Iron in Patients With Cardiovascular Disease

Study Overview
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Brief Summary
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It is now recognized that iron deficiency in cardiovascular disease contributes to impaired clinical outcome.

Detailed Description
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The clinical trial is designed as a prospective, multi-centre, double-blind, randomised, controlled, interventional trial to investigate whether a therapy with i.v. iron (iron carboxymaltose) compared to saline can improve functional status across a subset of cardiovascular disease -namely acute myocardial infarction, atrial fibrillation, and heart failure with reduced ejection fraction. Iron administration will be carried out according to summary of product characteristics. Bolus administration (1000 mg) will be followed by an optional administration of 500-1000 mg within the first 4 weeks (up to a total of 2000 mg which is in-label) according to approved dosing rules, followed by administration of 500 mg iron carboxymaltose (over 15 minutes), except when haemoglobin is > 16.0 g/dL or ferritin is > 600 µg/L.

Official Title
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Investigator-initiated, Randomized, Double-blind, Controlled, Multi-center Trial of Intravenous Iron in Patients With Cardiovascular Disease and Concomitant Iron Deficiency

Conditions
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Cardiovascular Diseases, Anemia, Iron-deficiency, Acute Myocardial Infarction, Atrial Fibrillation, Systolic Heart Failure

Intervention / Treatment
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* Drug: Ferric carboxymaltose
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cohort A (acute myocardial infarction): Acute Myocardial Infarction within 10 days (randomization/ first iron supplementation/ MRI must be performed within 10 days after AMI), without prior heart failure (defined as any known previous report of LVEF ≤ 45%) Cohort B (atrial fibrillation): Paroxysmal Atrial fibrillation or persistent AF Cohort C (heart failure): Left-ventricular ejection fraction ≤ 45 % (documented within the last 12 months prior to screening), all NYHA classes allowed Confirmed presence of iron deficiency (ferritin < 100 ng/mL or ferritin 100 - 299 ng/mL with transferrin saturation < 20 %) Haemoglobin ≤ 15.5 g/dL Written informed consent Exclusion Criteria: Evidence of iron overload or disturbances in the utilisation of iron History of severe asthma, eczema or other atopic allergy History of immune or inflammatory conditions (e.g. systemic lupus erythematosus, rheumatoid arthritis) Use of renal replacement therapy Treatment with an erythropoietin stimulating agent (ESA), any i.v. iron and/or a blood transfusion in the previous 4 weeks prior to randomisation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous iron<br>Intravenous iron administration in the form of ferric carboxymaltose will be carried out according to summary of product characteristics. Bolus administration (1000 mg) will be followed by an optional administration of 500-1000 mg within the first 4 weeks (up to a total of 2000 mg which is in-label) according to approved dosing rules, followed by administration of 500 mg ferric carboxymaltose at months 4 and 8, except when haemoglobin is > 16.0 g/dL or ferritin is > 600 µg/L. To avoid unblinding in these patients a saline infusion will be administered. | Drug: Ferric carboxymaltose<br>* Intravenous iron<br>|
| Placebo Comparator: Placebo<br>Administration of i.v. NaCl according to the dosing rules for intravenous iron. | Drug: Saline<br>* Saline application according to dosing rules of iron.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort A: Left-ventricular ejection fraction | Change from baseline to week 16 in left-ventricular ejection fraction as determined by cardiac-MRI | 16 weeks | 
| Cohort B: Burden of atrial fibrillation | Delta between treatment groups in burden of atrial fibrillation from day 90 to 365 as assessed by a routinely implanted event recorder. | 12 months | 
| Cohort C: Left-ventricular ejection fraction | Change from baseline to week 16 in left-ventricular ejection fraction as determined by cardiac-MRI. | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Iron deficiency, Atrial fibrillation, Acute myocardial infarction, Systolic heart failure, Anemia