Chronic Kidney DiseaseNCT02888171
Impact of Ferric Citrate vs Ferrous Sulfate on Iron Parameters and Hemoglobin in Individuals With CKD and Iron Deficiency
A study testing ferric citrate and ferrous sulfate in people with Chronic Kidney Disease and Iron Deficiency, run by University of Alabama at Birmingham at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Kidney Disease, Iron Deficiency, Anemia
- What is being tested?
- ferric citrate and ferrous sulfate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2016to 30 Mar 2019
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%)
Who cannot join
- 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)
Show all 16Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama at Birmingham
Birmingham, Alabama, 35294
About this study
Official title: 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
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.
Read the 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.
- Conditions
- Chronic Kidney Disease, Iron Deficiency, Anemia
- Being tested
- ferric citrate, ferrous sulfate
- Medical subject headings
- Renal Insufficiency, Chronic, Iron Deficiencies, Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ferric citrateDrug
Also called Auryxia
Participants randomized to the ferric citrate arm will take 2 grams of ferric citrate three times a day with meals.
ferrous sulfateDrug
Participants randomized to the ferrous sulfate arm will take 325 mg of ferrous sulfate three times a day.
| Study group | Role | What they receive |
|---|---|---|
| ferric citrate | Experimental | Participants randomized to the ferric citrate arm will receive 2 grams of ferric citrate three times a day with each meal. Receives: Drug: ferric citrate |
| ferrous sulfate | Active comparator | Participants randomized to the ferrous sulfate arm will receive 325 mg of ferrous sulfate three times a day Receives: Drug: ferrous sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and 12 weeks
Change in Transferrin Saturation From Baseline to End of Treatment
The change in serum transferrin saturation from the baseline to the end of treatment
Measured: Baseline and 12 weeks
Secondary outcomes (3)
Change in Hemoglobin From Baseline to End of Treatment
The change in hemoglobin concentrations from the baseline visit to the 12-week time point.
Measured: Baseline and 12 weeks
Change in Hepcidin From Baseline to the End of Treatment
The change in hepcidin concentrations from the baseline visit to the 12-week time point.
Measured: Baseline and 12 weeks
Change in Fibroblast Growth Factor 23 From Baseline to the End of Treatment
The change in fibroblast growth factor 23 concentrations from the baseline visit to the 12-week time point.
Measured: Baseline and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2016 (estimated)
- Study startSep 2016
- Primary completion12 Feb 2019
- Study completion30 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Kidney DiseaseStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Orlando M. Gutierrez, MD, MMSc, University of Alabama at Birmingham
- Investigators
- Orlando M Gutierrez, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02888171
- Sponsor's protocol ID
- F160318006
- Status last verified
- Mar 2020
- First submitted
- 30 Aug 2016
- Last updated
- 24 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Womack R, Berru F, Panwar B, Gutierrez OM. Effect of Ferric Citrate versus Ferrous Sulfate on Iron and Phosphate Parameters in Patients with Iron Deficiency and CKD: A Randomized Trial. Clin J Am Soc Nephrol. 2020 Sep 7;15(9):1251-1258. doi: 10.2215/CJN.15291219. Epub 2020 Jul 21.
PubMed 32694162
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02888171
- Acronym / sponsor ID
- F160318006
- Conditions
- Chronic Kidney Disease, Iron Deficiency, Anemia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Study start
- Sep 2016 (actual)
- Primary completion
- 12 Feb 2019 (actual)
- Study completion
- 30 Mar 2019 (actual)
- First posted
- 2 Sep 2016 (estimated)
- Results
- Posted 24 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ferric citrate | Experimental | Drug: ferric citrateParticipants randomized to the ferric citrate arm will receive 2 grams of ferric citrate three times a day with each meal. |
| ferrous sulfate | Active comparator | Drug: ferrous sulfateParticipants randomized to the ferrous sulfate arm will receive 325 mg of ferrous sulfate three times a day |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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%)
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ferric citrateAlso: AuryxiaParticipants randomized to the ferric citrate arm will take 2 grams of ferric citrate three times a day with meals. | Drug | ferric citrate |
| ferrous sulfateParticipants randomized to the ferrous sulfate arm will take 325 mg of ferrous sulfate three times a day. | Drug | ferrous sulfate |
Primary outcome
Change in Ferritin From Baseline to End of Treatment
Time frame: 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
Time frame: Baseline and 12 weeks
The change in serum transferrin saturation from the baseline to the end of treatment
3 secondary outcomes
Change in Hemoglobin From Baseline to End of Treatment
Time frame: Baseline and 12 weeks
Change in Hepcidin From Baseline to the End of Treatment
Time frame: Baseline and 12 weeks
Change in Fibroblast Growth Factor 23 From Baseline to the End of Treatment
Time frame: Baseline and 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32694162Womack R, Berru F, Panwar B, Gutierrez OM. Effect of Ferric Citrate versus Ferrous Sulfate on Iron and Phosphate Parameters in Patients with Iron Deficiency and CKD: A Randomized Trial. Clin J Am Soc Nephrol. 2020 Sep 7;15(9):1251-1258. doi: 10.2215/CJN.15291219. Epub 2020 Jul 21.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Orlando M Gutierrez, MD principal investigator
University of Alabama at Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ferric citrate and ferrous sulfate in people with Chronic Kidney Disease and Iron Deficiency, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Ferritin From Baseline to End of Treatment (time frame: Baseline and 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02888171, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2020.