Clinical trial NCT06434025: IV Iron and SGLT2 Inhibitor on Ventricular Function and Myocardial Iron Content in Heart Failure With Iron Deficiency
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.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Heart Failure, Systolic
Iron Deficiencies
Keywords: heart failure
iron deficiency
SGLT2 inhibitor
intravenous iron
clinical trial
Lead sponsor: Hospital de Clinicas de Porto Alegre
Sponsor class: OTHER
Collaborators: name: Vifor Pharma
First posted: 2024-05-30
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: left ventricular function assessed (LVEF) by CMR.
timeFrame: 30 days
Secondary outcomes:
measure: Myocardial iron content assessed by T2* CMR
timeFrame: 30 days
measure: myocardial strain assessed by T2* CMR
timeFrame: 30 days
Other outcomes:
measure: six minute walk test (6MWT)
timeFrame: 30 days
measure: NT-proBNP
timeFrame: 30 days
measure: MLHFQ
timeFrame: 30 days
measure: Hepcidin
timeFrame: 30 days
measure: Reticulocyte hemoglobin content
timeFrame: 30 days
measure: Transferrin soluble receptors
timeFrame: 30 days
measure: Glomerular filtration rate
timeFrame: 30 days
Locations:
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
state: RS
Study officials:
affiliation: Hospital de Clinicas de Porto Alegre
name: LUIS BECK DA SILVA, MD ScD
role: PRINCIPAL_INVESTIGATOR
References: