IV Iron and SGLT2 Inhibitor on Ventricular Function and Myocardial Iron Content in Heart Failure With Iron Deficiency

Phase 3

Not yet recruiting

• Conditions: Heart Failure, Systolic; Iron Deficiencies
• Interventions: Drug: Placebo of Iron Carboxymaltose; Drug: Iron Carboxymaltose; Drug: Placebo of Dapagliflozin; Drug: Dapagliflozin 10mg Tab

• Registration Number: NCT06434025
• Lead Sponsor: Hospital de Clinicas de Porto Alegre

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.

Study Timeline

• Status Verified: 2024-05
• Study First Submitted: 2024-05-23
• Study First Submitted QC: 2024-05-23
• Study Start: 2024-05-24
• Study First Posted: 2024-05-30
• Last Update Submitted: 2024-05-30
• Last Update Posted: 2024-06-03
• Primary Completion: 2026-05-24
• Study Completion: 2026-11-24

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 99

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ferric carboxymaltose + placebo of SGLT2 inhibitor	Placebo of Dapagliflozin	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.
Placebo of ferric carboxymaltose and placebo of SGLT2 inhibitor	Placebo of Iron Carboxymaltose	Patients will receive 2 vials of placebo IV, once; and placebo PO, once a day, for 30 days.
Placebo of ferric carboxymaltose and placebo of SGLT2 inhibitor	Placebo of Dapagliflozin	Patients will receive 2 vials of placebo IV, once; and placebo PO, once a day, for 30 days.
ferric carboxymaltose + SGLT2 inhibitor	Dapagliflozin 10mg Tab	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.
ferric carboxymaltose + SGLT2 inhibitor	Iron Carboxymaltose	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.
ferric carboxymaltose + placebo of SGLT2 inhibitor	Iron Carboxymaltose	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.

Primary Outcome Measures

Name	Time	Method
left ventricular function assessed (LVEF) by CMR.	30 days	LVEF assessed by Cardiac Magnetic Resonance

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Hospital de Clínicas de Porto Alegre; 🇧🇷 Porto Alegre, RS, Brazil