Intravenous Versus Oral Iron Therapy in Hemodialysis Patients (IVO-IRON)

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

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

Study Overview

• Status: Unknown
• Conditions: Anemia; Hemodialysis Complication; Iron Deficiency Anemia
• Intervention / Treatment: Drug: Intravenous iron; Drug: Oral iron

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 124
• Phase: Phase 3

Contacts and Locations

Study Locations

• Thailand
  • Chiang Mai, Thailand, 50200
    • Recruiting
    • Chiang Mai University Hospital, Faculty of Medicine, Chiang Mai University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous iron; Iron sucrose 200 mg every 2 weeks Folic acid 5 mg/day B6 10 mg/day	Drug: Intravenous iron; 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; Other Names: Venofer, Encifer
Active Comparator: Oral iron; Ferrous fumarate 600 mg/day Folic acid 6.5 mg/day B6 15 mg/day	Drug: Oral iron; 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; Other Names: Ferli-6 (ferrous fumarate 200 mg, folic acid 0.5 mg, B6 5 mg)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Chiang Mai University

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2020
• Primary Completion (Anticipated): January 31, 2021
• Study Completion (Anticipated): July 31, 2022

Study Registration Dates

• First Submitted: July 6, 2020
• First Submitted That Met QC Criteria: July 8, 2020
• First Posted (Actual): July 9, 2020

Study Record Updates

• Last Update Posted (Actual): August 11, 2020
• Last Update Submitted That Met QC Criteria: August 7, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Hemodialysis; Iron therapy; Intravenous iron; Iron status; Oral iron; Epoetin dose
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Iron Metabolism Disorders; Anemia, Iron-Deficiency; Anemia; Physiological Effects of Drugs; Trace Elements; Micronutrients; Vitamins; Vitamin B Complex; Hematinics; Ferrous fumarate; Folic Acid; Iron
• Other Study ID Numbers: MED-2563-07092

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Request for individual participant data (IPD) has to be submitted to the Institutional Review Board (IRB) of Faculty of Medicine, Chiang Mai University, Chiang Mai, THAILAND.

Drug and device information, study documents

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