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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsmedizin Goettingen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Decision date (initial)

2024-08-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515046-17-00

EudraCT number

2021-005383-22

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective of the study is to evaluate the effect of iron repletion with intravenous Ferric Derisomaltose (IV FDI) after 12 weeks on cognitive function as assessed using a composite score of cognitive function, in patients with stable chronic HF (NYHA class II-III, LVEF ≤ 40 %) and ID.

Secondary objectives 1

1. Secondary objectives are changes in cognitive performance at week 24, changes in single cognitive measures and domain specific subscores, reduction in depression, general anxiety and heart-focused anxiety, changes in self-reported quality of life

Conditions and MedDRA coding

Heart Failure

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. The Patient is willing and able to participate and provides written informed consent
2. Age ≥ 18 years and < 85
3. NYHA II-III functional class due to stable symptomatic chronic HF and all of the following
4. Three months without cardiac hospitalization
5. 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
6. 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
7. No dose changes of HF drugs during the last 2 weeks (exception for diuretics)
8. No introduction of a new HF drug class during the last 4 weeks
9. LVEF ≤ 40 % for both groups of NYHA functional classes; documented within the last 12 months prior to screening
10. 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
11. Screening ferritin < 100 ng/ml or ferritin 100-299 ng/ml if TSAT < 20 %
12. Hb: ≥10 < 15.0 g/dl
13. Patient must be able to perform the 6-minute walking test und handgrip strength measurements according to investigator judgment
14. 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

Exclusion criteria 30

1. Clinical signs and symptoms of infection or C-reactive protein > 20 mg/l
2. Clinically significant bleeding and subject at an immediate need of transfusion
3. Active malignancy with exception of basal cell or squamous cell carcinoma of the skin, and cervical intraepithelial neoplasia
4. History of erythropoetin, IV or oral iron therapy, and blood transfusion in previous 4 weeks
5. Chronic liver disease and/or screening alanine transaminase (ALAT) or aspartate transaminase (ASAT) above three times the upper limit of the normal range
6. Vitamin B12 and/or serum folate deficiency. If deficiency is corrected, patients may be re-screened for inclusion
7. Haemolytic anaemia and other forms of anaemia not based on ID (e.g. other microcytic anaemia, pernicious anaemia)
8. Medical treatment for known HIV/AIDS
9. Currently receiving systemic chemotherapy and/or radiotherapy
10. Renal replacement therapy (previous, current or planned within the next 6 months) or haemodialysis
11. Severe valvular or left ventricular outflow obstruction disease, obstructive cardiomyopathy
12. Atrial fibrillation/flutter with a mean ventricular response rate in rest > 100 bpm
13. Uncontrolled hypertension with blood pressure > 160/100 mmHg
14. Acute coronary syndrome (STEMI, NSTEMI or unstable angina pectoris), transient ischaemic attack or stroke within the last 3 months
15. 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
16. Implantation of CRT/ICD within the past 3 months or planned during the study
17. Subject is pregnant (e.g., positive ß-hCG test) or is breast feeding
18. Women of childbearing potential (WOCBP) and not using highly effective contraception refer to CTFG
19. History of acquired iron overload or hemochromatosis (or a first relative with hemochromatosis)
20. Hypersensitivity to the active substance, to FDI or any of its excipients
21. Earlier hypersensitivity to parental iron preparations or a history of allergic disorders
22. History of severe asthma, eczema or other atopic allergy
23. History of immune or inflammatory conditions (e.g. systemic lupus erythematosus, rheumatoid arthritis)
24. Concurrent immunosuppressive therapy
25. Diagnosis of Psychosis or dementia
26. MoCa < 19
27. Prescribed anti-dementia medication
28. Known history of alcohol or drug abuse within 5 years prior
29. 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.
30. Diagnosed current severe depressive episode (according to ICD-10-GM)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 5

1. 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).
2. 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.
3. Reduction in depression from baseline to week 12 and 24, as assessed by HADS
4. Reduction in general anxiety and heart-focused anxiety from baseline to week 12 and 24, as assessed by HADS and HAF-17.
5. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsmedizin Goettingen

Sponsor organisation

Universitaetsmedizin Goettingen

Address

Robert-Koch-Strasse 40, Weende Weende

City

Goettingen

Postcode

37075

Country

Germany

Scientific contact point

Organisation

Universitaetsmedizin Goettingen

Contact name

Annika Wille

Public contact point

Organisation

Universitaetsmedizin Goettingen

Contact name

Annika Wille

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications