IV Iron and SGLT2 Inhibitor on Ventricular Function and Myocardial Iron Content in Heart Failure With Iron Deficiency (COMBINED-HF)

Hospital de Clinicas de Porto Alegre

Status and phase: Not yet enrolling; Phase 3

Conditions: Iron Deficiencies; Heart Failure, Systolic

Treatments: Drug: Placebo of Dapagliflozin; Drug: Iron Carboxymaltose; Drug: Placebo of Iron Carboxymaltose; Drug: Dapagliflozin 10mg Tab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06434025

78861724.0.0000.5327

2023-0428 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 99 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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99 participants in 3 patient groups, including a placebo group

ferric carboxymaltose + SGLT2 inhibitor

Experimental group

Description:

Patients will receive 2 vials of ferric carboxymaltose 500 mg (Ferinject® 500 mg, Vifor-Pharma) IV, once; and Dapagliflozin 10 mg PO, once a day, for 30 days.

Treatment:

Drug: Dapagliflozin 10mg Tab

Drug: Iron Carboxymaltose

ferric carboxymaltose + placebo of SGLT2 inhibitor

Active Comparator group

Description:

Patients will receive 2 vials of ferric carboxymaltose 500 mg (Ferinject® 500 mg, Vifor-Pharma) IV, once; and placebo PO, once a day, for 30 days.

Treatment:

Drug: Iron Carboxymaltose

Drug: Placebo of Dapagliflozin

Placebo of ferric carboxymaltose and placebo of SGLT2 inhibitor

Placebo Comparator group

Description:

Patients will receive 2 vials of placebo IV, once; and placebo PO, once a day, for 30 days.

Treatment:

Drug: Placebo of Iron Carboxymaltose

Drug: Placebo of Dapagliflozin