Changes in Myocardial Iron After Iron Administration

Heart Failure Clinical Trial

Official title:

Changes in Myocardial Iron Content Following Administration of Intravenous Iron (Myocardial-IRON)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03398681
• Other study ID #: MYOCARDIAL-IRON
• Secondary ID: 2016-004194-40
• Status: Completed
• Phase: Phase 4
• Start date: May 1, 2017
• Est. completion date: July 30, 2018

Study information

• Verified date: July 2019
• Source: Fundación para la Investigación del Hospital Clínico de Valencia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: July 30, 2018
• Est. primary completion date: July 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Ferric carboymaltose
Ferric Carboxymaltose solution [Ferinject® (FCM), Vifor Pharma (Glattbrugg, Switzerland)]
• Placebo (Normal saline)
Normal saline (0.9% weight/volume (w/v) NaCl)

Diagnostic Test:
• Cardiac magnetic resonance
Cardiac magnetic resonance including T2* and T1-mapping sequences

Locations

Country	Name	City	State
Spain	Hospital General de Castellón	Castellón De La Plana	Castellón
Spain	Hospital de Manises	Manises	Valencia
Spain	ERESA	Valencia
Spain	Fundación Investigación Hospital Clínico Universitario de Valencia. Instituto de Investigación Sanitaria INCLIVA.	Valencia
Spain	Hospital General de Valencia	Valencia
Spain	Hospital la Fe	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Fundación para la Investigación del Hospital Clínico de Valencia

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in myocardial iron content assessed by CMR T2*		7 and 30 days
Primary	Changes in myocardial iron content assessed by CMR T1-mapping		7 and 30 days
Secondary	Changes in left ventricular systolic function evaluated with cardiac magnetic resonance	Changes in left ventricular systolic function evaluated with cardiac magnetic resonance	7 and 30 days
Secondary	6-minute walking test	Changes in functional capacity assessed by distance walked in 6 minutes (6-minute walking test)	7 and 30 days
Secondary	New York Heart Association (NYHA) class.	Changes in functional capacity assessed by New York Heart Association (NYHA) class.	7 and 30 days
Secondary	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.	7 and 30 days
Secondary	Antigen carbohydrate 125 (CA125)	Laboratory tests, biomarkers: antigen carbohydrate 125 (CA125)	30 days
Secondary	Amino-terminal pro-brain natriuretic peptide (NT-proBNP)	Laboratory tests, biomarkers: amino-terminal pro-brain natriuretic peptide (NT-proBNP)	30 days
Secondary	Galectin-3	Laboratory tests, biomarkers: galectin-3	30 days
Secondary	ST-2	Laboratory tests, biomarkers: ST-2	30 days
Secondary	High-sensitivity troponin (hsTnT)	Laboratory tests, biomarkers: high-sensitivity troponin (hsTnT)	30 days
Secondary	Cystatin C	Laboratory tests, biomarkers: cystatin C	30 days
Secondary	Neutrophil gelatinase-associated lipocalin (NGAL)	Laboratory tests, biomarkers: neutrophil gelatinase-associated lipocalin (NGAL)	30 days
Secondary	Serum creatinine	Laboratory tests: serum creatinine	30 days
Secondary	Urea	Laboratory tests: urea	30 days
Secondary	Estimated glomerular filtration rate (eGFR)	Laboratory tests: estimated glomerular filtration rate (eGFR)	30 days
Secondary	Hemoglobin	Laboratory tests: hemoglobin	30 days
Secondary	Ferritin	Laboratory tests: ferritin	30 days
Secondary	Transferrin saturation (TSAT)	Laboratory tests: transferrin saturation (TSAT)	30 days
Secondary	soluble transferrin receptor (sTfR)	Laboratory tests: soluble transferrin receptor (sTfR)	30 days
Secondary	Hepcidin	Laboratory tests: hepcidin.	30 days
Secondary	Clinical events: all-cause hospitalizations	All-cause hospitalizations	30 days
Secondary	Clinical events: cardiovascular hospitalizations.	Cardiovascular hospitalizations	30 days
Secondary	Clinical events: heart failure hospitalizations.	Heart failure hospitalizations	30 days
Secondary	Clinical events: time to first hospitalization for any reason.	Time to first hospitalization for any reason.	30 days
Secondary	Clinical events: time to first hospitalization for any cardiovascular reason.	Time to first hospitalization for any cardiovascular reason.	30 days
Secondary	Clinical events: time to first hospitalization due to worsening heart failure.	Time to first hospitalization due to worsening heart failure.	30 days