Oral Iron for Chronic Kidney Disease

(FeTCh-CKD Trial)

Recruiting at1 trial location

Overseen by Oleh Akchurin, M.D.

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Weill Medical College of Cornell University

Must not be taking: Iron therapy, Erythropoietin

Disqualifiers: Hemodialysis, Pregnancy, Rapid kidney decline, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests iron pills in children with kidney disease and mild anemia. It aims to see if taking iron improves their muscle strength, activity levels, and eating habits. The study compares children taking iron pills to those who do not over a few months.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have had iron therapy or certain blood treatments in the last 3-4 months before joining.

What data supports the effectiveness of the drug Ferrous Sulfate for chronic kidney disease?

The research indicates that oral iron, like Ferrous Sulfate, is commonly used to treat iron deficiency anemia in chronic kidney disease patients. Although the study did not find a significant difference in kidney function decline between oral and intravenous iron, oral iron was associated with fewer serious adverse events compared to intravenous iron. ^{1 2 3 4 5}

Is oral iron, like ferrous sulfate, safe for people with chronic kidney disease?

Oral iron treatments, such as ferrous sulfate, are generally considered safe for people with chronic kidney disease, but they can cause gastrointestinal issues like diarrhea and constipation. Serious adverse events were more common with intravenous iron treatments compared to oral ones. ^{1 6 7 8 9}

How does the drug Ferrous Sulfate differ from other treatments for chronic kidney disease?

Ferrous Sulfate is an oral iron supplement used to treat iron deficiency anemia in chronic kidney disease, offering a non-invasive alternative to intravenous iron, which has been associated with a higher risk of serious adverse events like cardiovascular issues and infections. ^{1 4 10 11 12}

Research Team

Oleh Akchurin, M.D.

Principal Investigator

Weill Cornell College of Medicine

Eligibility Criteria

This trial is for children aged 1-21 with chronic kidney disease and mild anemia, not on hemodialysis or expecting a transplant soon. They must have specific levels of kidney function, hemoglobin, transferrin saturation, and serum ferritin to join.

Inclusion Criteria

I am between 1 and 21 years old.

Your kidney function, measured by a formula using your height and blood test results, is too low.

Your hemoglobin level was 9.0 or higher at your last doctor's visit.

Exclusion Criteria

My kidney function is quickly getting worse, and I might need dialysis or a transplant soon.

Your blood ferritin level is less than 10 ng/mL.

You are pregnant or breastfeeding.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized into a standard of care (iron sulfate) arm vs. no iron therapy arm for 3 months

12 weeks

Routine clinic visits for blood tests

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Ferrous Sulfate (Iron Supplement)

Trial Overview The study tests if taking oral iron (ferrous sulfate) helps improve muscle strength, physical activity, and eating behavior in these kids compared to those who don't get iron therapy over a period of three months.

Participant Groups

Group I: Oral Iron therapy Experimental Treatment 1 Intervention

Participant will receive oral iron therapy.

Group II: No oral iron therapy Active Control 1 Intervention

Participant will not receive oral iron therapy for 3 months.

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Dr. Robert Min

Weill Medical College of Cornell University

Chief Executive Officer since 2024

MD, MBA

Dr. Adam R. Stracher

Weill Medical College of Cornell University

Chief Medical Officer since 2024

MD

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

Joseph W. St. Geme III

Children's Hospital of Philadelphia

Chief Medical Officer since 2021

MD, PhD, MPH

Madeline Bell

Children's Hospital of Philadelphia

Chief Executive Officer since 2015

BSc in Nursing from Villanova University, MSc in Organizational Dynamics from the University of Pennsylvania

Findings from Research

In a study involving 136 patients with stage 3 and 4 chronic kidney disease (CKD) and iron deficiency anemia (IDA), both oral ferrous sulfate and intravenous iron sucrose showed similar declines in kidney function over two years, indicating no significant difference in their effects on glomerular filtration rate (mGFR).

However, intravenous iron therapy was associated with a higher risk of serious adverse events, including cardiovascular issues and infections, compared to oral iron, suggesting that while both treatments are effective for IDA, intravenous iron may pose additional safety risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized trial of intravenous and oral iron in chronic kidney disease. Agarwal, R., Kusek, JW., Pappas, MK.[2022]

In a 1-year study involving 308 patients with iron-deficient anemia and nondialysis-dependent chronic kidney disease, only 21.6% showed a significant increase in hemoglobin after 4 weeks of oral iron therapy.

Among those who did not respond initially, less than 30% showed improvement by week 52, suggesting that alternative anemia treatments should be considered earlier for better management of anemia in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erythropoietic response to oral iron in patients with nondialysis-dependent chronic kidney disease in the FIND-CKD trial . Macdougall, IC., Bock, AH., Carrera, F., et al.[2018]

In a study of 12 weeks involving 12,969 adult patients starting hemodialysis, maintenance intravenous (IV) iron administration did not significantly improve the likelihood of achieving hemoglobin levels between 10-12 g/dL.

However, patients receiving maintenance IV iron had a 33% higher chance of reducing their erythropoietin stimulating agent (ESA) dose by more than 25% and a 27% lower risk of mortality compared to those receiving non-maintenance iron.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous iron administration strategies and anemia management in hemodialysis patients. Michels, WM., Jaar, BG., Ephraim, PL., et al.[2018]

In a study of 182 anemic patients with chronic kidney disease (CKD), oral iron supplementation prevented a decrease in hemoglobin levels over 12 months, while the control group experienced significant declines.

Oral iron was particularly effective in patients with lower kidney function (eGFR < 30 ml/min/1.73 m2) and did not negatively affect kidney function, with similar rates of adverse events in both the iron and control groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of oral iron supplementation on the progression of anemia and renal dysfunction in patients with chronic kidney disease. Kim, SM., Lee, CH., Oh, YK., et al.[2019]

Iron deficiency is a significant issue for individuals with chronic kidney disease, leading to anemia, and both oral and intravenous (i.v.) iron treatments are available to address this deficiency.

Recent studies suggest that more aggressive iron repletion in patients with chronic kidney disease who require kidney replacement therapy can improve anemia management and may positively impact serious health outcomes like cardiovascular disease and survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Iron Deficiency Anemia in CKD and End-Stage Kidney Disease. Gutiérrez, OM.[2023]

In a study of 60 adults with moderate to severe chronic kidney disease (CKD), ferric citrate was found to significantly increase transferrin saturation (TSAT) and ferritin levels compared to ferrous sulfate over a 12-week period.

Both treatments had similar safety profiles, with no significant differences in adverse events, indicating that ferric citrate is a safe and effective alternative for treating iron deficiency in CKD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Ferric Citrate versus Ferrous Sulfate on Iron and Phosphate Parameters in Patients with Iron Deficiency and CKD: A Randomized Trial. Womack, R., Berru, F., Panwar, B., et al.[2023]

In a randomized double-blind trial involving 232 adults with nondialysis-dependent chronic kidney disease (NDD-CKD) and iron deficiency anemia, oral ferric citrate significantly increased hemoglobin levels compared to placebo, with 52.1% of patients achieving a ≥1.0 g/dl increase in hemoglobin (P<0.001).

Ferric citrate was found to be safe, with similar rates of serious adverse events (12.0% for ferric citrate vs. 11.2% for placebo), although gastrointestinal issues like diarrhea and constipation were more common in the ferric citrate group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Ferric Citrate in Patients with Nondialysis-Dependent CKD and Iron Deficiency Anemia. Fishbane, S., Block, GA., Loram, L., et al.[2018]

Oral iron supplementation with ferrous sulfate (FeSO₄) leads to significantly higher levels of non-transferrin-bound iron (NTBI) in the bloodstream compared to other iron compounds, which raises safety concerns for young children with malaria.

In contrast, iron compounds like sodium iron ethylenediaminetetraacetic acid (NaFeEDTA) and iron polymaltose show negligible NTBI responses, suggesting they may be safer alternatives for iron supplementation in areas where malaria is prevalent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral administration of ferrous sulfate, but not of iron polymaltose or sodium iron ethylenediaminetetraacetic acid (NaFeEDTA), results in a substantial increase of non-transferrin-bound iron in healthy iron-adequate men. Schümann, K., Solomons, NW., Romero-Abal, ME., et al.[2022]

Iron deficiency is a significant contributor to anemia in individuals with chronic kidney disease, and recent advancements in oral and intravenous iron therapies have improved treatment options, including better tolerated oral agents like ferric citrate and ferric maltol.

New intravenous iron therapies, such as ferric carboxymaltose, reduce the number of required infusions and the risk of serious allergic reactions, but they may pose risks for conditions like 6H syndrome, which involves multiple metabolic disturbances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent and Emerging Therapies for Iron Deficiency in Anemia of CKD: A Review. Bazeley, JW., Wish, JB.[2022]

A superpharmacologic dose of iron sulfate (260 mg elemental iron) taken on an empty stomach resulted in significant iron absorption in chronic peritoneal dialysis patients, with a 105% increase in serum iron levels at 2 hours.

While the increase in serum iron was lower in dialysis patients compared to healthy controls, none of the dialysis patients experienced gastrointestinal side effects, suggesting this method could be a safe and effective way to supplement iron in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iron absorption after single pharmacological oral iron loading test in patients on chronic peritoneal dialysis and in healthy volunteers. Bastani, B., Islam, S., Boroujerdi, N.[2020]

In a study of 49,943 US Veterans with chronic kidney disease, oral iron replacement therapy (IRT) did not reduce the risk of progressing to end-stage kidney disease (ESKD) and was linked to a higher risk of all-cause mortality overall.

However, in patients with anemia and hemoglobin levels below 10 g/dL, oral IRT was associated with significantly lower mortality, suggesting that its benefits may be limited to specific patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of oral iron replacement therapy with kidney failure and mortality in CKD patients. Paul, S., Shrestha, P., Sumida, K., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

A randomized trial of intravenous and oral iron in chronic kidney disease. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Erythropoietic response to oral iron in patients with nondialysis-dependent chronic kidney disease in the FIND-CKD trial . [2018]

3. England pubmed.ncbi.nlm.nih.gov

Intravenous iron administration strategies and anemia management in hemodialysis patients. [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

The effects of oral iron supplementation on the progression of anemia and renal dysfunction in patients with chronic kidney disease. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Treatment of Iron Deficiency Anemia in CKD and End-Stage Kidney Disease. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Effect of Ferric Citrate versus Ferrous Sulfate on Iron and Phosphate Parameters in Patients with Iron Deficiency and CKD: A Randomized Trial. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Effects of Ferric Citrate in Patients with Nondialysis-Dependent CKD and Iron Deficiency Anemia. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Oral administration of ferrous sulfate, but not of iron polymaltose or sodium iron ethylenediaminetetraacetic acid (NaFeEDTA), results in a substantial increase of non-transferrin-bound iron in healthy iron-adequate men. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Recent and Emerging Therapies for Iron Deficiency in Anemia of CKD: A Review. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Iron absorption after single pharmacological oral iron loading test in patients on chronic peritoneal dialysis and in healthy volunteers. [2020]

11. England pubmed.ncbi.nlm.nih.gov

Association of oral iron replacement therapy with kidney failure and mortality in CKD patients. [2023]

12. Germany pubmed.ncbi.nlm.nih.gov

The therapeutic equivalence of oral and intravenous iron in renal dialysis patients. [2013]