Patients with heart failure with preserved ejection fraction (HFpEF) and iron deficiency (ID) with and without anaemia
Conditions
Interventions
Trade Name: Ferinject
Product Name: Ferinject
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Ferrum (III)-Ion
CAS Number: 7705-08-0
Concentration unit: mg/ml milligram(s)/m
Sponsors
Charité – Universitätsmedizin Berlin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient is willing to participate and provides written informed consent; 2. Age =18 years; 3. Clinical diagnosis of heart failure with preserved ejection fraction (HFpEF) with LVEF =45% at screening or within 6 months prior to planned randomisation (assessed by echocardiography or MRI); 4. Ambulatory for at least 7 days with NYHA class II or III at time of randomisation (the screening visit can take place at the end of a hospitalisation); 5. Treated with a diuretic; 6. Presence of atrial fibrillation (AF) at screening or randomisation is allowed in 2 out of 4 patients (calculated per centre); 7. At screening or randomisation, presence of one of the following criteria: a) hospitalisation with a diagnosis of HF within 12 months prior to planned randomisation; OR b) raised plasma levels of natriuretic peptides in a patient with sinus rhythm (i.e. in patients without AF: NT-proBNP >300 pg/mL or BNP >100 pg/mL or MR-proANP >120 pmol/L; in patients with AF: NT-proBNP >600 pg/mL or BNP >200 pg/mL or MR-proANP >250 pmol/l) 8. Evidence of diastolic dysfunction at screening or randomisation, defined as: a) E/E’ >13; OR b) LA width =38 mm; OR c) LA length =50 mm; OR d) LA area =20 cm2; OR e) LA volume =55 ml; OR f) left atrial volume index >28 mL/m2; 9. Haemoglobin >9.0 g/dL and =14.0 g/dL (at screening); 10. ID with ferritin =65 years) yes F.1.3.1 Number of subjects for this age range 200
Exclusion criteria
Exclusion criteria: 1. Unable to sign informed consent 2. Any prior echocardiography measurement of LVEF 38°C; 4. SARS-CoV-2 infection 5. Use of IV iron, erythropoietin or blood transfusions within the previous 60 days; 6. Use of concurrent immunosuppressive therapy; 7. History of acquired iron overload or haemochromatosis (or a first relative with haemochromatosis); 8. Known hypersensitivity to FCM or any other IV iron product; 9. Known bleeding or haemolytic anemia; 10. Presence of any condition that precludes exercise testing, such as decompensated HF, significant musculoskeletal disease, unstable angina pectoris, obstructive cardiomyopathy, severe uncorrected valvular disease, or uncontrolled bradyarrhythmias or tachy-arrhythmias; 11. Probable alternative diagnoses that in the opinion of the investigator could account for the patient’s HF symptoms such as severe obesity, primary pulmonary hypertension, or chronic obstructive pulmonary disease (COPD); hence, patients with the following are excluded: a) Severe COPD, i.e. with known FEV1 110/min; 13. Presence of uncontrolled hypertension with blood pressure >160/100 mm Hg; 14. Renal replacement therapy; 15. Concurrent therapy with an erythropoiesis stimulating agent; 16. Known active malignancy; 17. Known HIV or active hepatitis infection; 18. Pregnancy; 19. Patients, who may be dependent on the sponsor, the investigator or the trial sites, have to exclude from the trial; 20. Lack of willingness to storage and disclosure of pseudonymous disease data in the context of the clinical trial; 21. Participation in another clinical trial within previous 30 days and/or anticipated participation in another trial during this study; 22. Inability to fully comprehend and/or perform study procedures in the investigator’s opinion; 23. Persons staying at an institution due to order by a national body or a court of law (in accordance with the German Arzneimittelgesetz §40, Abs. 1, S. 3, Nr. 4);
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary efficacy endpoint: The primary endpoint is the difference in exercise capacity from baseline to visit 5 as assessed by the 6-minute walking test after initiation of therapy (FCM or placebo/saline) in patients with HFpEF and ID ;Secondary Objective: Secondary endpoints: Secondary endpoints include the difference in 6-minute-walking distance (in meters) from baseline to visits 3, 4, 6 and 7 respectively; PGA assessment at visit 3, 4, 5, 6, and 7; change in NYHA functional class from baseline to visit 3, 4, 5, 6, and 7, respectively. Further, improvement of Quality of Life from baseline as well as kidney function and inflammatory parameters will be assessed.Further assessments include differences in plasma levels of blood parameters of kidney function and inflammation, and differences in quality of life from baseline to respective assessment time point as well as the rate of recurrent events of HF hospitalization and death. Tertiary endpoints (efficacy): Tertiary endpoints are resource use and costs associated with the treatment with IV FCM compared to placebo/saline. ;Primary end point(s): Primary efficacy endpoint: The primary endpoint is the difference in exercise capacity from baseline to visit 5 as assessed by the 6-minute walking test after initiation of therapy (FCM or placebo/saline) in patients with HFpEF and ID ;Timepoint(s) of evaluation of this end point: Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints include the difference in 6-minute-walking distance (in meters) from baseline to visits 3, 4, 6 and 7 respectively; Secondary endpoints: Secondary endpoints include the difference in 6-minute-walking distance (in meters) from baseline to visits 3, 4, 6 and 7 respectively; PGA assessment at visit 3, 4, 5, 6, and 7; change in NYHA functional class from baseline to visit 3, 4, 5, 6, and 7, respectively. Further, improvement of Quality of Life from baseline as well as kidney function and inflammatory parameters will be assessed.Further assessments include differences in plasma levels of blood parameters of kidney function and inflammation, and differences in quality of life from baseline to respective assessment time point as well as the rate of recurrent events of HF hospitalization and death. Tertiary endpoints (efficacy): Tertiary endpoints are resource use and costs associated with the treatment with IV FCM compared to placebo/saline. ;Timepoint(s) of evaluation of this end point: - Change in 6min-walking distance to weeks 3, 4, 6 and 7 respectively, adjusted for baseline; - Change in PGA assessment at visit 3, 4, 5, 6, and 7; - Change in NYHA functional class to visit 3, 4, 5, 6, and 7, respectively, adjusted for baseline; | — |
Countries
Germany, United States
Contacts
Public ContactMedizinische Klinik m.S. Kardiologi
Charité – Universitätsmedizin Berlin
Outcome results
None listed