Impact of Ferric Citrate vs Ferrous Sulfate on Iron Parameters and Hemoglobin in Individuals With CKD and Iron Deficiency

Impact of Ferric Citrate vs Ferrous Sulfate on Iron Parameters and Hemoglobin in Individuals With Moderate to Severe Chronic Kidney Disease (CKD) With Iron Deficiency

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02888171

Enrollment

Registered

2016-09-02

Start date

2016-09-30

Completion date

2019-03-30

Last updated

2020-03-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Anemia, Chronic Kidney Disease, Iron Deficiency

Brief summary

The main objective of the study is to compare the impact of oral ferric citrate compared to standard of care oral ferrous sulfate on serum iron, percent transferrin saturation, ferritin, hepcidin and hemoglobin levels in individuals with moderate to severe chronic kidney disease (CKD) and absolute iron deficiency.

Detailed description

Ferric citrate is an FDA-approved oral phosphorus binder that has been shown to be effective in reducing serum phosphorus and fibroblast growth factor 23 (FGF23) concentrations and increasing iron stores and hemoglobin in individuals with non-dialysis-dependent CKD who have iron-deficiency anemia. This may prove to be advantageous in individuals with pre-dialysis CKD who require iron supplementation for iron-deficiency anemia. This is because ferric citrate may not only restore iron stores in individuals who are iron deficient, but by lowering FGF23 concentrations, ferric citrate may increase local and systemic concentrations of 1,25-dihydroxyvitamin D, a powerful inhibitor of hepcidin synthesis, potentially attenuating the increase in hepcidin following oral iron supplementation. When compared to standard iron supplementation therapies (e.g., oral ferrous sulfate) that powerfully stimulate hepcidin secretion, this may then allow for greater iron bioavailability by increasing iron absorption in the gut while also reducing the degree of iron sequestration in reticuloendothelial system stores. However, little is known about the comparative effectiveness of treatment with oral ferric citrate vs. oral ferrous sulfate (currently the standard of care) in increasing iron stores and hemoglobin in iron-deficient CKD patients. If ferric citrate is shown to not only improve overall iron status, but also partially mitigate the long-term effects of iron supplementation on hepcidin secretion by increasing endogenously produced 1,25-dihydroxyvitamin D, this may indicate that ferric citrate can provide superior short- and long-term effects on iron-restricted erythropoiesis in CKD as compared to the current standard of care. The main objectives of the study are to compare the impact of ferric citrate compared to standard of care ferrous sulfate on serum iron, percent transferrin saturation (TSAT), ferritin, hemoglobin and hepcidin concentrations in individuals with moderate to severe CKD and absolute iron deficiency.

Interventions

DRUGferric citrate

Participants randomized to the ferric citrate arm will take 2 grams of ferric citrate three times a day with meals.

DRUGferrous sulfate

Participants randomized to the ferrous sulfate arm will take 325 mg of ferrous sulfate three times a day.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Age 18 years or greater * Moderate to severe CKD not requiring dialysis (eGFR 15 - 45 ml/min/1.73 m2 by CKD-EPI) * Absolute iron deficiency (serum ferritin \<300ng/ml and Transferrin Saturation \< 30%)

Exclusion criteria

* Hemoglobin concentrations \> 13 g/dL * Known disorder of iron homeostasis (e.g., hemochromatosis) * Known gastrointestinal disorder (irritable bowel disease, inflammatory bowel disease) * Known liver disease (ALT/AST or bilirubin \> 3x normal) * Serum phosphorus concentrations \< 3.0 mg/dL * Any known cause of anemia other than iron deficiency or CKD (e.g., sickle cell anemia) * Symptomatic gastrointestinal bleeding within 12 weeks prior to the screening visit. * Subjects receiving any form of renal replacement therapy including hemodialysis, peritoneal dialysis, or renal transplant. * Pregnancy or lactation in female participants * Severe anemia defined as a hemoglobin \< 8.0 g/dL for males or a hemoglobin \<7.0 g/dL for females. * Receipt of erythropoiesis stimulating agents within 4 weeks of screening. * Receipt of intravenous iron therapy within 8 weeks of screening. * Blood transfusion within 4 weeks of screening * Known allergies or severe adverse reactions to previous oral iron therapy * Current use of oral phosphorus binders. * Current use of an active vitamin D analog

Design outcomes

Primary

Measure	Time frame	Description
Change in Ferritin From Baseline to End of Treatment	Baseline and 12 weeks	The change in serum ferritin concentrations from the baseline of the study to the 12 week time point.
Change in Transferrin Saturation From Baseline to End of Treatment	Baseline and 12 weeks	The change in serum transferrin saturation from the baseline to the end of treatment

Secondary

Measure	Time frame	Description
Change in Hemoglobin From Baseline to End of Treatment	Baseline and 12 weeks	The change in hemoglobin concentrations from the baseline visit to the 12-week time point.
Change in Hepcidin From Baseline to the End of Treatment	Baseline and 12 weeks	The change in hepcidin concentrations from the baseline visit to the 12-week time point.
Change in Fibroblast Growth Factor 23 From Baseline to the End of Treatment	Baseline and 12 weeks	The change in fibroblast growth factor 23 concentrations from the baseline visit to the 12-week time point.

Countries

United States

Participant flow

Recruitment details

Participants were recruited from the nephrology outpatient clinics at the University of Alabama at Birmingham (UAB) from September 2016 to October 2018.

Pre-assignment details

Participants who were taking oral iron supplements at the time of the screening visit were allowed to participate but had to undergo a wash-out period of at least 4 weeks prior to randomization.

Participants by arm

Arm	Count
Ferric Citrate Participants randomized to the ferric citrate arm will receive 2 grams of ferric citrate three times a day with each meal. ferric citrate: Participants randomized to the ferric citrate arm will take 2 grams of ferric citrate three times a day with meals.	30
Ferrous Sulfate Participants randomized to the ferrous sulfate arm will receive 325 mg of ferrous sulfate three times a day ferrous sulfate: Participants randomized to the ferrous sulfate arm will take 325 mg of ferrous sulfate three times a day.	30
Total	60

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	0	1
Overall Study	Lost to Follow-up	2	1
Overall Study	Withdrawal by Subject	3	2

Baseline characteristics

Characteristic	Ferric Citrate	Total	Ferrous Sulfate
Age, Continuous	60 years STANDARD_DEVIATION 12	62 years STANDARD_DEVIATION 11	63 years STANDARD_DEVIATION 11
body mass index	37 kg/m^2 STANDARD_DEVIATION 8	36 kg/m^2 STANDARD_DEVIATION 8	36 kg/m^2 STANDARD_DEVIATION 9
calcium	9.3 mg/dL STANDARD_DEVIATION 0.4	9.3 mg/dL STANDARD_DEVIATION 0.6	9.3 mg/dL STANDARD_DEVIATION 0.7
diastolic blood pressure	74 mmHg STANDARD_DEVIATION 11	73 mmHg STANDARD_DEVIATION 10	73 mmHg STANDARD_DEVIATION 10
estimated glomerular filtration rate	33 ml/min/1.73m^2 STANDARD_DEVIATION 12	31 ml/min/1.73m^2 STANDARD_DEVIATION 13	26 ml/min/1.73m^2 STANDARD_DEVIATION 14
ferritin	90 ng/ml STANDARD_DEVIATION 70	95 ng/ml STANDARD_DEVIATION 65	100 ng/ml STANDARD_DEVIATION 59
hemoglobin	11.4 g/dL STANDARD_DEVIATION 1	11.2 g/dL STANDARD_DEVIATION 1	11.0 g/dL STANDARD_DEVIATION 1
phosphorus	3.7 mg/dL STANDARD_DEVIATION 0.5	3.8 mg/dL STANDARD_DEVIATION 0.7	3.9 mg/dL STANDARD_DEVIATION 0.8
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	16 Participants	33 Participants	17 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	14 Participants	27 Participants	13 Participants
Region of Enrollment United States	30 participants	60 participants	30 participants
Sex: Female, Male Female	20 Participants	39 Participants	19 Participants
Sex: Female, Male Male	10 Participants	21 Participants	11 Participants
systolic blood pressure	136 mmHg STANDARD_DEVIATION 21	135 mmHg STANDARD_DEVIATION 20	134 mmHg STANDARD_DEVIATION 20
transferrin saturation	18 % STANDARD_DEVIATION 6	18 % STANDARD_DEVIATION 6	19 % STANDARD_DEVIATION 6

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 30	0 / 30
other Total, other adverse events	26 / 30	24 / 30
serious Total, serious adverse events	0 / 30	0 / 30

Outcome results

Primary

Change in Ferritin From Baseline to End of Treatment

The change in serum ferritin concentrations from the baseline of the study to the 12 week time point.