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

Heart Failure, Systolic Clinical Trial

— COMBINED-HF  

Official title:

Effect of Combination of Intravenous Iron and SGLT2 Inhibitor on Ventricular Function and Myocardial Iron Content in Patients With Heart Failure and Iron Deficiency.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06434025
• Other study ID #: 78861724.0.0000.5327
• Secondary ID: 2023-0428
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: May 24, 2024
• Est. completion date: November 24, 2026

Study information

• Verified date: May 2024
• Source: Hospital de Clinicas de Porto Alegre
• Contact: LUIS BECK DA SILVA, MD ScD
• Phone: 55 51 997330870
• Email: lbneto[@]hcpa.edu.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 99
• Est. completion date: November 24, 2026
• Est. primary completion date: May 24, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ?ltration 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 de?ciency 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.

Related Conditions & MeSH terms

• Anemia, Iron-Deficiency
• Heart Failure
• Heart Failure, Systolic

Intervention

Drug:
• Iron Carboxymaltose
Iron Carboxymaltose 500 mg. 2 vials administered IV.
• Dapagliflozin 10mg Tab
Dapagliflozin 10mg Tab, PO, onde a day.
• Placebo of Iron Carboxymaltose
Solution Sodium Chloride 0,9% 100 ml, IV, once.
• Placebo of Dapagliflozin
Equal shape and appearance tab as the tab containing Dapagliflozin 10 mg

Locations

Country	Name	City	State
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	RS

Sponsors (2)

Lead Sponsor	Collaborator
Hospital de Clinicas de Porto Alegre	Vifor Pharma

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	six minute walk test (6MWT)	distance walked in six minute walk test	30 days
Other	NT-proBNP	NT-terminal pro-B-type natriuretic peptide (NT-proBNP) levels	30 days
Other	MLHFQ	Quality of life assessed by the Minnesota Living with Heart Failure Questionnaire	30 days
Other	Hepcidin	Serum Hepcidin levels	30 days
Other	Reticulocyte hemoglobin content	Reticulocyte hemoglobin content	30 days
Other	Transferrin soluble receptors	Transferrin soluble receptors	30 days
Other	Glomerular filtration rate	Glomerular filtration rate	30 days
Primary	left ventricular function assessed (LVEF) by CMR.	LVEF assessed by Cardiac Magnetic Resonance	30 days
Secondary	Myocardial iron content assessed by T2* CMR	Myocardial iron content assessed by T2* CMR	30 days
Secondary	myocardial strain assessed by T2* CMR	myocardial strain assessed by T2* CMR	30 days