Different Oral Iron Dosing Regimens in Treatment of Iron Deficency Anemia in Patients With Chronic Kidney Disease

Comparing Different Oral Iron Dosing Regimens in Treatment of Iron Deficiency Anemia in Patients With Chronic Kidney Disease

Comparing between the efficacy of alternate day oral iron dose, once daily and thrice daily dose in improving anemia in CKD patients

Study Overview

• Status: Not yet recruiting
• Conditions: CKD
• Intervention / Treatment: Drug: Ferrous sulfate

Detailed Description

Anemia is common in chronic kidney disease (CKD) and has been associated with impaired quality of life, cardiovascular disease (CVD) and mortality.

Iron deficiency is common in patients with CKD and an important modifiable factor in treatment of anemia.

In particular, the Kidney Disease: Improving Global Outcomes (KDIGO) anemia work group guidelines define anemia in CKD as a hemoglobin concentration of <13.0 g/dL in men and <12.0 g/dL in women. The current guidelines recommend trial of iron supplementation in CKD when increase in hemoglobin concentration or decrease in erythropoietin dose is desired and investigations reveal percentage transferrin saturation (%TSAT) ≤ 30% and serum ferritin ≤ 500 ng/ml.

The absorption of iron from gastro-intestinal tract and release of iron from reticuloendothelial cells for erythropoiesis are tightly regulated through hepcidin-ferroportin axis. Hepcidin concentrations increase in response to iron excess and inflammation. CKD is associated with elevated hepcidin and ferritin concentrations due to underlying inflammation, independent of iron status.

Iron-deficiency anemia in individuals with CKD may result from functional iron deficiency, absolute iron deficiency, or both. The factors contributing to functional iron deficiency are chronic inflammation and poor hepcidin clearance seen in CKD, whereas absolute iron deficiency includes poor gastrointestinal (GI) dietary iron absorption and blood loss.

In patients with CKD who are not on dialysis, oral route may be preferred as initial mode of iron supplementation. Oral iron is inexpensive, self-administered, convenient and easily available.

Three different oral iron supplement strategies-once daily, multidose per day, and alternate-day dose-improve hemoglobin (Hgb) and iron indices in patients with iron deficiency anemia and chronic kidney disease (CKD).

Study showed that daily doses of oral iron reduced its absorption by increasing serum hepcidin levels. This study also found that administration of oral iron on alternate days as single doses improved iron absorption.

Theoretically, using lower doses and increasing time interval between consecutive doses might reduce the amount of unabsorbed iron in the gastrointestinal tract resulting in lesser gastrointestinal side effects. However, the major concern with alternate day dosing is that only half the total amount of iron is supplemented per unit time compared to daily dosing.

More recent data suggest that lower doses and infrequent administration may be as effective as the traditional regimen while probably associated with lower rates of adverse effects.

Investigators will investigate the effect of every other day, once daily and three times a day dosing of oral iron formulation on measures of iron sufficiency in patients with stages 2,3 and 4 CKD through a randomized controlled trial.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Farrag S Mohamed, MD; Phone Number: 0201064274671; Email: faragsayed99@gmail.com
• Study Contact Backup: Name: Youmna Refaat, Professor; Email: yomna-rm@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

All adult patients above 18 years old with CKD stages 2,3 and 4

Description

Inclusion Criteria:

• All adult patients above 18 years old with CKD stages 2,3 and 4

Exclusion Criteria:

• CKD stage 5 (eGFR below 15 ).
• Patients with hemolytic anemias.
• Chronic liver diseases .
• Autoimmune diseases.
• Malignancy
• History of blood transfusion last 3 months before the study
• Pregnancy
• Adult polycystic kidney disease ( APCKD)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
patients will receive oral iron in alternate day regimen; 50 patients will receive oral ferrous sulphate in alternate day regimen	Drug: Ferrous sulfate; all patients will receive 200 mg elemental iron (ferrous sulphate)
patients will receive oral iron in single daily dose regimen; 50 patients will receive oral ferrous sulphate in single daily dose regimen	Drug: Ferrous sulfate; all patients will receive 200 mg elemental iron (ferrous sulphate)
patients will receive oral iron in thrice daily dose regimen; 50 patients will receive oral ferrous sulphate in thrice daily dose regimen	Drug: Ferrous sulfate; all patients will receive 200 mg elemental iron (ferrous sulphate)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hemoglobin level by gm/dl	Follow up Hemoglobin level in 3 groups	6 months

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Study Chair: Farrag S Mohamed, Assiut university

Publications and helpful links

General Publications

• Stoffel NU, Cercamondi CI, Brittenham G, Zeder C, Geurts-Moespot AJ, Swinkels DW, Moretti D, Zimmermann MB. Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials. Lancet Haematol. 2017 Nov;4(11):e524-e533. doi: 10.1016/S2352-3026(17)30182-5. Epub 2017 Oct 9.

Helpful Links

• Sood, V., Kamboj, K., Bhatia, P. et al. A randomized trial of once daily versus twice daily dosing of oral iron in CKD. Sci Rep 13, 141 (2023). https://doi.org/10.1038/s41598-022-26589-x

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: June 1, 2024
• First Submitted That Met QC Criteria: July 24, 2024
• First Posted (Actual): July 25, 2024

Study Record Updates

• Last Update Posted (Actual): July 25, 2024
• Last Update Submitted That Met QC Criteria: July 24, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: Oral iron in CKD patients

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No