of ferric citrate on inflammatory 
markers and lipid levels in patients with end stage renal 
disease on hemodialysis.  
 
Hypothesis :                           Oral ferric citrate will decrease levels of inflammatory 
markers and lipid levels. 
 
 


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Study Design: 
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. 
 
 
Sample Size: 
45 enrolled with a target of 30 patients that complete the 
treatment 
 
 
Eligibility Criteria:  
Patients on hemodialysis at least 6 months and receiving a 
phosphate binder with serum phosphorus levels between 
2.5 and 8.0, normal serum calcium levels, and on 
maintenance iron therapy are potentially eligible 
 
Intervention and Dosage:     Study participants will receive ferric citrate at a starting 
dose of 2 tablets with each meal if serum phosphorus levels 
are ≥ 5.5 mg/dL calcium levels are in the normal range and 
ferritin  ≥ 200 and < 600 ng/ml after a minimum 2 week 
wash out period. 
 
Study Duration: 
12 Months 
 
 
 
Procedures: 
At screening a medical history will be completed and a 
screening data set recorded for patients that meet study 
eligibility. A unique ID number will be assigned and 
participants will enter a minimum 2-week washout period 
from other phosphorus binders. 
 
 
At Day 0, for study participants with serum phosphorus 
levels ≥ 5.5 mg/dl, calcium within the normal range and 
ferritin  ≥ 200 and < 600 ng/ml baseline levels of 
inflammatory markers and lipid levels will be drawn. These 
participants will enter the treatment phase of the study. 
 


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For the first 2 months, calcium and phosphorus levels will 
be checked every 2 weeks and then monthly. At each visit 
Ferric citrate doses will be adjusted accordingly (see 
Appendix 1). Ferric citrate pill counts will be performed for 
each participant. 
 
 
Study outcomes will be collected at Day 0, 3 months and 6 
months 
 
 
Outcomes: 
Inflammatory Markers: Percent Change in ferritin, cRP, 
homocysteine, TNF-alpha, IL-6, IL-8 
Cholesterol Markers: Percent Change in TC, LDL, HDL 
Other: Intravenous iron use, Percent Change in Ca, Phos, 
PTH, Hemoglobin A1c levels 
 
 


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PURPOSE OF THE STUDY AND BACKGROUND 
 
1 Objective 
 
To determine the effect of oral ferric citrate on inflammatory markers and lipid 
levels.  
 
1.1 Hypothesis:  
 
Oral ferric citrate will reduce levels of inflammatory markers and lipid levels in 
patients on hemodialysis.  
 
2 Background and Rationale –  
 
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 age, sex 
and race matched controls from the general population without renal disease (1). 
This exorbitant risk has been attributed not only to traditional cardiovascular risk 
factors, but also risk factors more specific to ESRD including chronic 
inflammation and vascular calcification (2). Chronic inflammation is particularly 
prevalent in patients with ESRD (3). Increases in oxidative stress causing increased 
free radical production and low antioxidant levels are common (4). Parenteral iron 
therapy, which is common in patients on dialysis, may contribute to this increase 
in oxidative stress (5) leading to increased inflammation (6) and a higher 
cardiovascular risk (7). Vascular calcification is highly prevalent and often severe 
in patients with ESRD (8). This vascular calcification contributes to the high rates 
of cardiovascular death seen in patients with ESRD. Risk factors for calcification 
include hyperphosphatemia, high calcium intake and high calcium X phosphorus 
product (9).  
 
In a prospective cohort study of 10,044 incident hemodialysis patients, treatment 
with a phosphate binder was independently associated with improved survival (10). 
Non-calcium based binders may further decrease cardiovascular risk (11). 
Sevelamer, a non-calcium-containing phosphate binder, has been shown to have 
anti-inflammatory properties and to lower serum lipid levels and calcium 
phosphate product in patients on hemodialysis (11-14). Ferric citrate is a novel 
phosphorus binder that has been shown to improve serum phosphorus levels and 
decrease intravenous iron requirements for patients on hemodialysis (15). 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 oxidative stress and inflammation, 3) 
binding endotoxin in the gut (14), and 4) improving lipid metabolism. The purpose 
of this study is to examine the effect of ferric citrate on inflammatory markers and 
lipid levels. 
 
 


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CHARACTERISTICS OF THE RESEARCH POPULATION 
 
3 Experimental Plan 
 
3.1 Number of Patients  
 
45 hemodialysis patients  
 
3.2 Estimated Study Duration/Timeline:  
 
12 months: 3 months for participant recruitment, 2-week wash-out period, a 6 
month treatment period, and 3 months for data analysis and manuscript 
preparation.  
 
3.3 Patient Eligibility 
 
Adult patients with ESRD on three times per week hemodialysis at least 6 months 
prior to screening and receiving therapy with a phosphate binder and maintenance 
iron for at least 1 month prior to screening are potentially eligible.  
 
3.3.1 Inclusion Criteria 
 
1- Hemodialysis treatment for ≥ 6 months 
2- Phosphate binder treatment for ≥ 1 month  
3- Maintenance iron therapy with no more than 125mg IV iron weekly for ≥ 1 
month 
4- Serum phosphorus levels between 2.5 and 8.0 at screening and phosphorus ≥ 
5.5 mg/dL after the washout period 
5- Serum ferritin ≥ 200 and  < 600 ng/ml after the washout period 
6- Serum calcium levels within normal range 
7- Predicted survival greater than 6 months  
 
3.3.2 Exclusion criteria 
 
1- Age < 18 years 
2- Failure to provide informed consent 
3- Intact PTH < 70 pg/ml or > 1,000 pg/ml 
4- URR < 65% 
5- Niacin and nicotinamide use 
6- Oral iron use  
7- Vitamin C supplement use 
8- Parathyroidectomy within 6 months before the screening visit  
9- Active malignancy 
10- Patients undergoing hemodialysis via a catheter or AV graft  
11- Received any amount more than 250mg of IV iron over the two weeks prior to 
screening  


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12- Whole blood transfusion within 3 months prior to screening  
13- Active bleeding from any site other than the dialysis access within 1 month 
prior to screening  
14- Hospitalization within 1 month prior to screening  
15- Current febrile illness or active chronic infection 
16- Ongoing or uncontrolled inflammatory disorder  
17- Liver cirrhosis 
18- Likelihood of imminent renal transplantation 
 
 
3.4 Patient Enrollment 
 
All hemodialysis patients at Winthrop University Hospital Dialysis centers will be 
potentially eligible. It is estimated that approximately 300 hemodialysis patients 
are dialyzed at these centers 
 
 


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METHODS AND PROCEDURES 
 
4 Study Procedures 
 
4.1 Study Design  
 
This study will be designed as an experimental trial in which 45 hemodialysis 
patients will be given ferric-citrate after a 2-week wash period from phosphate 
binders.  
 
4.2 Screening 
 
After providing informed consent, screening procedures will be initiated. The 
baseline data set will be recorded as below. Participants will be assigned a unique 
ID number. Participants that meet all inclusion and exclusion criteria will be 
entered into the study.  
 
4.3 Wash-out  
 
Wash-out will begin immediately after screening for participants that meet study 
eligibility. All previous phosphate binders will be discontinued for a minimum of 
2 weeks. At the end of 2 weeks, calcium, phosphorus, Tsat and ferritin levels will 
be measured and all participants with phosphorus levels ≥ 5.5 mg/dL, calcium 
within the normal range and ferritin  ≥ 200 and < 600 ng/mL will have blood 
drawn for levels of inflammatory markers and lipids and will enter the treatment 
phase of the study. For participants who do not meet this criteria at the end of the 
initial two week washout period, calcium, phosphorus, Tsat and ferritin levels will 
be checked for entry criteria each week thereafter. If the participant remains 
ineligible to enter the treatment phase after 4 weeks, he/she will be withdrawn 
from the study. 
 
4.4 Treatment 
 
Ferric citrate will be initiated in 1gm capsules containing approximately 210mg of 
ferric iron at a dose of 6 capsules per day (2 with each meal). Ferric citrate will be 
titrated every 2 weeks throughout the trial by the primary investigator using serum 
calcium and phosphorus values and a previously defined titration schedule 
(Appendix 1). Patients will be on study Ferric Citrate for a 6 month study 
treatment period.  
 
4.5 Concomitant Medications 
 
Only study investigators will adjust intravenous iron therapy throughout the 
duration of the trial. Participants with a serum ferritin of < 200 ng/ml will be 
given a 1 gm load of ferric gluconate delivered over 8 hemodialysis sessions. For 
participant with a ferritin > 600 ng/ml, all intravenous iron therapy will be 


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discontinued. All other medications except prohibited medications (see below) 
will be dosed based on the discretion of the treating physicians  
 
4.6 Prohibited Therapy 
 
Any phosphate binder other than ferric citrate  
Any other investigational medication 
Niacin and nicotinamide 
Oral iron therapy 
Vitamin C supplements 
 
4.7 Treatment Failure  
 
Subjects will be considered treatment failures if they are ≥80% compliant with 12 
doses/d of ferric citrate and have two consecutive serum phosphorus values >8.0 
mg/dl (serum phosphorus will be checked at next HD session if >8.0). These 
subjects will be discontinued from the study drug and will resume their previous 
phosphate binder, but will be encouraged to complete all study visits. 
 
4.8 Study Drug With-holding  
Subjects will be stopped on study drug if: 1) they have an adverse event 
necessitating study drug discontinuation, 2) Serum phosphorus < 2.5 3) 
Investigator’s discretion  
 
4.9 Laboratory Considerations 
All study outcomes will be drawn at the onset of hemodialysis. All labs will be 
non-fasting. Attempts will be made to draw labs at approximately the same time 
of the day at time 0, 3 months and 6 months.  
 
4.10 Safety Considerations 
 
Adverse event information will be collected from the time a consented subject is 
screened until the end of the study. All adverse and serious adverse events will be 
recorded according to standard definitions.  
 
Any SAE, including death from any cause, which occurs during this trial, if 
related or possibly related to the study drug, must be reported to Keryx within 24 
hours of becoming aware of the SAE. The site will submit the SAE Worksheet to 
Keryx. Please forward the SAE (available 24 hours/day, 7 days/week) to the 
following: 
 
Phone: Keryx 1-212-531-5756 
Email:   Madlen.Malinowski@keryx.com 
Fax:      Keryx 1-646-417-5457 
 


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A report must be submitted within 24 hours of the initial reporting to Keryx.  
Withdrawal from the trial and all therapeutic measures taken will be at the 
discretion of the Principal Investigator (PI).  All SAEs (related or of possible 
relationship to the study drug) will be followed until satisfactory resolution or 
until the PI deems the event to be chronic or the subject to be stable. 
Keryx will be responsible for reporting of any SAE to the FDA if applicable.  
Keryx will notify the FDA of any related, unexpected, fatal or life-threatening 
experience (expedited report) associated with the use of the study drug. The 
investigator is responsible for informing the Institutional Review Board (IRB), 
according to the IRB’s requirements.   
 
 
5 Dataset 
 
5.1 Recorded at Screening (Time -2 weeks)  
 
5.1.1 Name 
5.1.2 Date of enrollment  
5.1.3 Age 
5.1.4 Gender 
5.1.5 Race 
5.1.6 Ethnicity  
5.1.7 Cause of ESRD  
5.1.8 Medication list including statin use and current binder use  
5.1.9 ESA, vitamin D and vitamin D analog use over the 1 month prior 
to screening 
5.1.10 Comorbid condition list including CAD/CVD status 
5.1.11 Dialysis Vintage 
5.1.12 KT/V 
5.1.13 URR 
5.1.14 Hemoglobin 
5.1.15 Serum Albumin 
5.1.16 intact-PTH  
 
5.2 Drawn at -2 days  
5.2.1 Serum Calcium, Phosphorus 
5.2.2 Serum Iron, TIBC, Ferritin 
 
5.3 Recorded prior HD # 1 (Time 0)  
5.3.1 Serum Albumin  
5.3.2 Intravenous iron use over the 6 months prior to study entry  
 
5.4 Drawn prior to HD # 1 (Time 0)  
5.4.1 Fasting serum Total Cholesterol, LDL, HDL, Triglycerides 
5.4.2 Inflammatory markers (ferritin, cRP, homocysteine, TNF-alpha,  
         IL-6, IL-8) 


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5.4.3 Hemoglobin A1c 
 
5.5 Recorded monthly 
5.5.1 Calcium and phosphorus levels (and every two week for the first 2  
         months) 
5.5.2 Ferric citrate pill counts  
 
5.6 Drawn at 3 months  
5.6.1 Serum Calcium, Phosphorus 
5.6.2 Fasting serum Total Cholesterol, LDL, HDL, Triglycerides 
5.6.3 Inflammatory markers (ferritin, cRP, homocysteine, TNF-alpha,  
         IL-6, IL-8) 
5.6.4 Serum Iron, TIBC, Ferritin 
5.6.5 Hemoglobin A1c 
 
5.7 Recorded at 3 months  
 
5.7.1 Serum Albumin  
5.7.2 Intact-PTH  
5.7.3 Intravenous iron use over the prior 3 months  
5.7.4 Ferric citrate pill count  
 
5.8 Drawn at end of study (Time 6 months)  
5.8.1 Serum Calcium, Phosphorus  
5.8.2 Serum Iron, TIBC, Ferritin 
5.8.3 Fasting serum Total Cholesterol, LDL, HDL, Triglycerides 
5.8.4 Inflammatory markers (ferritin, cRP, homocysteine, TNF-alpha,  
         IL-6, IL-8) 
5.8.5 Hemoglobin A1c 
 
 
5.9 Recorded at end of study (Time 6 months) 
5.9.1 Serum Albumin  
5.9.2 intact-PTH 
5.9.3 Intravenous iron use over the prior 3 months  
5.9.4 Ferric citrate pill count  
 
6 Removal and Replacement of Patients 
 
6.1 Removal of Patients (early termination) 
 
In accordance with the current version of the Declaration of Helsinki and other 
applicable regulations, a patient has the right to withdraw from the study at any 
time and for any reason without prejudice to his or her medical care and 
treatment. 
 


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The investigator will withdraw any patient who is unable to complete the full 6 
months of study due to hospitalization or other unexpected event.  
 
Considerations for patient withdrawal include:  
 
6.1.1 Subject request 
6.1.2 Lost to follow-up 
6.1.3 Pregnancy  
6.1.4 Kidney Transplantation  
6.1.5 Safety considerations 
 
Data for these patients will be included in the final statistical analysis. 
 
6.2 Replacement of Patients 
 
In the event of withdrawal under the circumstances stated in 6.1, then the patient 
accrual list will be decremented by one, allowing for full enrollment of 45 
patients. 
 
 
7 Statistical Considerations 
 
7.1 Outcomes 
 
7.1.1 Cholesterol Markers: Percent Change in TC, LDL, HDL,       
         Triglycerides 
7.1.2 Inflammatory Markers: Percent Change in ferritin, cRP,  
         homocysteine, TNF-alpha, IL-6, IL-8 
7.1.3 Other: Intravenous iron use, Change in Ca, Phos, PTH, Hemoglobin  
         A1c levels  
 
7.2 Covariates  
 
Name, Age, Gender, Race, Ethnicity, ESA use, IV iron use, vitamin D and 
vitamin D analog use, CAD/CVD status, Dialysis Vintage, KT/V/URR, 
Hemoglobin, Hemoglobin A1c, Serum Albumin 
 
7.3 Analysis 
All outcomes are continuous variables. Student’s t test will be used to test for 
statistical significance. Multiple regression analysis will be used for controlling 
covariates and testing the interaction among covariates.  Analysis of repeated 
outcome measures will be based on hierarchical linear model (HLM) including 
trajectories over time within each patient. 
 


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8 Confidentiality and storage of data   
8.1 All records will be kept in a locked file cabinet.  The subject’s names will be 
kept on a password protected database and will be linked only with a study 
identification number for this research. There will only be one copy of the file 
linking a subject’s name to his/her unique identifier. All data will be entered into 
a computer that is password protected and accessible only by study investigators.  
8.2 Clinical information will not be released without written permission of the 
subject, except as necessary for viewing by study investigators and monitoring by 
IRB, the FDA and the OHRP. 
8.3 Data will be stored in a locked office of the investigators and maintained for a 
minimum of three years after the completion of the study. 
 
 


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RISK/BENEFIT ASSESSMENT 
 
9    Risk 
9.1 Patients will undergo at least a 2 week washout period where their current 
phosphate     
      binder will be temporarily discontinued. During this period they may run the risk 
of elevated blood phosphorus levels but will be monitored closely and will be 
restarted on their prior phosphorus binder if two consecutive phosphorus values 
are over 8.0 mg/dL.  
9.2 The most serious possible side effect of ferric citrate is iron overload.  
9.3 The most common side effects are diarrhea, nausea, vomiting, cough and dark 
stools.  
9.4 There may be side effects and reactions which are unknown at this time and so it 
is not certain how each patient will respond to ferric citrate. Some patients may 
have an allergic reaction to the drug.  If they have a very bad allergic reaction, this 
can be a life threatening medical condition. 
 
10 Protection against risk 
The researchers will discuss possible difficulties and the chances that they will 
happen. Potential risks and discomforts will be minimized to the greatest extent 
possible by weekly monitoring of patients and adjustment of the study drug. Patients 
will be withdrawn from the study upon evidence of study related difficulty or adverse 
events. After study withdrawal or end of study, patients will receive the necessary 
follow-up as detailed in the methods and procedures section above.  If as a result of 
study participation patients experience physical injury from known or unknown risks 
of study, immediate medical care and treatment, including hospitalization, if 
necessary, will be available. No funds have been set aside for compensation; therefore 
patients will be responsible for the costs of their medical treatment, either, directly or 
through their medical insurance and/or other forms of medical coverage. 
 
11 Potential benefits to the subjects 
It is not known if the treatment received will be of benefit to the patient.  There may 
be no direct benefit from agreeing to participate in this study.  However, this study 
may help others in the future determine the effect of ferric citrate on inflammatory 
markers and lipid levels in patients with end stage renal disease on hemodialysis. 
 
 


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INVESTIGATOR’S QUALIFICATIONS AND EXPERIENCE 
 
All investigators have completed the CITI tutorial and have received training in the 
protection of human subjects. A copy of a valid CITI certificate and recent CV/resume of 
each investigator will be submitted to the IRB  
 
 


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SUBJECT IDENTIFICATION, RECRUITMENT AND CONSENT/ASSENT 
 
12  Method of Subject Identification and Recruitment 
Patients will be recruited from a WUH private and secure nephrology patient 
database.  
 
13  Process of Consent 
Consent will be obtained by the principal investigator and sub-investigators listed on 
the protocol and consent form. Each page of the consent will be reviewed with the 
patient. Patients will be given an opportunity to ask questions after each page. 
Patients will be asked to repeat pertinent parts of the consent to ensure 
comprehension. The patient will be offered and given an opportunity to take the 
consent home for further review as needed. The PI will be responsible for ensuring 
that valid consent is obtained and documented for all subjects. 
 
14  Cost to the Subject 
The study medication (Ferric Citrate) will be supplied by Keryx Biopharmaceuticals 
at no cost to the patient. All study costs including any tests, examinations, or other 
procedures associated with this study that are not a part of the patients routine 
medical care will be paid for by Keryx Biopharmaceuticals. The rest of the medical 
care that the patient will receive in this study will be considered standard care and 
thus would be recommended regardless of the patient’s decision to participate in this 
study. These costs will be billed to the patient or the patient’s insurance carrier. The 
patient will be responsible for any co-payments and/or deductibles as required by 
your insurance that are associated with routine medical care.   
 
15  Payment for Participation 
The patient will not be paid for participation but will receive a one-time $50.00 
compensation for their expenses and time spent directly related to this study. To 
protect the subject’s right to withdraw without penalty, the patient does not have to 
complete the entire study to be eligible to receive payment. 
  
 
 


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REFERENCES 
 
1. 
Levey AS, Beto JA, Coronado BE, Eknoyan G, Foley RN, Kasiske BL, Klag MJ, 
Mailloux LU, Manske CL, Meyer KB, Parfrey PS, Pfeffer MA, Wenger NK, Wilson PW, 
Wright JT, Jr. Controlling the epidemic of cardiovascular disease in chronic renal 
disease: what do we know? What do we need to learn? Where do we go from here? 
National Kidney Foundation Task Force on Cardiovascular Disease. American journal of 
kidney diseases : the official journal of the National Kidney Foundation1998 
Nov;32(5):853-906. 
2. 
Wang AY, Lam CW, Chan IH, Wang M, Lui SF, Sanderson JE. Sudden cardiac 
death in end-stage renal disease patients: a 5-year prospective analysis. 
Hypertension2010 Aug;56(2):210-6. 
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13. 
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(Refer to Appendix 1). 
 
 


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Appendix 1. Ferric Citrate titration schedule 
Adapted from Appendix 1:  J Am Soc Nephrol. 2015 Feb;26(2):493-503 
Ferric Citrate Starting Dose (6 tablets per day) 
Check phosphorus 
P = 2.5 to 3.4 mg/dL 
P = 3.5 to 5.5 mg/dL 
P = 5.6 to 6.9 mg/dL 
P > 6.9 mg/dL 
Increase dose by 3 
tablets per day for 
a daily maximum 
of 12 tablets per 
day). 
P < 2.5 mg/dL 
Hold ferric citrate 
until serum P ≥ 6.5 
md/dL then restart 
at a lower dose 
after consultation 
with the CCC. 
Reduce dose by one 
tablet per day. 
No action required. 
Phosphorus is at 
goal. 
Increase dose by 
one tablet per day.