Ferric derisomaltose for Heart failure | Iron deficiency | Mild cognitive impairment

Inclusion criteria

• {"criterion_text":"- The Patient is willing and able to participate and provides written informed consent\n- 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\n- Screening ferritin < 100 ng/ml or ferritin 100-299 ng/ml if TSAT < 20 %\n- Hb: ≥10 < 15.0 g/dl\n- Patient must be able to perform the 6-minute walking test und handgrip strength measurements according to investigator judgment\n- 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\n- Age ≥ 18 years and < 85\n- NYHA II-III functional class due to stable symptomatic chronic HF and all of the following\n- Three months without cardiac hospitalization\n- 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\n- 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\n- No dose changes of HF drugs during the last 2 weeks (exception for diuretics)\n- No introduction of a new HF drug class during the last 4 weeks\n- LVEF ≤ 40 % for both groups of NYHA functional classes; documented within the last 12 months prior to screening"}

Exclusion criteria

• {"criterion_text":"- Clinical signs and symptoms of infection or C-reactive protein > 20 mg/l\n- Renal replacement therapy (previous, current or planned within the next 6 months) or haemodialysis\n- Severe valvular or left ventricular outflow obstruction disease, obstructive cardiomyopathy\n- Atrial fibrillation/flutter with a mean ventricular response rate in rest > 100 bpm\n- Uncontrolled hypertension with blood pressure > 160/100 mmHg\n- Acute coronary syndrome (STEMI, NSTEMI or unstable angina pectoris), transient ischaemic attack or stroke within the last 3 months\n- 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\n- Implantation of CRT/ICD within the past 3 months or planned during the study\n- Subject is pregnant (e.g., positive ß-hCG test) or is breast feeding\n- Women of childbearing potential (WOCBP) and not using highly effective contraception refer to CTFG\n- History of acquired iron overload or hemochromatosis (or a first relative with hemochromatosis)\n- Clinically significant bleeding and subject at an immediate need of transfusion\n- Hypersensitivity to the active substance, to FDI or any of its excipients\n- Earlier hypersensitivity to parental iron preparations or a history of allergic disorders\n- History of severe asthma, eczema or other atopic allergy\n- History of immune or inflammatory conditions (e.g. systemic lupus erythematosus, rheumatoid arthritis)\n- Concurrent immunosuppressive therapy\n- Diagnosis of Psychosis or dementia\n- MoCa < 19\n- Prescribed anti-dementia medication\n- Known history of alcohol or drug abuse within 5 years prior\n- 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.\n- Active malignancy with exception of basal cell or squamous cell carcinoma of the skin, and cervical intraepithelial neoplasia\n- Diagnosed current severe depressive episode (according to ICD-10-GM)\n- History of erythropoetin, IV or oral iron therapy, and blood transfusion in previous 4 weeks\n- Chronic liver disease and/or screening alanine transaminase (ALAT) or aspartate transaminase (ASAT) above three times the upper limit of the normal range\n- Vitamin B12 and/or serum folate deficiency. If deficiency is corrected, patients may be re-screened for inclusion\n- Haemolytic anaemia and other forms of anaemia not based on ID (e.g. other microcytic anaemia, pernicious anaemia)\n- Medical treatment for known HIV/AIDS\n- Currently receiving systemic chemotherapy and/or radiotherapy"}

Primary endpoints

• {"endpoint_text":"- Changes in cognitive performance at week 12, compared to baseline, as assessed by a global composite score of cognitive function. This score constitutes the average of z-standardized results of the Digit Symbol Substitution Test, Stroop Color Word Interference Task, Trailmaking-Test, CERAD-Wordlist, Digit Span Backwards Test, and Digit Span Forwards Test.","definition_or_measurement_approach":"Global composite score: the average of z-standardized results of the Digit Symbol Substitution Test, Stroop Color Word Interference Task, Trailmaking-Test, CERAD-Wordlist, Digit Span Backwards Test, and Digit Span Forwards Test; change at week 12 vs baseline."}

Secondary endpoints

• {"endpoint_text":"- Changes in cognitive performance at week 24, compared to baseline, as assessed by the global composite score of cognitive function (single items for composite score see 3.2.1 Primary Endpoint).","definition_or_measurement_approach":"Global composite score as defined for the primary endpoint; change at week 24 vs baseline."}
• {"endpoint_text":"- Changes in single measures and domain specific subscores (e.g. frontal executive function, perceptual speed, memory subsystems) of cognitive performance at week 12 and 24 compared to baseline, as assessed by the MoCA Test, Digit Symbol Substitution Test, Stroop Color Word Interference Task, Trailmaking-Test, CERAD- Wordlist, Digit Span Backwards Test, and Digit Span Forwards Test.","definition_or_measurement_approach":"Assessment via individual cognitive tests and calculation of domain-specific subscores at weeks 12 and 24 vs baseline."}
• {"endpoint_text":"- Reduction in depression from baseline to week 12 and 24, as assessed by HADS","definition_or_measurement_approach":"Depression measured using HADS (Hospital Anxiety and Depression Scale); change at weeks 12 and 24 vs baseline."}
• {"endpoint_text":"- Reduction in general anxiety and heart-focused anxiety from baseline to week 12 and 24, as assessed by HADS and HAF-17.","definition_or_measurement_approach":"Anxiety assessed by HADS and heart-focused anxiety by HAF-17; changes at weeks 12 and 24 vs baseline."}
• {"endpoint_text":"- Changes in self-reported quality of life, as assessed by The Kansas City Cardiomyopathy Questionnaire (for HF specific quality of life) and EQ-5D (for general psychological and physical quality of life) from baseline to week 12 and 24.","definition_or_measurement_approach":"Quality of life measured by KCCQ and EQ-5D; change from baseline to weeks 12 and 24."}

Germany

Earliest CTIS Part Ii Submission Date

12-08-2024

Latest Decision Or Authorization Date

20-08-2024

Processing Time Days

8

Number Of Sites

2

Number Of Participants

40

Primary sponsor

Full Name

Universitaetsmedizin Goettingen

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany