A Study Comparing the Iron Substitution With the Medicinal Products Ferinject or Monofer (HOMe_aFers_1)
Primary Purpose
Anemia, Iron-Deficiency
Status
Completed
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
Iron Isomaltoside 1000
Ferric Carboxymaltose
Sponsored by
About this trial
This is an interventional treatment trial for Anemia, Iron-Deficiency focused on measuring Iron, anemia, phosphorus, FGF-23
Eligibility Criteria
Inclusion Criteria:
- written informed consent,
- female,
- gynecological blood losses,
- age ≥ 18 years,
- iron deficiency anemia,
- Hemoglobin < 12,0 g/dl,
- Serum-Ferritin ≤ 100 ng/ml or Serum-Ferritin ≤ 300 ng/ml and Transferrin-saturation ≤ 30 %,
- Intolerance to or inefficacy of an oral iron supplement
- estimated Glomerular Filtration Rate > 15 ml/min/1.73 m²
Exclusion Criteria:
- known hypersensitivity to MonoFer® or FERINJECT®,
- severe, known hypersensitivity to other intravenous iron preparations,
- Plasma Phosphate < 2.5 mg/dl at screening,
- Hemochromatosis,
- Untreated hyperparathyroidism,
- Renal replacement therapy/kidney transplantation,
- Active malignant disease, disease-free survival for less than 5 years,
- Intravenous iron administration within the last 30 days,
- Treatment with erythropoietin or erythropoietin-stimulating agents, transfusion of red blood cells, radiotherapy or chemotherapy within the last 60 days,
- Surgery under anesthetic within the last 10 days,
- Alanine transaminase (ALT) or aspartate transaminase (AST) > 1.5 fold above levels in healthy individuals,
- Acute febrile infections within the last 7 days,
- Chronic inflammatory diseases requiring a systemic antiinflammatory treatment,
- self-reported severe asthma or eczema,
- presence of relative contraindications (any allergy, any immunologic or inflammatory disease, history of atopic allergies), for which a treatment with the medicinal investigational products is not deemed indicated by the investigator,
- pregnancy,
- women of childbearing potential without an effective method of contraception,
- lactating women,
- Present alcohol or drug dependency,
- Patients with a history of a psychological illness or seizures,
- Non-compliance or administration of any investigational drug within 30 days preceding the study start.
Sites / Locations
- Universitätsklinikum des Saarlandes
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Iron Isomaltoside 1000
Ferric Carboxymaltose
Arm Description
Subjects receive Iron Isomaltoside 1000 solution intravenously. Dosage: A unique dose of 20 mg per kilogram bodyweight, but total dose is not more than 1000 mg.
Subjects receive Ferric Carboxymaltose solution intravenously. Dosage: A unique dose of 20 mg per kilogram bodyweight, but total dose is not more than 1000 mg.
Outcomes
Primary Outcome Measures
Incidence of hypophosphatemia
The incidence of hypophosphatemia is defined as a drop of serum phosphate below 2.0 mg/dl.
Secondary Outcome Measures
Changes of plasma phosphate concentrations.
Changes of fractional Phosphate urinary excretion.
Changes of Plasma Vitamin D (active, inactive).
Changes of fibroblast growth factor 23 (intact and c-terminal).
Changes of parathyroid Hormone.
Changes of Plasma calcium.
Changes of Plasma alkaline Phosphatase.
Changes of Plasma soluble Klotho.
Changes of Plasma Hepcidin-25.
Changes of Serum N-Terminal Propeptide of Type I Collagen (PINP).
Changes of Pyridinoline (PYD) in the urine
Changes of Quality of life.
German Version of the Short Form (36) Health Survey by Matthias Morfeld, Inge Kirchberger, Monika Bullinger.
Incidence of (supra)ventricular cardiac arrhythmias in the ambulatory Electrocardiography.
Changes of QT-time in the 12-lead Electrocardiography.
Changes of QT-Dispersion in the 12-lead Electrocardiography.
Changes of Left Ventricular Mass Index
Echocardiographic measurement
Count of monocyte subpopulations.
Count of classical , intermediate and nonclassical monocytes using flow cytometry.
Measurement of phagocytic capacity of monocytes.
Exposition of Monocytes to Fluoresbrite Yellow Green (YG) Carboxylate Microspheres and subsequent flow cytometric count of Fluorescein isothiocyanate-positive Monocytes.
Changes of fatigue
The German Version of the Multidimensional Fatigue Inventory. (Smets E. M. A., Garssen B., Bonke B. and Haes de J. C. J. M. (1995). The Multidimensional Fatigue Inventory (MFI); Psychometric qualities of an instrument to assess fatigue. Journal of Psychosomatic Research, 39, 315-325.)
Changes of Left Atrial Volume Index
Echocardiographic measurement
Changes of Systolic Ejection Fraction
Echocardiographic measurement
Changes of Diastolic Left Ventricular Function
Echocardiographic measurement
Full Information
NCT ID
NCT02905539
First Posted
September 8, 2016
Last Updated
November 26, 2020
Sponsor
Universität des Saarlandes
1. Study Identification
Unique Protocol Identification Number
NCT02905539
Brief Title
A Study Comparing the Iron Substitution With the Medicinal Products Ferinject or Monofer
Acronym
HOMe_aFers_1
Official Title
A Randomized, Double-blind Comparative Study Comparing Ferric Carboxymaltose (Ferinject) and Iron Isomaltoside 1000 (Monofer) for Iron Substitution in Iron-deficiency Anemia
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
July 2016 (undefined)
Primary Completion Date
June 2020 (Actual)
Study Completion Date
June 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universität des Saarlandes
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine to what extend a treatment with the iron compounds Iron Isomaltoside 1000 or Ferric Carboxymaltose is leading to hypophosphatemia and to study the potential clinical impact of hypophosphatemia.
Detailed Description
Recent studies suggested that intravenous iron preparations for anemia treatment may have adverse effects on phosphorus regulation, as they may induce an increase in the phosphaturic hormone Fibroblast Growth Factor-23 (FGF-23) and a subsequent fall in plasma phosphorus levels.
So far it is unknown if these effects are class- or substance-specific.
This study will address the question whether among female participants with iron deficiency anemia the application of ferric-(III)-derisomaltose and ferric carboxymaltose will cause episodes of hypophosphatemia to same extend. The investigators will additionally compare the effects of the two iron preparations on other parameters of calcium-phosphate metabolism, and decipher potential consequences of hypophosphatemia by analysing cardiac function, immunological parameters and quality of life.
In order to investigate these outcomes, 60 women with iron deficient anemia will be randomised to receive either ferric-(III)-derisomaltose or ferric carboxymaltose.
The monocentric study will be conducted at Saarland University Medical Center. For each participating woman, the study comprises five visits to the study center during a period of five weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia, Iron-Deficiency
Keywords
Iron, anemia, phosphorus, FGF-23
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
26 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Iron Isomaltoside 1000
Arm Type
Experimental
Arm Description
Subjects receive Iron Isomaltoside 1000 solution intravenously. Dosage: A unique dose of 20 mg per kilogram bodyweight, but total dose is not more than 1000 mg.
Arm Title
Ferric Carboxymaltose
Arm Type
Active Comparator
Arm Description
Subjects receive Ferric Carboxymaltose solution intravenously. Dosage: A unique dose of 20 mg per kilogram bodyweight, but total dose is not more than 1000 mg.
Intervention Type
Drug
Intervention Name(s)
Iron Isomaltoside 1000
Other Intervention Name(s)
Monofer
Intervention Type
Drug
Intervention Name(s)
Ferric Carboxymaltose
Other Intervention Name(s)
Ferinject
Primary Outcome Measure Information:
Title
Incidence of hypophosphatemia
Description
The incidence of hypophosphatemia is defined as a drop of serum phosphate below 2.0 mg/dl.
Time Frame
From baseline to day 35
Secondary Outcome Measure Information:
Title
Changes of plasma phosphate concentrations.
Time Frame
From baseline to day 35
Title
Changes of fractional Phosphate urinary excretion.
Time Frame
From baseline to day 35
Title
Changes of Plasma Vitamin D (active, inactive).
Time Frame
From baseline to day 35
Title
Changes of fibroblast growth factor 23 (intact and c-terminal).
Time Frame
From baseline to day 35
Title
Changes of parathyroid Hormone.
Time Frame
From baseline to day 35
Title
Changes of Plasma calcium.
Time Frame
From baseline to day 35
Title
Changes of Plasma alkaline Phosphatase.
Time Frame
From baseline to day 35
Title
Changes of Plasma soluble Klotho.
Time Frame
From baseline to day 35
Title
Changes of Plasma Hepcidin-25.
Time Frame
From baseline to day 35
Title
Changes of Serum N-Terminal Propeptide of Type I Collagen (PINP).
Time Frame
From baseline to day 35
Title
Changes of Pyridinoline (PYD) in the urine
Time Frame
From baseline to day 35
Title
Changes of Quality of life.
Description
German Version of the Short Form (36) Health Survey by Matthias Morfeld, Inge Kirchberger, Monika Bullinger.
Time Frame
From baseline to day 35
Title
Incidence of (supra)ventricular cardiac arrhythmias in the ambulatory Electrocardiography.
Time Frame
Before and 7 days after administration of iron compound
Title
Changes of QT-time in the 12-lead Electrocardiography.
Time Frame
From baseline to day 35
Title
Changes of QT-Dispersion in the 12-lead Electrocardiography.
Time Frame
From baseline to day 35
Title
Changes of Left Ventricular Mass Index
Description
Echocardiographic measurement
Time Frame
From baseline to day 7
Title
Count of monocyte subpopulations.
Description
Count of classical , intermediate and nonclassical monocytes using flow cytometry.
Time Frame
Right before the singular infusion of the iron compound is started and right after infusion of the iron compound is completed.
Title
Measurement of phagocytic capacity of monocytes.
Description
Exposition of Monocytes to Fluoresbrite Yellow Green (YG) Carboxylate Microspheres and subsequent flow cytometric count of Fluorescein isothiocyanate-positive Monocytes.
Time Frame
Right before the singular infusion of the iron compound is started and right after the infusion of iron compound is completed.
Title
Changes of fatigue
Description
The German Version of the Multidimensional Fatigue Inventory. (Smets E. M. A., Garssen B., Bonke B. and Haes de J. C. J. M. (1995). The Multidimensional Fatigue Inventory (MFI); Psychometric qualities of an instrument to assess fatigue. Journal of Psychosomatic Research, 39, 315-325.)
Time Frame
From baseline to day 35
Title
Changes of Left Atrial Volume Index
Description
Echocardiographic measurement
Time Frame
From Baseline to day 7
Title
Changes of Systolic Ejection Fraction
Description
Echocardiographic measurement
Time Frame
From Baseline to day 7
Title
Changes of Diastolic Left Ventricular Function
Description
Echocardiographic measurement
Time Frame
From Baseline to day 7
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
written informed consent,
female,
gynecological blood losses,
age ≥ 18 years,
iron deficiency anemia,
Hemoglobin < 12,0 g/dl,
Serum-Ferritin ≤ 100 ng/ml or Serum-Ferritin ≤ 300 ng/ml and Transferrin-saturation ≤ 30 %,
Intolerance to or inefficacy of an oral iron supplement
estimated Glomerular Filtration Rate > 15 ml/min/1.73 m²
Exclusion Criteria:
known hypersensitivity to MonoFer® or FERINJECT®,
severe, known hypersensitivity to other intravenous iron preparations,
Plasma Phosphate < 2.5 mg/dl at screening,
Hemochromatosis,
Untreated hyperparathyroidism,
Renal replacement therapy/kidney transplantation,
Active malignant disease, disease-free survival for less than 5 years,
Intravenous iron administration within the last 30 days,
Treatment with erythropoietin or erythropoietin-stimulating agents, transfusion of red blood cells, radiotherapy or chemotherapy within the last 60 days,
Surgery under anesthetic within the last 10 days,
Alanine transaminase (ALT) or aspartate transaminase (AST) > 1.5 fold above levels in healthy individuals,
Acute febrile infections within the last 7 days,
Chronic inflammatory diseases requiring a systemic antiinflammatory treatment,
self-reported severe asthma or eczema,
presence of relative contraindications (any allergy, any immunologic or inflammatory disease, history of atopic allergies), for which a treatment with the medicinal investigational products is not deemed indicated by the investigator,
pregnancy,
women of childbearing potential without an effective method of contraception,
lactating women,
Present alcohol or drug dependency,
Patients with a history of a psychological illness or seizures,
Non-compliance or administration of any investigational drug within 30 days preceding the study start.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gunnar Heine, MD
Organizational Affiliation
Universität des Saarlandes
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Danilo Fliser, MD
Organizational Affiliation
Universität des Saarlandes
Official's Role
Study Director
Facility Information:
Facility Name
Universitätsklinikum des Saarlandes
City
Homburg
State/Province
Saarland
ZIP/Postal Code
66421
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32654663
Citation
Emrich IE, Lizzi F, Siegel JD, Seiler-Mussler S, Ukena C, Kaddu-Mulindwa D, D'Amelio R, Wagenpfeil S, Brandenburg VM, Bohm M, Fliser D, Heine GH. Hypophosphatemia after high-dose iron repletion with ferric carboxymaltose and ferric derisomaltose-the randomized controlled HOMe aFers study. BMC Med. 2020 Jul 13;18(1):178. doi: 10.1186/s12916-020-01643-5.
Results Reference
derived
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A Study Comparing the Iron Substitution With the Medicinal Products Ferinject or Monofer
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