Changes in Myocardial Iron After Iron Administration

Fundación para la Investigación del Hospital Clínico de Valencia53 enrolled

Overview

Recent studies have shown that treatment with intravenous iron in patients with iron deficiency (ID) and heart failure with reduced ejection fraction (HFrEF) improves symptomatology, functional capacity, quality of life, and decreases hospitalizations regardless of anemia. In addition, a decrease in myocardial iron content has been observed in patients with chronic HFrEF. This preliminary evidence has led to postulate that myocardial iron deficiency could play a direct role in the pathogenesis and progression of the disease. The investigators hypothesize that the repletion of myocardial iron would explain part of the benefit of this treatment. Thus, the investigators postulate that cardiac magnetic resonance (CMR) (T2\* and T1-mapping sequences) will be sensible enough to detect changes in myocardial iron content as a result of intravenous iron administration, and that such changes will correlate with simultaneous changes in parameters of heart failure severity. In this double-blind 1:1 randomized study controlled by placebo the investigators aim to determine the changes in myocardial iron content after treatment with intravenous ferric carboxymaltose (FCM) by CMR at 7 and 30 days in patients with stable HFrEF and ID.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Heart Failure Iron-deficiency

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients with ambulatory chronic heart failure * Older than 18 years * Patients in NYHA class II-III on optimal background therapy (as determined by the investigator) for at least 4 weeks with no dose changes of HF drugs during the last 2 weeks (with the exception of diuretics) * Elevated natriuretic peptides levels (NT-proBNP \>400 pg/ml) at the screening visit * Left ventricle ejection fraction \<50% documented in the last 12 months * Iron deficiency defined as: serum ferritin level \<100 μg/L or ferritin level 100-299 μg/L when TSAT is less than 20%, and hemoglobin \<15 g/dL (all at screening) * Participant is willing and able to give informed consent for participation in the study Exclusion Criteria: * Known sensitivity to any of the products to be administered per protocol. * History of acquired iron overload. * Severe valve disease, or being scheduled for cardiac surgery within the next 30 days. * Acute myocardial infarction or acute coronary syndrome, transient ischemic attack, or stroke within the last 3 months prior to randomization. * Coronary artery bypass graft, percutaneous intervention (e.g. cardiac, cerebrovascular, and aortic; diagnostic catheters are allowed), or major surgery, including thoracic and cardiac surgery, within the last 3 months prior to randomization. * Ischemic heart disease scheduled for revascularization procedures within the next 30 days. * HF scheduled for cardiac resynchronization therapy within the next 30 days. * Patients with active bleeding in the last 30 days. * Known active infection or active malignancy. * Subject at an immediate need of transfusion or hemoglobin ≥15 g/dL. * Anemia due to reasons other than iron deficiency * Immunosuppressive therapy or renal dialysis * History of erythropoietin, intravenous iron therapy, and blood transfusion in the previous 12 weeks. * Oral iron therapy at doses \>100 mg/day in previous 1 week prior to randomization. * Subjects with an immediate need for transfusion. * Pregnant or breastfeeding women. * Subject of childbearing potential who is not willing to use adequate contraceptive precautions during the study and for up to 5 days after the last scheduled dose of study medication. * Subject currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study, or subject is receiving other investigational agent(s). * Any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.

Outcomes

Primary Outcomes

Changes in myocardial iron content assessed by CMR T2*

Time frame: 7 and 30 days

Changes in myocardial iron content assessed by CMR T1-mapping

Time frame: 7 and 30 days

Secondary Outcomes

Changes in left ventricular systolic function evaluated with cardiac magnetic resonance

Time frame: 7 and 30 days

6-minute walking test

Changes in functional capacity assessed by distance walked in 6 minutes (6-minute walking test)

Time frame: 7 and 30 days

New York Heart Association (NYHA) class.

Changes in functional capacity assessed by New York Heart Association (NYHA) class.

Time frame: 7 and 30 days

The Kansas City quality of life questionnaire (KCCQ)

Quality of life assessed by The Kansas City quality of life questionnaire (KCCQ). KCCQ is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.

Time frame: 7 and 30 days

Antigen carbohydrate 125 (CA125)

Laboratory tests, biomarkers: antigen carbohydrate 125 (CA125)

Time frame: 30 days

Amino-terminal pro-brain natriuretic peptide (NT-proBNP)

Laboratory tests, biomarkers: amino-terminal pro-brain natriuretic peptide (NT-proBNP)

Time frame: 30 days

Galectin-3

Laboratory tests, biomarkers: galectin-3

Time frame: 30 days

ST-2

Laboratory tests, biomarkers: ST-2

Time frame: 30 days

High-sensitivity troponin (hsTnT)

Laboratory tests, biomarkers: high-sensitivity troponin (hsTnT)

Time frame: 30 days

Cystatin C

Laboratory tests, biomarkers: cystatin C

Time frame: 30 days

Neutrophil gelatinase-associated lipocalin (NGAL)

Laboratory tests, biomarkers: neutrophil gelatinase-associated lipocalin (NGAL)

Time frame: 30 days

Serum creatinine

Laboratory tests: serum creatinine

Time frame: 30 days

Urea

Laboratory tests: urea

Time frame: 30 days

Estimated glomerular filtration rate (eGFR)

Laboratory tests: estimated glomerular filtration rate (eGFR)

Time frame: 30 days

Hemoglobin

Laboratory tests: hemoglobin

Time frame: 30 days

Ferritin

Laboratory tests: ferritin

Time frame: 30 days

Transferrin saturation (TSAT)

Laboratory tests: transferrin saturation (TSAT)

Time frame: 30 days

soluble transferrin receptor (sTfR)

Laboratory tests: soluble transferrin receptor (sTfR)

Time frame: 30 days

Hepcidin

Laboratory tests: hepcidin.

Time frame: 30 days

Clinical events: all-cause hospitalizations

All-cause hospitalizations

Time frame: 30 days

Clinical events: cardiovascular hospitalizations.

Cardiovascular hospitalizations

Time frame: 30 days

Clinical events: heart failure hospitalizations.

Heart failure hospitalizations

Time frame: 30 days

Clinical events: time to first hospitalization for any reason.

Time to first hospitalization for any reason.

Time frame: 30 days

Clinical events: time to first hospitalization for any cardiovascular reason.

Time to first hospitalization for any cardiovascular reason.

Time frame: 30 days

Clinical events: time to first hospitalization due to worsening heart failure.

Time to first hospitalization due to worsening heart failure.

Time frame: 30 days

Changes in Myocardial Iron After Iron Administration

Overview

Conditions

Interventions

Eligibility

Locations (6)

Outcomes

Primary Outcomes

Secondary Outcomes