Effect of Intravenous FerRic carbOxymaltose oN Reverse Remodeling Following Cardiac Resynchronization Therapy

Study Overview
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Brief Summary
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To assess impact on left ventricular reverse remodeling defined as a change in left ventricular ejection fraction in heart failure patients with reduced ejection fraction (and previous implantation of cardiac resynchronization therapy) undergoing treatment with ferric carboxymaltose vs. placebo

Official Title
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Effect of Intravenous FerRic carbOxymaltose oN Reverse Remodeling Following Cardiac Resynchronization Therapy

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: Ferric Carboxymaltose
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic heart failure and implantation of cardiac resynchronization therapy more than 6 months ago and presence of iron deficiency (ferritin < 100 μg/l, irrespective of TSAT or ferritine between 100 - 300 μg/l with TSAT < 20%) and presence of incomplete reverse remodeling (LVEF < 40%). Age ≥18 years Obtained informed consent Stable pharmacological therapy of heart failure during the last 4 weeks (with the exception of diuretics) Exclusion Criteria: Hemochromatosis, iron overload, defined as TSAT > 45% Hemoglobin > 15 g/dl at inclusion Known hypersensitivity to injectafer®. Known active infection, CRP>20 mg/L, clinically significant bleeding, active malignancy. Chronic liver disease and/or screening alanine transaminase (ALT) or aspartate transaminase (AST) above three times the upper limit of the normal range. Immunosuppressive therapy or renal dialysis (current or planned within the next 6 months). History of erythropoietin, i. v. or oral iron therapy, and blood transfusion in previous 12 weeks and/or such therapy planned within the next 6 months. Unstable angina pectoris as judged by the investigator, clinically significant uncorrected valvular disease or left ventricular outflow obstruction, obstructive cardiomyopathy, poorly controlled fast atrial fibrillation or flutter, poorly controlled symptomatic brady- or tachyarrhythmias. Acute myocardial infarction or acute coronary syndrome, transient ischemic attack or stroke within the last 3 months. Coronary-artery bypass graft, percutaneous intervention (e.g. cardiac, cerebrovascular, aortic; diagnostic catheters are allowed) or major surgery, including thoracic and cardiac surgery, within the last 3 months. Inability to fully comprehend and/or perform study procedures in the investigator's opinion. Vitamin B12 and/or serum folate deficiency according to the laboratory (re-screening is possible after substitution therapy). Pregnancy or lactation. Participation in another clinical trial within previous 30 days and/or anticipated participation in another trial during this study. Planned cardiac hospitalization during study follow-up

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Ferric carboxymaltose<br>Ferric carboxymaltose according to SmPC | Drug: Ferric Carboxymaltose<br>* Ferric carboxymaltose will be administered according to product specification dosing<br>* Other names: injectafer;|
| Placebo Comparator: Placebo<br>Normal saline (0.9%) | Drug: Placebo<br>* IV nacl 0.9%<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in left ventricular ejection fraction from baseline | delta_LVEF measured by 3D-echocardiography | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in left ventricular end systolic volume from baseline | delta_LVESV measured by 3D-echocardiography | 3 months | 
| Change in left ventricular end diastolic volume from baseline | delta_LVEDV measured by 3D-echocardiography | 3 months | 
| Force frequency relationship | measured by 2D-echocardiography | 3 months | 
| Heart failure hospitalization and all-cause mortality | measured by telephone contact | Up to six months | 
| Incidence of Treatment-associated Serious and non-serious adverse events. | Serious and non-serious adverse events (AE) will be registered, which include:start date AE, duration AE, end-date AE, treatment group, continuation of AE after dose interruption, causality with study medication, presence of risk factors for AE and response to AE (sequela or recovery). | During intravenous study drug administration and 1-hour in hospital follow-up |