A Study Comparing the Iron Substitution With the Medicinal Products Ferinject or Monofer (HOMe_aFers_1)

A Randomized, Double-blind Comparative Study Comparing Ferric Carboxymaltose (Ferinject) and Iron Isomaltoside 1000 (Monofer) for Iron Substitution in Iron-deficiency Anemia

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.

Study Overview

• Status: Completed
• Conditions: Anemia, Iron-Deficiency
• Intervention / Treatment: Drug: Iron Isomaltoside 1000; Drug: Ferric Carboxymaltose

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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Saarland
    • Homburg, Saarland, Germany, 66421
      • Universitätsklinikum des Saarlandes

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Iron Isomaltoside 1000; 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.	Drug: Iron Isomaltoside 1000; Other Names: Monofer
Active Comparator: Ferric Carboxymaltose; 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.	Drug: Ferric Carboxymaltose; Other Names: Ferinject

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of hypophosphatemia	The incidence of hypophosphatemia is defined as a drop of serum phosphate below 2.0 mg/dl.	From baseline to day 35

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of plasma phosphate concentrations.		From baseline to day 35
Changes of fractional Phosphate urinary excretion.		From baseline to day 35
Changes of Plasma Vitamin D (active, inactive).		From baseline to day 35
Changes of fibroblast growth factor 23 (intact and c-terminal).		From baseline to day 35
Changes of parathyroid Hormone.		From baseline to day 35
Changes of Plasma calcium.		From baseline to day 35
Changes of Plasma alkaline Phosphatase.		From baseline to day 35
Changes of Plasma soluble Klotho.		From baseline to day 35
Changes of Plasma Hepcidin-25.		From baseline to day 35
Changes of Serum N-Terminal Propeptide of Type I Collagen (PINP).		From baseline to day 35
Changes of Pyridinoline (PYD) in the urine		From baseline to day 35
Changes of Quality of life.	German Version of the Short Form (36) Health Survey by Matthias Morfeld, Inge Kirchberger, Monika Bullinger.	From baseline to day 35
Incidence of (supra)ventricular cardiac arrhythmias in the ambulatory Electrocardiography.		Before and 7 days after administration of iron compound
Changes of QT-time in the 12-lead Electrocardiography.		From baseline to day 35
Changes of QT-Dispersion in the 12-lead Electrocardiography.		From baseline to day 35
Changes of Left Ventricular Mass Index	Echocardiographic measurement	From baseline to day 7
Count of monocyte subpopulations.	Count of classical , intermediate and nonclassical monocytes using flow cytometry.	Right before the singular infusion of the iron compound is started and right after infusion of the iron compound is completed.
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.	Right before the singular infusion of the iron compound is started and right after the infusion of iron compound is completed.
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.)	From baseline to day 35
Changes of Left Atrial Volume Index	Echocardiographic measurement	From Baseline to day 7
Changes of Systolic Ejection Fraction	Echocardiographic measurement	From Baseline to day 7
Changes of Diastolic Left Ventricular Function	Echocardiographic measurement	From Baseline to day 7

Collaborators and Investigators

• Sponsor: Universität des Saarlandes
• Investigators: Principal Investigator: Gunnar Heine, MD, Universität Des Saarlandes; Study Director: Danilo Fliser, MD, Universität Des Saarlandes

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (Actual): June 1, 2020
• Study Completion (Actual): June 1, 2020

Study Registration Dates

• First Submitted: September 8, 2016
• First Submitted That Met QC Criteria: September 13, 2016
• First Posted (Estimate): September 19, 2016

Study Record Updates

• Last Update Posted (Actual): November 30, 2020
• Last Update Submitted That Met QC Criteria: November 26, 2020
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Iron; anemia; phosphorus; FGF-23
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Iron Metabolism Disorders; Anemia, Iron-Deficiency; Anemia; Hematinics; Iron isomaltoside 1000
• Other Study ID Numbers: P-0101; 2015-004808-36 (EudraCT Number); U1111-1176-4563 (Registry Identifier: WHO Universal Trial Number); DRKS00010766 (Registry Identifier: Deutsches Register Klinischer Studien)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No