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

• ClinicalTrials.gov Identifier: NCT02905539
• Recruitment Status: Completed
• First Posted: September 19, 2016
• Last Update Posted: November 30, 2020
• Sponsor: Universität des Saarlandes
• Information provided by (Responsible Party): Universität des Saarlandes

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.

Condition or disease	Intervention/treatment	Phase
Anemia, Iron-Deficiency	Drug: Iron Isomaltoside 1000; Drug: Ferric Carboxymaltose	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Start Date: July 2016
• Actual Primary Completion Date: June 2020
• Actual Study Completion Date: June 2020

Arms and Interventions

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 Name: 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 Name: Ferinject

Outcome Measures

Primary Outcome Measures :

1. Incidence of hypophosphatemia [ Time Frame: From baseline to day 35 ]
   The incidence of hypophosphatemia is defined as a drop of serum phosphate below 2.0 mg/dl.

Secondary Outcome Measures :

1. Changes of plasma phosphate concentrations. [ Time Frame: From baseline to day 35 ]
2. Changes of fractional Phosphate urinary excretion. [ Time Frame: From baseline to day 35 ]
3. Changes of Plasma Vitamin D (active, inactive). [ Time Frame: From baseline to day 35 ]
4. Changes of fibroblast growth factor 23 (intact and c-terminal). [ Time Frame: From baseline to day 35 ]
5. Changes of parathyroid Hormone. [ Time Frame: From baseline to day 35 ]
6. Changes of Plasma calcium. [ Time Frame: From baseline to day 35 ]
7. Changes of Plasma alkaline Phosphatase. [ Time Frame: From baseline to day 35 ]
8. Changes of Plasma soluble Klotho. [ Time Frame: From baseline to day 35 ]
9. Changes of Plasma Hepcidin-25. [ Time Frame: From baseline to day 35 ]
10. Changes of Serum N-Terminal Propeptide of Type I Collagen (PINP). [ Time Frame: From baseline to day 35 ]
11. Changes of Pyridinoline (PYD) in the urine [ Time Frame: From baseline to day 35 ]
12. Changes of Quality of life. [ Time Frame: From baseline to day 35 ]
    German Version of the Short Form (36) Health Survey by Matthias Morfeld, Inge Kirchberger, Monika Bullinger.
13. Incidence of (supra)ventricular cardiac arrhythmias in the ambulatory Electrocardiography. [ Time Frame: Before and 7 days after administration of iron compound ]
14. Changes of QT-time in the 12-lead Electrocardiography. [ Time Frame: From baseline to day 35 ]
15. Changes of QT-Dispersion in the 12-lead Electrocardiography. [ Time Frame: From baseline to day 35 ]
16. Changes of Left Ventricular Mass Index [ Time Frame: From baseline to day 7 ]
    Echocardiographic measurement
17. Count of monocyte subpopulations. [ Time Frame: Right before the singular infusion of the iron compound is started and right after infusion of the iron compound is completed. ]
    Count of classical , intermediate and nonclassical monocytes using flow cytometry.
18. Measurement of phagocytic capacity of monocytes. [ Time Frame: Right before the singular infusion of the iron compound is started and right after the infusion of iron compound is completed. ]
    Exposition of Monocytes to Fluoresbrite Yellow Green (YG) Carboxylate Microspheres and subsequent flow cytometric count of Fluorescein isothiocyanate-positive Monocytes.
19. Changes of fatigue [ Time Frame: From baseline to day 35 ]
    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.)
20. Changes of Left Atrial Volume Index [ Time Frame: From Baseline to day 7 ]
    Echocardiographic measurement
21. Changes of Systolic Ejection Fraction [ Time Frame: From Baseline to day 7 ]
    Echocardiographic measurement
22. Changes of Diastolic Left Ventricular Function [ Time Frame: From Baseline to day 7 ]
    Echocardiographic measurement

Eligibility Criteria

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

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.

Contacts and Locations

Locations

Germany

Universitätsklinikum des Saarlandes

Homburg, Saarland, Germany, 66421

Sponsors and Collaborators

Universität des Saarlandes

Investigators

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Universität des Saarlandes
• ClinicalTrials.gov Identifier: NCT02905539
• 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 )
• First Posted: September 19, 2016
• Last Update Posted: November 30, 2020
• Last Verified: April 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Universität des Saarlandes:

Iron; anemia; phosphorus; FGF-23

Additional relevant MeSH terms:

Anemia; Anemia, Iron-Deficiency; Hematologic Diseases; Anemia, Hypochromic; Iron Metabolism Disorders; Metabolic Diseases; Iron isomaltoside 1000; Hematinics