NCT03398681

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
53

participants targeted

Target at P25-P50 for phase_4 heart-failure

Timeline
Completed

Started May 2017

Shorter than P25 for phase_4 heart-failure

Geographic Reach
1 country

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2017

Completed
7 months until next milestone

First Submitted

Initial submission to the registry

November 21, 2017

Completed
2 months until next milestone

First Posted

Study publicly available on registry

January 12, 2018

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 30, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 30, 2018

Completed
Last Updated

July 30, 2019

Status Verified

July 1, 2019

Enrollment Period

1.2 years

First QC Date

November 21, 2017

Last Update Submit

July 29, 2019

Conditions

Heart FailureIron-deficiency

Keywords

Heart failureIron deficiencyCardiac magnetic resonanceFerric carboxymaltoseMyocardial iron

Outcome Measures

Primary Outcomes (2)

  • Changes in myocardial iron content assessed by CMR T2*

    7 and 30 days

  • Changes in myocardial iron content assessed by CMR T1-mapping

    7 and 30 days

Secondary Outcomes (25)

  • Changes in left ventricular systolic function evaluated with cardiac magnetic resonance

    7 and 30 days

  • 6-minute walking test

    7 and 30 days

  • New York Heart Association (NYHA) class.

    7 and 30 days

  • The Kansas City quality of life questionnaire (KCCQ)

    7 and 30 days

  • Antigen carbohydrate 125 (CA125)

    30 days

  • +20 more secondary outcomes

Study Arms (2)

Intravenous ferric carboxymaltose

ACTIVE COMPARATOR

Ferric Carboxymaltose solution \[Ferinject® (FCM), Vifor Pharma (Glattbrugg, Switzerland)\] will be given as a perfusion of 20 mL (which is the amount of FCM that is equivalent to 1000 mg of iron) diluted in a sterile saline solution (0.9% weight/volume (w/v) NaCl) administered over at least 15 min.

Drug: Ferric carboymaltoseDiagnostic Test: Cardiac magnetic resonance

Normal saline

PLACEBO COMPARATOR

Normal saline (0.9% weight/volume (w/v) NaCl) administered as per the instructions for active therapy.

Drug: Placebo (Normal saline)Diagnostic Test: Cardiac magnetic resonance

Interventions

Ferric carboymaltoseDRUG

Ferric Carboxymaltose solution \[Ferinject® (FCM), Vifor Pharma (Glattbrugg, Switzerland)\]

Also known as: Ferinject, intravenous iron
Intravenous ferric carboxymaltose
Placebo (Normal saline)DRUG

Normal saline (0.9% weight/volume (w/v) NaCl)

Normal saline
Cardiac magnetic resonanceDIAGNOSTIC_TEST

Cardiac magnetic resonance including T2\* and T1-mapping sequences

Intravenous ferric carboxymaltoseNormal saline

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Hospital General de Castellón

Castellon, Castellón, Spain

Location

Hospital de Manises

Manises, Valencia, Spain

Location

ERESA

Valencia, 46010, Spain

Location

Fundación Investigación Hospital Clínico Universitario de Valencia. Instituto de Investigación Sanitaria INCLIVA.

Valencia, 46010, Spain

Location

Hospital General de Valencia

Valencia, Spain

Location

Hospital la Fe

Valencia, Spain

Location

Related Publications (4)

  • Del Canto I, Santas E, Cardells I, Minana G, Palau P, Llacer P, Facila L, Lopez-Vilella R, Almenar L, Bodi V, Lopez-Lereu MP, Monmeneu JV, Sanchis J, Moratal D, Maceira AM, de la Espriella R, Chorro FJ, Bayes-Genis A, Nunez J; Myocardial-IRON Investigators dagger. Short-Term Changes in Left and Right Ventricular Cardiac Magnetic Resonance Feature Tracking Strain Following Ferric Carboxymaltose in Patients With Heart Failure: A Substudy of the Myocardial-IRON Trial. J Am Heart Assoc. 2022 Apr 5;11(7):e022214. doi: 10.1161/JAHA.121.022214. Epub 2022 Mar 18.

    PMID: 35301854DERIVED

  • Meucci MC, Reinders MEJ, Groeneweg KE, Bezstarosti S, Ajmone Marsan N, Bax JJ, De Fijter JW, Delgado V. Cardiovascular Effects of Autologous Bone Marrow-Derived Mesenchymal Stromal Cell Therapy With Early Tacrolimus Withdrawal in Renal Transplant Recipients: An Analysis of the Randomized TRITON Study. J Am Heart Assoc. 2021 Dec 21;10(24):e023300. doi: 10.1161/JAHA.121.023300. Epub 2021 Dec 16.

    PMID: 34913362DERIVED

  • Nunez J, Minana G, Cardells I, Palau P, Llacer P, Facila L, Almenar L, Lopez-Lereu MP, Monmeneu JV, Amiguet M, Gonzalez J, Serrano A, Montagud V, Lopez-Vilella R, Valero E, Garcia-Blas S, Bodi V, de la Espriella-Juan R, Lupon J, Navarro J, Gorriz JL, Sanchis J, Chorro FJ, Comin-Colet J, Bayes-Genis A; Myocardial-IRON Investigators* dagger. Noninvasive Imaging Estimation of Myocardial Iron Repletion Following Administration of Intravenous Iron: The Myocardial-IRON Trial. J Am Heart Assoc. 2020 Feb 18;9(4):e014254. doi: 10.1161/JAHA.119.014254. Epub 2020 Feb 13.

    PMID: 32067585DERIVED

  • Minana G, Cardells I, Palau P, Llacer P, Facila L, Almenar L, Lopez-Lereu MP, Monmeneu JV, Amiguet M, Gonzalez J, Serrano A, Montagud V, Lopez-Vilella R, Valero E, Garcia-Blas S, Bodi V, de la Espriella-Juan R, Sanchis J, Chorro FJ, Bayes-Genis A, Nunez J; Myocardial-IRON Investigators. Changes in myocardial iron content following administration of intravenous iron (Myocardial-IRON): Study design. Clin Cardiol. 2018 Jun;41(6):729-735. doi: 10.1002/clc.22956. Epub 2018 Jun 5.

    PMID: 29607528DERIVED

MeSH Terms

Conditions

Heart FailureAnemia, Iron-DeficiencyIron Deficiencies

Interventions

ferric carboxymaltoseSaline Solution

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular DiseasesAnemia, HypochromicAnemiaHematologic DiseasesHemic and Lymphatic DiseasesIron Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Crystalloid SolutionsIsotonic SolutionsSolutionsPharmaceutical Preparations

Study Officials

  • Julio Nuñez, MD PhD

    Fundación Investigación Hospital Clínico Universitario de Valencia. Instituto de Investigación Sanitaria INCLIVA.

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Masking Details
Because ferric carboxymaltose is a dark-brown solution that is easily distinguishable from the saline placebo, study personnel responsible for the preparation and administration of the study drug will aware of the group assignments and therefore, not involved in any study assessments. To ensure that patients will be unaware of the study drug, materials used in drug administration will be covered with aluminum foil or other opaque material and the injection site shield from the patient view. Once treatment is allocated, the investigators team will ensure that patients are blinded to the treatment received.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: After providing informed consent, patients will be randomly assigned, with a remote, web-based computer-generated block randomization procedure in an allocation 1:1 ratio, to either receive intravenous ferric carboxymaltose (FCM) or placebo. Intramyocardial iron will be evaluated at 3 time points: before administration of CMF/placebo, and at 7 and 30 days. At 30 days, patients assigned to placebo will receive intravenous CMF if iron deficiency persists.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal investigator

Study Record Dates

First Submitted

November 21, 2017

First Posted

January 12, 2018

Study Start

May 1, 2017

Primary Completion

July 30, 2018

Study Completion

July 30, 2018

Last Updated

July 30, 2019

Record last verified: 2019-07

Locations

ES(6)