Intravenous Versus Oral Iron Therapy in Hemodialysis Patients

Study Overview
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Brief Summary
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This study is aim to compare the efficacy of intravenous versus oral iron therapy regarding the hemoglobin levels, iron status and erythropoietin dosage in maintenance hemodialysis patients

Detailed Description
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Run-in phase: All eligible patients will enter run-in phase for 2 weeks. In this phase, all oral therapy that patients received before enrolment into the study will be discontinued. Masking: Opened label Allocation: Block of four randomization into 2 treatment arms: intravenous iron and oral iron Safety criteria: Study participants who meet the following criteria will be discontinued from the study. All patients data will be analyzed according to intention-to-treat principles. Hemoglobin levels < 6.0 g/dl Packed red cells transfusion is required Serum ferritin >1,000 md/dl

Official Title
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Effects Intravenous Iron and Oral Iron Therapy on Erythropoietin Dose in Maintenance Hemodialysis Patients: An Open-label, Randomized, Controlled Study

Conditions
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Hemodialysis Complication, Anemia, Iron Deficiency Anemia

Intervention / Treatment
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* Drug: Intravenous iron
* Drug: Oral iron


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years Hemodialysis for at least 3 months Hemoglobin levels between 8 and 11.5 g/dl inclusive Transferrin saturation (TSAT) <50% and ferritin <800 mg/dl Stable dose of epoetin of any types and iron therapy for at least 1 month Exclusion Criteria: History of iron allergy Pregnant or lactating women Patients with known hematologic disorders other than anemia of renal disease and iron deficiency anemia Patients with hemoglobinopathy e.g., thalassemia Patients with iron overload or hemochromatosis Patients with gastrointestinal hemorrhage during 6 months before enrolment in to the study Patients with current severe infection Patients with any malignancies Patients with severe psychiatric illness Patients with any other medical condition which, in the Investigator's judgment, may be associated with increased risk to the subject or may interfere with study assessments or outcomes Patients who currently receive medications that can altered gastrointestinal absorption of oral iron e.g., aluminum carbonate, aluminum hydroxide, chloramphenicol, dimercaprol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Maintenance hemodialysis patients who are eligible to enrol into the study according to inclusion and exclusion criteria will be start with 2-week run-in period before randomization. During this run-in period, all iron supplements that patients receive including oral and intravenous iron will be discontinued.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous iron<br>Iron sucrose 200 mg every 2 weeks Folic acid 5 mg/day B6 10 mg/day | Drug: Intravenous iron<br>* Iron sucrose will be given by continuous infusion for 1 hour during the last 1 hour of dialysis session. Iron sucrose will be given for 24 weeks during study period. Serum ferritin will be monitored at 4, 12, and 24 weeks after randomization. The dosage of intravenous iron will be adjusted according to serum ferritin levels as follows. Serum ferritin <500 mg/dl: iron sucrose 100 mg every 2 weeks Serum ferritin 500-800 mg/dl: iron sucrose 100 mg every 4 weeks Serum ferritin >800 mg/dl: discontinue iron sucrose<br>* Other names: Venofer, Encifer;|
| Active Comparator: Oral iron<br>Ferrous fumarate 600 mg/day Folic acid 6.5 mg/day B6 15 mg/day | Drug: Oral iron<br>* 1 tablet, three times a day, of iron fumarate will be prescribed for 24 weeks of study period. The dosage of iron fumarate will be adjusted according to serum ferritin levels as follows. Serum ferritin will be monitored at 4, 12, and 24 weeks after randomization. Serum ferritin <500 mg/dl: iron fumarate 200 mg three times daily Serum ferritin 500-800 mg/dl: iron fumarate 200 mg once daily Serum ferritin >800 mg/dl: discontinue iron fumarate<br>* Other names: Ferli-6 (ferrous fumarate 200 mg, folic acid 0.5 mg, B6 5 mg);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of epoetin dose | Hemoglobin levels will be monitored and epoetin dose will be adjusted according to hemoglobin levels at 4, 12, 24 weeks after randomization. Protocols for epoetin dose adjustments are shown as follow. Hemoglobin levels (g/dl) Epoetin dose adjustment <9.0 Increased by 50% 9.0 to <10.0 Increased by 25% 10.0 to <11.5 No change 11.5 to <12.5 Decreased by 25% 12.5 Decreased by 50% | 24 weeks after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin levels | Levels of hemoglobin concentration | 4, 12, 24 weeks after randomization | 
| Erythropoietin resistance index | Erythropoietin resistance index is calculated as the mean weekly epoetin dose per kg body weight divided by the average hemoglobin level | 4, 12, 24 weeks after randomization | 
| Major cardiovascular events (MACE) | Major adverse cardiovascular events (MACE) is defined as a composite of nonfatal stroke, Nonfatal myocardial infarction, and cardiovascular death | 24-week period after randomization | 
| Unscheduled hospitalization | Numbers of any hospitalizations that is not planned | 24-week period after randomization | 
| Hospitalization due to infections | Numbers of any hospitalizations that is caused by infections | 24-week period after randomization | 
| C-reactive protein (CRP) | Serum levels of high sensitivity c-reactive protein | 4, 12, 24 weeks after randomization | 
| The kidney disease quality of life (KDQOL) instrument | Quality of life will be assessed by the kidney disease quality of life (KDQOL) instrument | 4, 12, 24 weeks after randomization | 
| Quality of life will be assessed by EQ-5D-5L (EuroQol - 5 Dimensions - 5 Levels) | EQ-5D-5L is the instrument used to evaluate health-related quality of life states in adults, consisting of five dimensions (Mobility, Self-care, Usual activities, Pain & discomfort, Anxiety & depression), each of which has five severity levels | 4, 12, 24 weeks after randomization | 
| Cost-effectiveness of iron therapy | The cost of iron therapy compared with the cost of epoetin | 4, 12, 24 weeks after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Iron therapy, Hemodialysis, Iron status, Epoetin dose, Intravenous iron, Oral iron