Heart failure with preserved ejection fraction
Conditions
Interventions
Trade Name: Ferric Carboxymaltose (Ferinject®)
Product Name: Ferric carboxymaltose (Ferinject)
Product Code: RVG 33865
Pharmaceutical Form: Concentrate for solution for infusion
Pharmaceutical form of
Sponsors
Amsterdam UMC, location VUmc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis of HFpEF: Signs/and or symptoms of heart failure, NYHA II or higher (and ambulant); AND LVEF = 50% (by any modality); AND evidence of LV diastolic dysfunction: • PCWP at rest = 15mmHg and/or PCWP during passive leg-lifting = 19 mmHg and/or PCWP during exercise = 25mmHg; if no clinical right heart catheterization was performed, diagnose could be made using: • LV diastolic dysfunction grade II or higher on echocardiogram* with a NT-proBNP level >125 pg/mL). OR • H2FpEF score = 6 2. No other significant cardiac (e.g., significant valvular disease) or extra-cardiac condition (e.g., severe COPD) that explains symptoms. 3. Optimal medical treatment (euvolemic, preferable on SGLT2i and mineralocorticoid receptor antagonist) and remaining symptomatic after offering of a cardiac rehabilitation program. 4. Clinically stable (no change in diuretic for >1 month), co-morbidities managed (e.g. hypertension, atrial fibrillation), cardiac rehabilitation program finished (or offered but refused). 5. ID (ferritin 2.8 m/s 2. mitral valve early inflow (E) velocity (=1.9 m/s) 3. Isovolumic relaxation time (IVRT) (=65 ms) 4. Deceleration time of pulmonary venous diastolic velocity (=220 ms) 5. E/mitral flow propagation velocity (Vp) (=1.4) E/e' ratio (=11) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: A potential subject who meets any of the following criteria will be excluded from participation in this study: 1. Unable or unwilling to sign informed consent 2. Contraindication for FCM • Known allergic reaction to FCM • Clinical signs and/or symptoms of an acute infection • Conditions with high risk of an allergic reaction: severe asthma or eczema, systemic lupus erhytematosus, rheumatoid arthritis or concurrent use of significant immunosuppressive therapy (with an exception of patients who previously have received intravenous iron without allergic response). • Pregnancy • Unexplained, bleeding or hemolytic anaemia • Liver dysfunction (defined as AST or ALT > 3x upper limit of normal) 3. History of (previous 2 months) or planned use of intravenous/oral iron, erythropoietin or blood transfusion 4. Indication for iron supplementation* 5. Hypertrophic cardiomyopathy, cardiac amyloidosis or other infiltrative cardiomyopathy, cardiac storage disease, significant congenital and other structural heart disease 6. Acute coronary syndrome, TIA/CVA, PCI/CABG/valve replacement or any major surgery within 3 months prior 7. Current, planned or recent (previous 6 months) dialysis 8. Known HIV, hepatitis infection or active malignancy (with exception of low-risk prostate cancer (biopsy Gleason score of = 6 and clinical stage T1c or T2a) 9. Unable to undergo the complete study protocol (i.e. RHC, 6MWD) 10. Under 18 years of age 11. Subject currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study. *Based on current Dutch general practitioner guideline
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Asses whether, in patients with heart failure with preserved ejection fraction and iron deficiency, ferric carboxymaltose improves left ventricular diastolic function and skeletal muscle function by improving energy metabolism;Secondary Objective: Whether ferric carboxymaltose corrects iron tissue in end-organs (heart and skeletal muscle);Primary end point(s): Exercise PCWP measured by right heart catheterisation (gold standard for evaluation of left ventricular diastology);Timepoint(s) of evaluation of this end point: 4 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Myocardial and calf muscle PCr/ATP-ratio at rest measured by 31P-MRS. 2. PCr/ATP ratio in calf muscle during exercise . And PCr recovery after exercise 3. Change in mitochondrial function 4. Correction of iron storage in plasma (ao ferritin and TSAT) and organs (MRI of heart / skeletal muscle) 5 Safety endpoints (SAE's) 6. Change in symptoms (NYHA, fatigue-score and quality of life questionairres (KCCQ and EQ-5D) 7. Change in exercise tolerance (6 minute walk test; bicycle ergometry) 8. Change in NTproBNP 9. Change in microvascular function (substudy);Timepoint(s) of evaluation of this end point: 4 months | — |
Countries
Netherlands
Contacts
Public Contactdr. M.L. Handoko, cardiologist
Amsterdam UMC, location VUmc
Outcome results
None listed