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

NCT ID: NCT03218384

Last Updated: 2023-07-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-07
• Study Completion Date: 2022-04-04

Brief Summary

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.

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.

Conditions

Iron-deficiency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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

Group Type: EXPERIMENTAL

Ferric Carboxymaltose

Intervention Type: DRUG

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.

31P MRS/MRI

Intervention Type: DEVICE

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.

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.

Group Type: ACTIVE_COMPARATOR

Placebo

Intervention Type: DRUG

100 ml of normal saline solution, and administered via volumetric infusion pump over 15 minutes.

31P MRS/MRI

Intervention Type: DEVICE

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.

Interventions

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.

Intervention Type: DRUG

Placebo

100 ml of normal saline solution, and administered via volumetric infusion pump over 15 minutes.

Intervention Type: DRUG

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.

Intervention Type: DEVICE

Other Intervention Names

Injectafer; Saline; 3T Siemens MRI

Eligibility Criteria

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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NYU Langone Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stuart Katz, MD

Role: PRINCIPAL_INVESTIGATOR

NYU Langone Health

Locations

New York University School of Medicine

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

17-00444

Identifier Type: -

Identifier Source: org_study_id