Ferric Carboxymaltose to Improve Skeletal Muscle Metabolism in Heart Failure Patients With Functional Iron Deficiency

The purpose of this study is to better understand how body levels of iron affect the ability to exercise in patients with heart failure (HF).

Heart failure is a condition in which abnormal pumping action of the heart reduces the flow of blood to the body. Patients with heart failure may feel shortness of breath or leg fatigue when they exercise. Iron is an essential nutrient in the diet. In heart failure patients, low body levels of iron might increase shortness of breath and fatigue.

Study Overview

• Status: Terminated
• Conditions: Iron-deficiency
• Intervention / Treatment: Drug: Ferric Carboxymaltose; Device: 31P MRS/MRI; Drug: Placebo

Detailed Description

The purpose of this prospective, double blind parallel group randomized study is to compare the effects of ferric carboxymaltose vs. placebo on skeletal muscle mitochondrial oxidative capacity, submaximal exercise tolerance, and health-related quality of life in non-anemic Heart Failure (HF) patients with functional iron deficiency.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • New York University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Symptomatic NYHA Class II-III heart failure >3 months
• Guideline-recommended heart failure treatment for > 3 months
• Hemoglobin >13 g/dl for men and >12 g/dl for women
• Functional iron deficiency (defined as serum ferritin level <100 ng/ml or between 100 and 299 ng/ml with transferrin saturation <20%)
• Left ventricular ejection fraction <40%, or left ventricular ejection fraction ≥40% with left atrial enlargement (left atrial volume index >28 ml/m2) and/or left ventricular hypertrophy (left ventricular mass index >95 g/m2 (women) or >115 g/m2 (men) determined by echocardiogram within last 24 months.
• Able and willing to provide written informed consent

Exclusion Criteria:

• Presence of implantable defibrillator, permanent pacemaker, other metal implant not compatible with 3TMRS/MRI, or other contraindication to 3T MRS/MRI procedures
• Heart failure due to infiltrative cardiomyopathy, restrictive cardiomyopathy, or hypertrophic cardiomyopathy
• Weight <50 kg or >120 kg
• Coronary or cerebral atherothrombotic events in the past 6 months
• Hospitalization of emergency room visit for heart failure within past 3 months
• ICD shock in last 3 months
• Known peripheral artery disease or ankle-brachial index <0.9 at screening visit
• Exercise primarily limited by angina, lung disease or neuromuscular disease
• Systolic blood pressure <100 or >160 mmHg
• Heart rate <50 or >110 min-1
• Estimated glomerular filtration rate <30 ml/min
• Liver function tests >3 times upper limit of normal
• Serum phosphate below normal limit
• Pregnant or breast-feeding women
• Women of child-bearing potential unwilling to use recommended contraception methods during the study
• Treatment with oral iron supplements (except multivitamins) in past year
• Treatment with intravenous iron in past year
• Treatment with erythropoiesis stimulating agents in the past year
• Known intolerance of intravenous iron
• History of anaphylaxis
• Participation in another clinical trial within last 30 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ferric Carboxymaltose; HF patients with functional iron deficiency assigned to receive one-time dose of Ferric Carboxymaltose 750 mg. Participants will undergo serial assessment before and 4 weeks after study drug administration	Drug: Ferric Carboxymaltose; Intravenous Ferric Carboxymaltose 750 mg mixed under sterile conditions in 100 ml of normal saline for final concentration of 7.5 mg/ml and administered via volumetric infusion pump over 15 minutes.; Other Names: Injectafer; Device: 31P MRS/MRI; Each participant will perform the same rhythmic plantar extension exercise protocol twice, for sequential acquisition of magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) measurements. For the exercise protocol, the participant will lay supine on the scanning table with the right leg inside the volume coil. The exercise consists of repeated plantar flexion movements using resistance bands at a frequency of one repetition per second for 1-2 minutes. Data are collected continuously for 2 minutes before the exercise (baseline), during exercise, and 5 minutes after the exercise for the MRS and MRI experiments.; Other Names: 3T Siemens MRI
Active Comparator: Placebo; HF patients with functional iron deficiency assigned to receive one-time dose of Placebo (saline injection). Participants will undergo serial assessment before and 4 weeks after study drug administration.	Device: 31P MRS/MRI; Each participant will perform the same rhythmic plantar extension exercise protocol twice, for sequential acquisition of magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) measurements. For the exercise protocol, the participant will lay supine on the scanning table with the right leg inside the volume coil. The exercise consists of repeated plantar flexion movements using resistance bands at a frequency of one repetition per second for 1-2 minutes. Data are collected continuously for 2 minutes before the exercise (baseline), during exercise, and 5 minutes after the exercise for the MRS and MRI experiments.; Other Names: 3T Siemens MRI; Drug: Placebo; 100 ml of normal saline solution, and administered via volumetric infusion pump over 15 minutes.; Other Names: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Post-Exercise Phosphocreatine Recovery Time	Post-exercise phosphocreatine recovery time (in seconds) will be used to assess mitochondrial oxidative capacity. It is measured non-invasively with 31P-magnetic resonance spectroscopy.	Baseline, Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 6-Minute Walk Test Distance	The 6-minute walk test measures the distance that a patient can walk on a flat, hard surface in a period of 6 minutes.	Baseline, Week 4
Change From Baseline in Kansas City Cardiomyopathy Questionnaire Score	23-item self-assessment of symptoms, physical and social limitations, and quality of life in patients with heart failure. KCCQ responses are provided along a rating scale continuum with equal spacing from worst to best. The total score ranges from 0-100, with higher scores indicating better health status. An increase in scores indicates health status improved during the observational period.	Baseline, Week 4
Change From Baseline in Hemoglobin Levels	Hemoglobin is a protein in red blood cells that carries oxygen. Hemoglobin levels (g/dL) were measured in laboratory analyses using patient blood samples.	Baseline, Week 4
Change From Baseline in Serum Ferritin Levels	Ferritin is a blood protein that contains iron. Serum ferritin levels (ng/ml) were measured in laboratory analyses using patient blood samples.	Baseline, Week 4
Change From Baseline in Transferrin Saturation	Transferrin saturation, measured as a percentage, is the value of serum iron divided by the total iron-binding capacity of the available transferrin. Transferrin saturation was measured in laboratory analyses using patient blood samples.	Baseline, Week 4

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Stuart Katz, MD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2017
• Primary Completion (Actual): April 4, 2022
• Study Completion (Actual): April 4, 2022

Study Registration Dates

• First Submitted: July 12, 2017
• First Submitted That Met QC Criteria: July 13, 2017
• First Posted (Actual): July 14, 2017

Study Record Updates

• Last Update Posted (Actual): July 5, 2023
• Last Update Submitted That Met QC Criteria: June 13, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: ferric carboxymaltose; Injectafer; Supplemental Iron
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Anemia; Iron Metabolism Disorders; Heart Failure; Anemia, Iron-Deficiency; Iron Deficiencies
• Other Study ID Numbers: 17-00444

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No