IVO-IRON: Intravenous Versus Oral Iron Therapy in Hemodialysis Patients

Sponsor

Chiang Mai University (Other)

Overall Status

Unknown status

CT.gov ID

NCT04464850

Collaborator

(none)

124

Enrollment

Location

Arms

Anticipated Duration (Months)

5.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Hemodialysis Complication Anemia Iron Deficiency Anemia	Drug: Intravenous iron Drug: Oral iron	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

124 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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.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 (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 29, 2020

Anticipated Primary Completion Date :

Jan 31, 2021

Anticipated Study Completion Date :

Jul 31, 2022

Arms and Interventions

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)

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)

Outcome Measures

Primary Outcome Measures

Changes of epoetin dose [24 weeks after randomization]
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%

Secondary Outcome Measures

Hemoglobin levels [4, 12, 24 weeks after randomization]
Levels of hemoglobin concentration
Erythropoietin resistance index [4, 12, 24 weeks after randomization]
Erythropoietin resistance index is calculated as the mean weekly epoetin dose per kg body weight divided by the average hemoglobin level
Major cardiovascular events (MACE) [24-week period after randomization]
Major adverse cardiovascular events (MACE) is defined as a composite of nonfatal stroke, Nonfatal myocardial infarction, and cardiovascular death
Unscheduled hospitalization [24-week period after randomization]
Numbers of any hospitalizations that is not planned
Hospitalization due to infections [24-week period after randomization]
Numbers of any hospitalizations that is caused by infections
C-reactive protein (CRP) [4, 12, 24 weeks after randomization]
Serum levels of high sensitivity c-reactive protein
The kidney disease quality of life (KDQOL) instrument [4, 12, 24 weeks after randomization]
Quality of life will be assessed by the kidney disease quality of life (KDQOL) instrument
Quality of life will be assessed by EQ-5D-5L (EuroQol - 5 Dimensions - 5 Levels) [4, 12, 24 weeks after randomization]
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
Cost-effectiveness of iron therapy [4, 12, 24 weeks after randomization]
The cost of iron therapy compared with the cost of epoetin

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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