E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Heart failure with reduced left ventricular ejection fraction |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019279 |
E.1.2 | Term | Heart failure |
E.1.2 | System Organ Class | 100000004849 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
To assess left ventricular reverse remodeling also defined as left ventricular volumes and cardiac biomarkers |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients with 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 < 45%). 2. Age ≥18 years 3. Obtained informed consent 4. Stable pharmacological therapy of heart failure during the last 4 weeks (with the exception of diuretics) |
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E.4 | Principal exclusion criteria |
1. Hemochromatosis, iron overload, defined as TSAT > 45% 2. Hemoglobin > 15 g/dl at inclusion 3. Known hypersensitivity to injectafer®. 4. Known active infection, CRP>20 mg/L, clinically significant bleeding, active malignancy. 5. Chronic liver disease and/or screening alanine transaminase (ALT) or aspartate transaminase (AST) above three times the upper limit of the normal range. 6. Immunosuppressive therapy or renal dialysis (current or planned within the next 6 months). 7. 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. 8. 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. 9. Acute myocardial infarction or acute coronary syndrome, transient ischemic attack or stroke within the last 3 months. 10. 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. 11. Inability to fully comprehend and/or perform study procedures in the investigator's opinion. 12. Vitamin B12 and/or serum folate deficiency according to the laboratory (re-screening is possible after substitution therapy). 13. Pregnancy or lactation. 14. Participation in another clinical trial within previous 30 days and/or anticipated participation in another trial during this study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in left ventricular ejection fraction |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Change in left ventricular end-diastolic, end-systolic volume and cardiac biomarkers |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |