Clinical trial NCT02905539: A Study Comparing the Iron Substitution With the Medicinal Products Ferinject or Monofer
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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Anemia, Iron-Deficiency
Keywords: Iron
anemia
phosphorus
FGF-23
Lead sponsor: Universität des Saarlandes
Sponsor class: OTHER
First posted: 2016-09-19
Enrollment: 26
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Incidence of hypophosphatemia
timeFrame: From baseline to day 35
Secondary outcomes:
measure: Changes of plasma phosphate concentrations.
timeFrame: From baseline to day 35
measure: Changes of fractional Phosphate urinary excretion.
timeFrame: From baseline to day 35
measure: Changes of Plasma Vitamin D (active, inactive).
timeFrame: From baseline to day 35
measure: Changes of fibroblast growth factor 23 (intact and c-terminal).
timeFrame: From baseline to day 35
measure: Changes of parathyroid Hormone.
timeFrame: From baseline to day 35
measure: Changes of Plasma calcium.
timeFrame: From baseline to day 35
measure: Changes of Plasma alkaline Phosphatase.
timeFrame: From baseline to day 35
measure: Changes of Plasma soluble Klotho.
timeFrame: From baseline to day 35
measure: Changes of Plasma Hepcidin-25.
timeFrame: From baseline to day 35
measure: Changes of Serum N-Terminal Propeptide of Type I Collagen (PINP).
timeFrame: From baseline to day 35
measure: Changes of Pyridinoline (PYD) in the urine
timeFrame: From baseline to day 35
measure: Changes of Quality of life.
timeFrame: From baseline to day 35
measure: Incidence of (supra)ventricular cardiac arrhythmias in the ambulatory Electrocardiography.
timeFrame: Before and 7 days after administration of iron compound
measure: Changes of QT-time in the 12-lead Electrocardiography.
timeFrame: From baseline to day 35
measure: Changes of QT-Dispersion in the 12-lead Electrocardiography.
timeFrame: From baseline to day 35
measure: Changes of Left Ventricular Mass Index
timeFrame: From baseline to day 7
measure: Count of monocyte subpopulations.
timeFrame: Right before the singular infusion of the iron compound is started and right after infusion of the iron compound is completed.
measure: Measurement of phagocytic capacity of monocytes.
timeFrame: Right before the singular infusion of the iron compound is started and right after the infusion of iron compound is completed.
measure: Changes of fatigue
timeFrame: From baseline to day 35
measure: Changes of Left Atrial Volume Index
timeFrame: From Baseline to day 7
measure: Changes of Systolic Ejection Fraction
timeFrame: From Baseline to day 7
measure: Changes of Diastolic Left Ventricular Function
timeFrame: From Baseline to day 7
Other outcomes:
Locations:
city: Homburg
country: Germany
facility: Universitätsklinikum des Saarlandes
state: Saarland
Study officials:
affiliation: Universität des Saarlandes
name: Gunnar Heine, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universität des Saarlandes
name: Danilo Fliser, MD
role: STUDY_DIRECTOR
References:
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.