Heart Failure, Systolic, Iron Deficiencies
Conditions
Keywords
heart failure, iron deficiency, SGLT2 inhibitor, intravenous iron, clinical trial
Brief summary
Background. Treatment with intravenous iron has been shown to improve symptoms, functional capacity, and quality of life in patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency. However, the mechanisms underlying these beneficial effects remain unknown. SGLT2i seem to alter hematocrit and other hematological markers or iron content. This study aims to measure cardiac magnetic resonance changes in myocardial iron content and in left ventricular function after administration of intravenous iron with and without the concomitant use of SGLT2 inhibitor in patients with HFrEF and iron deficiency.
Detailed description
Background. Treatment with intravenous iron has been shown to improve symptoms, functional capacity, and quality of life in patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency. However, the mechanisms underlying these beneficial effects remain unknown. SGLT2i seem to alter hematocrit and other hematological markers or iron content. This study aims to measure cardiac magnetic resonance changes in myocardial iron content after administration of intravenous iron and to assess changes in left ventricular function in patients with HFrEF and iron deficiency. Methods. Ninety-nine outpatient with symptomatic HFrEF, left ventricular ejection fraction (LVEF) \<40%, SGLT2i naive, and iron deficiency will be assigned, to receive intravenous iron + SGLT2i; or intravenous iron + placebo of SGLT2i; or placebo of both therapies for 30 days. Myocardial iron will be evaluated by T2-star (T2\*) cardiac magnetic resonance (CMR) sequencing before intravenous iron infusion. After 30 days, all patients will be reassessed by T2\* CMR sequencing. The primary endpoint will be changes in LVEF and myocardial iron content at 30 days. Secondary endpoints will include correlations of these changes with myocardial iron content, functional capacity, quality of life, and cardiac biomarkers. Conclusions. This study will determine the effect of ferric carboxymaltose and its combination with SGLT2i on LVEF and its relationship with measures of myocardial iron content, functional capacity, and biomarkers in HFrEF and iron deficiency.
Interventions
Iron Carboxymaltose 500 mg. 2 vials administered IV.
DRUGDapagliflozin 10mg Tab
Dapagliflozin 10mg Tab, PO, onde a day.
DRUGPlacebo of Iron Carboxymaltose
Solution Sodium Chloride 0,9% 100 ml, IV, once.
DRUGPlacebo of Dapagliflozin
Equal shape and appearance tab as the tab containing Dapagliflozin 10 mg
Sponsors
Vifor Pharma
Hospital de Clinicas de Porto Alegre
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Caregiver, Investigator, Outcomes Assessor)
Intervention model description
HFrEF, LVEF \<40%, SGLT2i naive, and iron deficiency. Assigned to receive: 1. intravenous iron + SGLT2i; 2. intravenous iron + placebo of SGLT2i; 3. placebo of both therapies.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 18 years or over; 2. Ejection fraction (EF) ≤40%, estimated by color Doppler echocardiography or CMR or radionuclide ventriculography; 3. Serum ferritin \<100 µg/L or serum ferritin between 100 and 299 µg/L and transferrin saturation \<20%; 4. Serum hemoglobin between 9.5 and 13.5 mg/dL; 5. Patients must be SGLT2 naive; 6. Informed consent form (ICF) signed.
Exclusion criteria
1. Kidney disease requiring dialysis or chronic kidney disease not requiring dialysis with an estimated glomerular filtration rate \<30 mL/min/1.73 m2 calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation; 2. Severe primary valve disease; 3. Acute coronary syndrome requiring cardiac surgery or coronary artery bypass surgery in the past 3 months; 4. Patients already being treated for some type of non-iron deficiency anemia; 5. Blood transfusion within 30 days prior to CMR examination; 6. Patients with a pacemaker, cardiac resynchronization therapy, or implantable defibrillator; 7. Diagnosis of hemochromatosis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| left ventricular function assessed (LVEF) by CMR. | 30 days | LVEF assessed by Cardiac Magnetic Resonance |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| myocardial strain assessed by T2* CMR | 30 days | myocardial strain assessed by T2\* CMR |
| Myocardial iron content assessed by T2* CMR | 30 days | Myocardial iron content assessed by T2\* CMR |
Other
| Measure | Time frame | Description |
|---|---|---|
| Hepcidin | 30 days | Serum Hepcidin levels |
| Reticulocyte hemoglobin content | 30 days | Reticulocyte hemoglobin content |
| six minute walk test (6MWT) | 30 days | distance walked in six minute walk test |
| Glomerular filtration rate | 30 days | Glomerular filtration rate |
| Transferrin soluble receptors | 30 days | Transferrin soluble receptors |
| NT-proBNP | 30 days | NT-terminal pro-B-type natriuretic peptide (NT-proBNP) levels |
| MLHFQ | 30 days | Quality of life assessed by the Minnesota Living with Heart Failure Questionnaire |
Countries
Brazil
Contacts
Primary ContactLUIS BECK DA SILVA, MD ScD
Outcome results
None listed