Comparing Reticulocyte Hemoglobin and Transferrin Saturation to Guide Iron Treatment in People on Dialysis

Official title

Efficacy of Reticulocyte Hemoglobin Equivalent-guided Versus Transferrin Saturation-guided Iron Supplement Protocol in Hemodialysis Patients: A Cluster Randomized Controlled Trial

Overview

The goal of this clinical trial is to find out which method is better for guiding iron treatment in adult patients with end-stage kidney disease (ESKD) on hemodialysis who have anemia. The main questions it aims to answer are: Can using reticulocyte hemoglobin equivalent (RET-He) to guide intravenous (IV) iron treatment be as effective as using transferrin saturation (TSAT)? Does the method used to guide iron treatment affect outcomes such as death, heart problems, hospitalizations, infections, or the need for blood transfusions? Researchers will compare RET-He-guided iron treatment with TSAT-guided iron treatment to see if RET-He works just as well and has similar or better outcomes. Participants will: Receive IV iron based on either RET-He or TSAT levels Have blood tests done at the start, 3 months, and 6 months Have their doses of iron and erythropoietin (a medication to treat anemia) adjusted based on the assigned protocol Be monitored for clinical outcomes such as hospitalization, heart events, and infections

Interventions

• Other RET-He-Guided Iron Supplementation
  Participants in this arm will receive intravenous (IV) iron therapy guided by reticulocyte hemoglobin equivalent (RET-He) levels. Iron dosing will follow a protocol based on RET-He values: * RET-He \< 26 pg: IV iron 100 mg weekly * RET-He ≥ 26 pg and \< 30 pg: IV iron 100 mg every 2 weeks * RET-He ≥ 30 pg and ≤ 36 pg: IV iron 100 mg every 4 weeks * RET-He \> 36 pg or ferritin ≥ 800 ng/mL: Discontinue iron supplementation to prevent iron overload
• Other TSAT-Guided Iron Supplementation
  Participants in this arm will receive IV iron therapy guided by transferrin saturation (TSAT) and serum ferritin, as per the Thai Clinical Practice Guidelines for Anemia in CKD (2021). Iron dosing will follow this TSAT-based protocol: * TSAT \< 30% and ferritin \< 200 ng/mL: IV iron 100 mg weekly * TSAT \< 30% and ferritin 200-500 ng/mL: IV iron 100 mg every 2 weeks * TSAT \< 30% and ferritin 500-800 ng/mL or TSAT 30-40%: IV iron 100 mg every 4 weeks * TSAT ≥ 40% or ferritin ≥ 800 ng/mL: Disco
• Other Common
  All participants will receive erythropoiesis-stimulating agents (ESAs) according to a standardized dose adjustment protocol based on hemoglobin levels. Oral iron supplements will be discontinued.

Primary outcome measures

• Erythropoietin resistance index (ERI) [non-inferiority] [Time frame: 6 months]

Secondary outcome measures (5)

• All cause death [Time frame: 6 months]
• Cardiovascular events [Time frame: 6 months]
• Blood Transfusions [Time frame: 6 months]
• Hospitalizations [Time frame: 6 months]
• Incidence of infection [Time frame: 6 months]

Eligibility criteria

Inclusion criteria

• Adult (age 18-80 years)
• ESKD on chronic hemodialysis ≥ 6 months
• EPO therapy ≥ 6 months
• Hb < 13.0 g/dL in male, < 12.0 g/dL in female

Exclusion criteria

• Serum ferritin > 800 ng/mL or TSAT > 40%
• Active infection or malignancy
• Hematologic disease including thalassemia major, hemolysis, myelofibrosis or myelodysplastic disease
• History of marrow suppressive or immunosuppressive medications in past 6 months
• History of active heart failure and recent myocardial infarction /stroke in past 6 months
• History of GI or external bleeding or receiving blood transfusion in past 6 months

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Thailand · 1 center

• King Chulalongkorn Memorial Hospital — Pathumwan

Publications

• Chinudomwong P, Binyasing A, Trongsakul R, Paisooksantivatana K. Diagnostic performance of reticulocyte hemoglobin equivalent in assessing the iron status. J Clin Lab Anal. 2020 Jun;34(6):e23225. doi: 10.1002/jcla.23225. Epub 2020 Feb 11. PMID 32043622
• Susantitaphong P, Siribumrungwong M, Takkavatakarn K, Chongthanakorn K, Lieusuwan S, Katavetin P, Tiranathanagul K, Lekhyananda S, Tungsanga K, Vanichakarn S, Eiam-Ong S, Praditpornsilpa K. Effect of Maintenance Intravenous Iron Treatment on Erythropoietin Dose in Chronic Hemodialysis Patients: A Multicenter Randomized Controlled Trial. Can J Kidney Health Dis. 2020 Jun 19;7:2054358120933397. doi: PMID 32612843
• Babitt JL, Eisenga MF, Haase VH, Kshirsagar AV, Levin A, Locatelli F, Malyszko J, Swinkels DW, Tarng DC, Cheung M, Jadoul M, Winkelmayer WC, Drueke TB; Conference Participants. Controversies in optimal anemia management: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference. Kidney Int. 2021 Jun;99(6):1280-1295. doi: 10.1016/j.kint.2021.03.020. Epub 2021 Apr 8. PMID 33839163
• Wish JB, Anker SD, Butler J, Cases A, Stack AG, Macdougall IC. Iron Deficiency in CKD Without Concomitant Anemia. Kidney Int Rep. 2021 Aug 10;6(11):2752-2762. doi: 10.1016/j.ekir.2021.07.032. eCollection 2021 Nov. PMID 34805628

Identifiers

NCT: NCT06906835 · 0202/67

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗