Cognitive Function, Depression, Anxiety, and Quality of Life in Chronic Heart Failure Patients with Iron Deficiency with and without Anaemia: Effects of Intravenous Iron (Ferric Derisomaltose) CogFer-HF Study

Prior treatment

• Renal replacement therapy (previous, current or planned within the next 6 months) or haemodialysis
• Concurrent immunosuppressive therapy
• Known history of alcohol or drug abuse within 5 years prior
• Medications that may negatively affect cognitive function (eg, sedatives, antipsychotics, anti-epileptics) are not allowed unless subjects are on a stable dose at the time of screening and are expected to continue on a stable dose for the duration of the trial.
• History of erythropoetin, IV or oral iron therapy, and blood transfusion in previous 4 weeks
• Currently receiving systemic chemotherapy and/or radiotherapy

Other illness

• Clinical signs and symptoms of infection or C-reactive protein > 20 mg/l
• Severe valvular or left ventricular outflow obstruction disease, obstructive cardiomyopathy
• Uncontrolled hypertension with blood pressure > 160/100 mmHg
• Acute coronary syndrome (STEMI, NSTEMI or unstable angina pectoris), transient ischaemic attack or stroke within the last 3 months
• Coronary-artery bypass graft, percutaneous intervention (cardiac, cerebrovascular, aortic; diagnostic catheters are allowed) or major surgery, including thoracic and cardiac surgery, within the last 3 months or planned during the study
• History of acquired iron overload or hemochromatosis (or a first relative with hemochromatosis)
• Clinically significant bleeding and subject at an immediate need of transfusion
• Hypersensitivity to the active substance, to FDI or any of its excipients
• Earlier hypersensitivity to parental iron preparations or a history of allergic disorders
• History of severe asthma, eczema or other atopic allergy
• History of immune or inflammatory conditions (e.g. systemic lupus erythematosus, rheumatoid arthritis)
• Diagnosis of Psychosis or dementia
• Prescribed anti-dementia medication
• Active malignancy with exception of basal cell or squamous cell carcinoma of the skin, and cervical intraepithelial neoplasia
• Medical treatment for known HIV/AIDS

Lab values

• Chronic liver disease and/or screening alanine transaminase (ALAT) or aspartate transaminase (ASAT) above three times the upper limit of the normal range
• Vitamin B12 and/or serum folate deficiency. If deficiency is corrected, patients may be re-screened for inclusion

Other

• Atrial fibrillation/flutter with a mean ventricular response rate in rest > 100 bpm
• Implantation of CRT/ICD within the past 3 months or planned during the study
• Subject is pregnant (e.g., positive ß-hCG test) or is breast feeding
• Women of childbearing potential (WOCBP) and not using highly effective contraception refer to CTFG
• MoCa < 19
• Diagnosed current severe depressive episode (according to ICD-10-GM)
• Haemolytic anaemia and other forms of anaemia not based on ID (e.g. other microcytic anaemia, pernicious anaemia)

• The Patient is willing and able to participate and provides written informed consent
• At screening or Visit 1, significantly raised plasma levels of natriuretic peptides (NT-proBNP ≥ 600 pg/ml or BNP ≥ 150 pg/ml) or if they have been hospitalized for HF within the previous 12 months, a NT-proBNP ≥ 400 pg/ml or BNP of at least 100 pg/ml or by patients with atrial fibrillation and HF, a NT-proBNP ≥ 900 pg/ml
• Screening ferritin < 100 ng/ml or ferritin 100-299 ng/ml if TSAT < 20 %
• Hb: ≥10 < 15.0 g/dl
• Patient must be able to perform the 6-minute walking test und handgrip strength measurements according to investigator judgment
• Mild cognitive impairment according to MoCA Test (MoCa Score of 19- 25, including), subjective memory concern reported by patient, informant or clinician, preserved activities of daily living
• Age ≥ 18 years and < 85
• NYHA II-III functional class due to stable symptomatic chronic HF and all of the following
• Three months without cardiac hospitalization
• Patients in NYHA II: Acute care admission or emergency room visit for worsening HF at least once within 24 months prior to start of treatment, but not in the last three months
• Appropriate dose of medical therapy for HF (such as ACEi, ARB, ß- blocker, oral diuretics, MRA, ARNI, ivabradine) consistent with prevailing local and international CV guidelines
• No dose changes of HF drugs during the last 2 weeks (exception for diuretics)
• No introduction of a new HF drug class during the last 4 weeks
• LVEF ≤ 40 % for both groups of NYHA functional classes; documented within the last 12 months prior to screening